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1.
Journal of Korean Medical Science ; : e20-2022.
Artículo en Inglés | WPRIM | ID: wpr-915538

RESUMEN

Background@#The coronavirus disease 2019 (COVID-19) pandemic caused disruptions to healthcare systems, consequently endangering tuberculosis (TB) control. We investigated delays in TB treatment among notified patients during the first wave of the COVID-19 pandemic in Korea. @*Methods@#We systemically collected and analyzed data from the Korea TB cohort database from January to May 2020. Groups were categorized as ‘before-pandemic’ and ‘during-pandemic’ based on TB notification period. Presentation delay was defined as the period between initial onset of symptoms and the first hospital visit, and healthcare delay as the period between the first hospital visit and anti-TB treatment initiation. A multivariate logistic regression analysis was performed to evaluate factors associated with delays in TB treatment. @*Results@#Proportion of presentation delay > 14 days was not significantly different between two groups (48.3% vs. 43.7%, P = 0.067); however, proportion of healthcare delay > 5 days was significantly higher in the during-pandemic group (48.6% vs. 42.3%, P = 0.012). In multivariate analysis, the during-pandemic group was significantly associated with healthcare delay > 5 days (adjusted odds ratio = 0.884, 95% confidence interval = 0.715–1.094). @*Conclusion@#The COVID-19 pandemic was associated with healthcare delay of > 5 days in Korea. Public health interventions are necessary to minimize the pandemic’s impact on the national TB control project.

2.
Yonsei Medical Journal ; : 789-796, 2020.
Artículo | WPRIM | ID: wpr-833406

RESUMEN

Purpose@#The prevalence of Mycobacterium tuberculosis (M. tb) and the status of M. bovis BCG vaccination may affect host immune responses to M.tb antigens. Understanding of the predominant local M. tb strain and immune signatures induced by its strain-specific antigens may contribute to an improved diagnosis of tuberculosis (TB). The aim of this study was to determine immune responses to M. tb antigen which was identified from the hyper-virulent Beijing/K strain in South Korea. @*Materials and Methods@#Pulmonary TB patients (n=52) and healthy subjects (n=92) including individuals with latent TB infection (n=31) were recruited, and QuantiFERON-TB Gold In-Tube tests were performed. The Beijing/K-antigen specific immune signatures were examined by diluted whole blood assays and multiplex bead arrays in a setting where nationwide BCG vaccination is employed. @*Results@#Statistical analyses demonstrated that three [C-X-C motif chemokine (CXCL10), interleukin (IL)-6, interferon (IFN)-α] of 17 cytokines/chemokines distinguished active cases from healthy controls following stimulation with the Beijing/K-specific antigen. IFN-α also differentiated between active diseases and latent TB infection (p<0.01),and the detection rate of TB was dramatically increased in combination with IL-6 and CXCL10 at the highest levels of specificity (95–100%). @*Conclusion@#Our data indicate that immune signatures to the M. tb Beijing/K-specific antigen can provide useful information for improved TB diagnostics. The antigen may be developed as a diagnostic marker or a vaccine candidate, particularly in regions where the M. tb Beijing/K strain is endemic.

3.
Tuberculosis and Respiratory Diseases ; : 15-22, 2014.
Artículo en Inglés | WPRIM | ID: wpr-15358

RESUMEN

BACKGROUND: Apoptosis plays a role in the development of pleural effusion. Caspase-cleaved cytokeratin 18, a marker for epithelial cell apoptosis, was evaluated in pleural effusion. METHODS: A total of 79 patients with pleural effusion were enrolled. The underlying causes were lung cancer (n=24), parapneumonic effusion (n=15), tuberculous effusion (n=28), and transudates (n=12). The levels of M30, an epitope of caspase-cleaved cytokeratin 18, were measured in blood and pleural fluids using enzyme-linked immunosorbent assay along with routine cellular and biochemical parameters. The expression of M30 was evaluated in the pleural tissues using immunohistochemistry for M30. RESULTS: The M30 levels in pleural fluid were significantly higher in patients with tuberculosis (2,632.1+/-1,467.3 U/mL) than in patients with lung cancer (956.5+/-618.5 U/mL), parapneumonic effusion (689.9+/-413.6 U/mL), and transudates (273.6+/-144.5 U/mL; all p<0.01). The serum levels were not significantly different among the disease groups. Based on receiver operating characteristics analysis, the area under the curve of M30 for differentiating tuberculous pleural effusion from all other effusions was 0.93. In the immunohistochemical analysis of M30, all pathologic types of cancer cells showed moderate to high expression, and the epithelioid cells in granulomas showed high expression in tuberculous pleural tissues. CONCLUSION: Caspase-cleaved cytokeratin 18 was most prominently observed in tuberculous pleural effusion and showed utility as a clinical marker. The main source of M30 was found to be the epithelioid cells of granulomas in tuberculous pleural tissues.


Asunto(s)
Humanos , Apoptosis , Biomarcadores , Citoesqueleto , Ensayo de Inmunoadsorción Enzimática , Células Epiteliales , Células Epitelioides , Exudados y Transudados , Granuloma , Inmunohistoquímica , Queratina-18 , Queratinas , Neoplasias Pulmonares , Derrame Pleural , Curva ROC , Tuberculosis , Tuberculosis Pleural
4.
Tuberculosis and Respiratory Diseases ; : 151-161, 2012.
Artículo en Inglés | WPRIM | ID: wpr-118342

RESUMEN

BACKGROUND: Adequate assessment and control of sedation play crucial roles in the proper performance of mechanical ventilation. METHODS: A total of 30 patients with various pulmonary diseases were prospectively enrolled. The study population was randomized into two groups. The sedation assessment group (SAG) received active protocol-based control of sedation, and in the empiric control group (ECG), the sedation levels were empirically adjusted. Subsequently, daily interruption of sedation (DIS) was conducted in the SAG. RESULTS: In the SAG, the dose of midazolam was significantly reduced by control of sedation (day 1, 1.3+/-0.5 microg/kg/min; day 2, 0.9+/-0.4 microg/kg/min; p<0.01), and was significantly lower than the ECG on day 2 (p<0.01). Likewise, on day 2, sedation levels were significantly lower in the SAG than in the ECG. Significant relationship was found between Ramsay sedation scale and Richmond agitation-sedation scale (RASS; rs=-0.57), Ramsay Sedation Scale and Bispectral Index (BIS; rs=0.77), and RASS and BIS (rs=-0.79). In 10 patients, who didn't require re-sedation after DIS, BIS showed the earliest and most significant changes among the sedation scales. Ventilatory parameters showed significant but less prominent changes, and hemodynamic parameters didn't show significant changes. No seriously adverse events ensued after the implementation of DIS. CONCLUSION: Active assessment and control of sedation significantly reduced the dosage of sedatives in patients receiving mechanical ventilation. DIS, conducted in limited cases, suggested its potential efficacy and tolerability.


Asunto(s)
Humanos , Sedación Consciente , Monitores de Conciencia , Electrocardiografía , Hemodinámica , Hipnóticos y Sedantes , Enfermedades Pulmonares , Midazolam , Estudios Prospectivos , Respiración Artificial , Ventiladores Mecánicos , Pesos y Medidas
5.
Tuberculosis and Respiratory Diseases ; : 36-42, 2011.
Artículo en Coreano | WPRIM | ID: wpr-136345

RESUMEN

BACKGROUND: Adaptive support ventilation (ASV), an automated closed-loop ventilation mode, adapts to the mechanical characteristics of the respiratory system by continuous measurement and adjustment of the respiratory parameters. The adequacy of ASV was evaluated in the patients with acute lung injury (ALI). METHODS: A total of 36 patients (19 normal lungs and 17 ALIs) were enrolled. The patients' breathing patterns and respiratory mechanics parameters were recorded under the passive ventilation using the ASV mode. RESULTS: The ALI patients showed lower tidal volumes and higher respiratory rates (RR) compared to patients with normal lungs (7.1+/-0.9 mL/kg vs. 8.6+/-1.3 mL/kg IBW; 19.7+/-4.8 b/min vs. 14.6+/-4.6 b/min; p<0.05, respectively). The expiratory time constant (RCe) was lower in ALI patients than in those with normal lungs, and the expiratory time/RCe was maintained above 3 in both groups. In all patients, RR was correlated with RCe and peak inspiratory flow (rs=-0.40; rs=0.43; p<0.05, respectively). In ALI patients, significant correlations were found between RR and RCe (rs=-0.76, p<0.01), peak inspiratory flow and RR (rs=-0.53, p<0.05), and RCe and peak inspiratory flow (rs=-0.53, p<0.05). CONCLUSION: ASV was found to operate adequately according to the respiratory mechanical characteristics in the ALI patients. Discrepancies with the ARDS Network recommendations, such as a somewhat higher tidal volume, have yet to be addressed in further studies.


Asunto(s)
Humanos , Lesión Pulmonar Aguda , Automatización , Pulmón , Respiración , Mecánica Respiratoria , Frecuencia Respiratoria , Sistema Respiratorio , Volumen de Ventilación Pulmonar , Ventilación , Lesión Pulmonar Inducida por Ventilación Mecánica , Ventiladores Mecánicos
6.
Tuberculosis and Respiratory Diseases ; : 36-42, 2011.
Artículo en Coreano | WPRIM | ID: wpr-136344

RESUMEN

BACKGROUND: Adaptive support ventilation (ASV), an automated closed-loop ventilation mode, adapts to the mechanical characteristics of the respiratory system by continuous measurement and adjustment of the respiratory parameters. The adequacy of ASV was evaluated in the patients with acute lung injury (ALI). METHODS: A total of 36 patients (19 normal lungs and 17 ALIs) were enrolled. The patients' breathing patterns and respiratory mechanics parameters were recorded under the passive ventilation using the ASV mode. RESULTS: The ALI patients showed lower tidal volumes and higher respiratory rates (RR) compared to patients with normal lungs (7.1+/-0.9 mL/kg vs. 8.6+/-1.3 mL/kg IBW; 19.7+/-4.8 b/min vs. 14.6+/-4.6 b/min; p<0.05, respectively). The expiratory time constant (RCe) was lower in ALI patients than in those with normal lungs, and the expiratory time/RCe was maintained above 3 in both groups. In all patients, RR was correlated with RCe and peak inspiratory flow (rs=-0.40; rs=0.43; p<0.05, respectively). In ALI patients, significant correlations were found between RR and RCe (rs=-0.76, p<0.01), peak inspiratory flow and RR (rs=-0.53, p<0.05), and RCe and peak inspiratory flow (rs=-0.53, p<0.05). CONCLUSION: ASV was found to operate adequately according to the respiratory mechanical characteristics in the ALI patients. Discrepancies with the ARDS Network recommendations, such as a somewhat higher tidal volume, have yet to be addressed in further studies.


Asunto(s)
Humanos , Lesión Pulmonar Aguda , Automatización , Pulmón , Respiración , Mecánica Respiratoria , Frecuencia Respiratoria , Sistema Respiratorio , Volumen de Ventilación Pulmonar , Ventilación , Lesión Pulmonar Inducida por Ventilación Mecánica , Ventiladores Mecánicos
7.
The Korean Journal of Internal Medicine ; : 137-144, 2011.
Artículo en Inglés | WPRIM | ID: wpr-152500

RESUMEN

BACKGROUND/AIMS: We made a systematic review and evaluation of endoscopic cryotherapy of endobronchial tumors, investigating safety and efficacy. METHODS: Qualified studies regarding endoscopic cryotherapy of lung tumors were systemically evaluated using available databases according to predefined criteria. RESULTS: In total, 16 publications were included in the final assessment. A narrative synthesis was performed because a formal meta-analysis was not viable due to the lack of controlled studies and study heterogeneity. Overall success rates for significant recanalization of the obstruction were approximately 80%, although they varied, depending on disease status in the patient population. Complications from the procedure developed in 0-11.1% of cases, most of which were minor and controlled by conservative management. Although limited data were available on comprehensive functional assessment, some studies showed that respiratory symptoms, pulmonary function tests, and performance status were significantly improved. CONCLUSIONS: Endoscopic cryotherapy was found to be a safe and useful procedure in the management of endobronchial tumors although its efficacy and appropriate indications have yet to be determined in well-designed controlled studies.


Asunto(s)
Humanos , Neoplasias de los Bronquios/mortalidad , Broncoscopía/efectos adversos , Criocirugía/efectos adversos , Neoplasias Pulmonares/mortalidad , Estadificación de Neoplasias , Medición de Riesgo , Resultado del Tratamiento
8.
The Korean Journal of Internal Medicine ; : 304-313, 2011.
Artículo en Inglés | WPRIM | ID: wpr-78393

RESUMEN

BACKGROUND/AIMS: Oxidative stress results in protein oxidation and is implicated in carcinogenesis. Sulfiredoxin (Srx) is responsible for the enzymatic reversal of inactivated peroxiredoxin (Prx). Nuclear factor E2-related factor 2 (Nrf2) binds to antioxidant responsive elements and upregulates the expression of Srx and Prx during oxidative stress. We aimed to elucidate the biological functions and potential roles of Srx in lung cancer. METHODS: To study the roles of Srx and Prx III in lung cancer, we compared the protein levels of Nrf2, Prxs, thioredoxin, and Srx in 40 surgically resected human lung cancer tissues using immunoblot and immunohistochemical analyses. Transforming growth factor-beta1, tumor necrosis factor-alpha, and camptothecin treatment were used to examine Prx III inactivation in Mv1Lu mink lung epithelial cells and A549 lung cancer cells. RESULTS: Prx I and Prx III proteins were markedly overexpressed in lung cancer tissues. A significant increase in the oxidized form of a cysteine sulfhydryl at the catalytic site of Prxs was found in carcinogenic lung tissue compared to normal lung tissue. Densitometric analyses of immunoblot data revealed significant Srx expression, which was higher in squamous cell carcinoma tissue (60%, 12/20) than in adenocarcinoma (20%, 4/20). Also, Nrf2 was present in the nuclear compartment of cancer cells. CONCLUSIONS: Srx and Prx III proteins were markedly overexpressed in human squamous cell carcinoma, suggesting that these proteins may play a protective role against oxidative injury and compensate for the high rate of mitochondrial metabolism in lung cancer.


Asunto(s)
Animales , Humanos , Adenocarcinoma/enzimología , Antineoplásicos Fitogénicos/farmacología , Western Blotting , Camptotecina/farmacología , Carcinoma de Células Escamosas/enzimología , Línea Celular Tumoral , Inmunohistoquímica , Neoplasias Pulmonares/enzimología , Visón , Factor 2 Relacionado con NF-E2/metabolismo , Oxidorreductasas actuantes sobre Donantes de Grupos Sulfuro/genética , Peroxiredoxina III/metabolismo , Peroxirredoxinas/metabolismo , Pronóstico , Interferencia de ARN , Especies Reactivas de Oxígeno/metabolismo , Transfección , Factor de Crecimiento Transformador beta1/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Regulación hacia Arriba
9.
Journal of Korean Medical Science ; : 1146-1151, 2010.
Artículo en Inglés | WPRIM | ID: wpr-187255

RESUMEN

It is unclear whether emphysema, regardless of airflow limitation, is a predictive factor associated with survival after lung cancer resection. Therefore, we investigated whether emphysema was a risk factor associated with the outcome after resection for lung cancer. This study enrolled 237 patients with non small cell lung cancer with stage I or II who had surgical removal. Patient outcome was analyzed based on emphysema. Emphysema was found in 43.4% of all patients. Patients with emphysema were predominantly men and smokers, and had a lower body mass index than the patients without emphysema. The patients without emphysema (n=133) survived longer (mean 51.2+/-3.0 vs. 40.6+/-3.1 months, P=0.042) than those with emphysema (n=104). The univariate analysis showed a younger age, higher FEV1/FVC, higher body mass index, cancer stage I, and a lower emphysema score were significant predictors of better survival. The multivariate analysis revealed a younger age, higher body mass index, and cancer stage I were independent parameters associated with better survival, however, emphysema was not. This study suggests that unfavorable outcomes after surgical resection of lung cancer should not be attributed to emphysema itself.


Asunto(s)
Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Edad , Índice de Masa Corporal , Carcinoma de Pulmón de Células no Pequeñas/complicaciones , Enfisema/complicaciones , Neoplasias Pulmonares/complicaciones , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Factores de Riesgo , Fumar , Tasa de Supervivencia
10.
Journal of Lung Cancer ; : 8-12, 2009.
Artículo en Coreano | WPRIM | ID: wpr-54358

RESUMEN

PURPOSE: Concurrent chemoradiotherapy (CCRT) is the standard treatment for locally advanced non-small cell lung cancer (NSCLC). Paclitaxel is an active agent against NSCLC and it has a radiosensitizing effect. We investigated the efficacy and toxicity of weekly paclitaxel administration along with concurrent radiotherapy for treating locally advanced and locally recurrent NSCLC. MATERIALS AND METHODS: Twenty-five previously untreated stage III or locally recurrent NSCLC patients received weekly paclitaxel (60 mg/m2) and concurrent radiotherapy. Chemotherapy was given on days 1, 8, 15 and 22. Concurrent radiotherapy at 1.5 Gy was given twice a day to a total dose of 54 Gy in 3.5 weeks. After the completion of CCRT, consolidation chemotherapy was delivered if possible. RESULTS: The overall response rate was 72% with one complete response and 17 partial responses. The median overall survival was 16 months with a 2 year survival rate and a 5 year survival rate of 38% and 24%, respectively. The rate of grade > 3 radiation pneumonitis was 16% (4 patients) and 2 patients were died from the pneumonitis. The rate of grade 3 radiation esophagitis was 12% (3 patients) and the hematologic toxicities were not significant. CONCLUSION: Weekly paclitaxel with concurrent radiotherapy is effective for treating locally advanced and locally recurrent NSCLC, but radiation pneumonitis is the major toxicity and this is potentially fatal.


Asunto(s)
Humanos , Carcinoma de Pulmón de Células no Pequeñas , Quimioradioterapia , Quimioterapia de Consolidación , Esofagitis , Paclitaxel , Neumonía , Neumonitis por Radiación , Fármacos Sensibilizantes a Radiaciones , Tasa de Supervivencia
11.
The Korean Journal of Internal Medicine ; : 220-226, 2009.
Artículo en Inglés | WPRIM | ID: wpr-150688

RESUMEN

BACKGROUND/AIMS: Peroxiredoxin (Prx) belongs to a ubiquitous family of antioxidant enzymes that regulates many cellular processes through intracellular oxidative signal transduction pathways. Silica-induced lung damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses in alveolar epithelial cells resulting in fibrosis. Therefore, we investigated the role of Prx in the development of lung oxidant injury caused by silicosis, and determined the implication of ROS in that process. METHODS: Lung epithelial cell lines A549 and WI26 were treated with 1% silica for 0, 24, or 48 hours, following pretreatment of the A549 cells with N-acetyl-L-cysteine and diphenylene iodonium and no pretreatment of the WI26 cells. We transfected an HA-ubiquitin construct into the A549 cell line and then analyzed the cells via Western blotting and co-immunoprecipitation. RESULTS: Silica treatment induced cell death in the A549 lung epithelial cell line and selectively degraded Prx I without impairing protein synthesis in the A549 cells, even when the ROS effect was blocked chemically by N-acetyl-L-cysteine. A co-immunoprecipitation study revealed that Prx I did not undergo ubiquitination. CONCLUSIONS: Silica treatment induces a decrease of Prx I expression in lung epithelial cell lines regardless of the presence of ROS. The silica-induced degradation of Prx does not involve the ubiquitin-proteasomal pathway.


Asunto(s)
Humanos , Línea Celular , Células Epiteliales/efectos de los fármacos , Pulmón/química , Peroxirredoxinas/análisis , Isoformas de Proteínas , Especies Reactivas de Oxígeno/metabolismo , Dióxido de Silicio/toxicidad , Ubiquitina/metabolismo
12.
Tuberculosis and Respiratory Diseases ; : 308-313, 2007.
Artículo en Coreano | WPRIM | ID: wpr-22283

RESUMEN

BACKGROUND: The nitric oxide (NO) released by inducible NO synthase (iNOS) plays an important role in the pathophysiology of sepsis. Corticosteroids also play a role in the hemodynamic and inflammatory reactions in sepsis. Both have been shown to have a relationship theoretically, but their correlation and clinical impacts have rarely been evaluated. METHODS: 26 patients with sepsis and 14 healthy controls were enrolled in this study. The initial random plasma total NO and the serum cortisol levels were measured. The same measurements were serially carried out on the 3rd, 5th, and 7th days. RESULTS: The initial total plasma levels of NO and cortisol were higher in the patients with sepsis than in the healthy controls. The total NO levels were higher in patients with severe sepsis than in the those with mild sepsis. There was a correlation between the total NO and cortisol level throughout the study. CONCLUSION: In patients with sepsis, the levels of plasma NO and cortisol were well correlated during the first week of sepsis, which suggests an interrelationship. However, the clinical and pathogenetic implications await further evaluation.


Asunto(s)
Humanos , Corticoesteroides , Hemodinámica , Hidrocortisona , Óxido Nítrico Sintasa , Óxido Nítrico , Plasma , Sepsis , Choque Séptico
13.
Tuberculosis and Respiratory Diseases ; : 356-365, 2006.
Artículo en Coreano | WPRIM | ID: wpr-25903

RESUMEN

BACKGROUND: Corticosteroids are known to be significant prognostic parameters in sepsis. Recently, an absolute and relative insufficiency of the corticosteroids system has often been reported to often develop particularly in severe sepsis. Degree of such an adrenal insufficiency not only has prognostic implications but also can be used to guide corticosteroids replacement therapy. The 24-hour urinary cortisol levels as well as serum cortisol concentrations were measured to assess the clinical significance and their relationship with the other parameters of sepsis, and also evaluated the clinical implications of the relative adrenal insufficiency. METHODS: 26 consecutive patients with sepsis were enrolled. The basal random serum cortisol, ACTH, ADH, lactate levels and 24-hour urinary free cortisol amount were measured. The rapid ACTH (250 microgram) stimulation test was also performed. RESULTS: Basal serum cortisol levels were higher in the non-survivors than in the survivors. The 24-hour urinary free cortisol levels were higher in the patients with severe sepsis than in those without. The serum cortisol levels strongly correlated with the serum ADH and lactate levels. The 24-hour urinary free cortisol levels strongly correlated with the serum cortisol and lactate levels. The fractional changes in the cortisol levels after the rapid ACTH stimulation tests correlated with the serum cortisol, ADH, and lactate levels. CONCLUSION: Both the serum cortisol and 24-hour urinary cortisol were found to be significant prognostic factors in sepsis, and showed a strong correlation with the other parameters. The relative adrenal insufficiency might also be an important clinical parameter.


Asunto(s)
Humanos , Corticoesteroides , Insuficiencia Suprarrenal , Hormona Adrenocorticotrópica , Hidrocortisona , Ácido Láctico , Pronóstico , Sepsis , Sobrevivientes
14.
Infection and Chemotherapy ; : 210-213, 2006.
Artículo en Coreano | WPRIM | ID: wpr-721971

RESUMEN

Streptococcus pneumoniae has been a rare cause of endocarditis in the postantibiotic era. The incidence of pneumococcal endocarditis now accounts for less than 3% of all cases and most often occur in patients with risk factors, especially alcoholism. We report the case of a 68-year-old male with acute infective endocarditis due to Streptococcus pneumoniae. We stressed the low frequency of this agent as a cause of endocarditis and the atypical evolution of this case.


Asunto(s)
Anciano , Humanos , Masculino , Alcoholismo , Bacteriemia , Endocarditis , Endocarditis Bacteriana , Incidencia , Factores de Riesgo , Streptococcus pneumoniae , Streptococcus
15.
Infection and Chemotherapy ; : 210-213, 2006.
Artículo en Coreano | WPRIM | ID: wpr-721466

RESUMEN

Streptococcus pneumoniae has been a rare cause of endocarditis in the postantibiotic era. The incidence of pneumococcal endocarditis now accounts for less than 3% of all cases and most often occur in patients with risk factors, especially alcoholism. We report the case of a 68-year-old male with acute infective endocarditis due to Streptococcus pneumoniae. We stressed the low frequency of this agent as a cause of endocarditis and the atypical evolution of this case.


Asunto(s)
Anciano , Humanos , Masculino , Alcoholismo , Bacteriemia , Endocarditis , Endocarditis Bacteriana , Incidencia , Factores de Riesgo , Streptococcus pneumoniae , Streptococcus
16.
Tuberculosis and Respiratory Diseases ; : 31-42, 2005.
Artículo en Coreano | WPRIM | ID: wpr-145388

RESUMEN

BACKGROUND: Peroxiredoxins (Prxs) are a relatively newly recognized, novel family of peroxidases that reduce H2O2 and alkylhydroperoxide into water and alcohol, respectively. There are 6 known isoforms of Prxs present in human cells. Normally, Prxs exist in a head-to-tail homodimeric state in a reduced form. However, in the presence of excess H2O2, it can be oxidized on its catalytically active cysteine site into inactive oxidized forms. This study surveyed the types of the Prx isoforms present in the pulmonary epithelial, macrophage, endothelial, and other cell lines and observed their response to oxidative stress. METHODS: This study examined the effect of exogenous, excess H2O2 on the Prxs of established cell lines originating from the pulmonary epithelium, macrophages, and other cell lines, which are known to be exposed to high oxygen partial pressures or are believed to be subject to frequent oxidative stress, using non-reducing SDS polyacrylamide electrophoresis (PAGE) and 2 dimensional electrophoresis. RESULT: The addition of excess H2O2 to the culture media of the various cell-lines caused the immediate inactivation of Prxs, as evidenced by their inability to form dimers by a disulfide cross linkage. This was detected as a subsequent shift to its monomeric forms on the non-reducing SDS PAGE. These findings were further confirmed by 2 dimensional electrophoresis and immunoblot analysis by a shift toward a more acidic isoelectric point (pI). However, the subsequent reappearance of the dimeric Prxs with a comparable, corresponding decrease in the monomeric bands was noted on the non-reducing SDS PAGE as early as 30 minutes after the H2O2 treatment suggesting regeneration after oxidation. The regenerated dimers can again be converted to the inactivated form by a repeated H2O2 treatment, indicating that the protein is still catalytically active. The recovery of Prxs to the original dimeric state was not inhibited by a pre-treatment with cycloheximide, nor by a pretreatment with inhibitors of protein synthesis, which suggests that the reappearance of dimers occurs via a regeneration process rather than via the de novo synthesis of the active protein. CONCLUSION: The cells, in general, appeared to be equipped with an established system for regenerating inactivated Prxs, and this system may function as a molecular "on-off switch" in various oxidative signal transduction processes. The same mechanisms might applicable other proteins associated with signal transduction where the active catalytic site cysteines exist.


Asunto(s)
Humanos , Dominio Catalítico , Línea Celular , Medios de Cultivo , Cicloheximida , Cisteína , Electroforesis , Electroforesis en Gel de Poliacrilamida , Epitelio , Punto Isoeléctrico , Macrófagos , Estrés Oxidativo , Oxígeno , Presión Parcial , Peroxidasas , Peroxirredoxinas , Isoformas de Proteínas , Regeneración , Transducción de Señal
17.
Tuberculosis and Respiratory Diseases ; : 142-150, 2005.
Artículo en Coreano | WPRIM | ID: wpr-21517

RESUMEN

BACKGROUND: Continuous growth stimulation by various factors, as well as chronic oxidative stress, may co-exist in many solid tumors, such as lung cancer. A new family of antioxidant proteins, the peroxiredoxins (Prxs), have been implicated in the regulation of many cellular processes, including cell proliferation, differentiation and apoptosis. However, a real pathophysiological significance of Prx proteins, especially in lung disease, has not been sufficiently defined. Therefore, this study was conducted to investigate the distribution and expression of various Prx isoforms in lung cancer and other pulmonary conditions. METHOD: Patients diagnosed with lung cancer, and who underwent surgery at the Ajou Medical Center, were enrolled. The expressions of Prxs, Thioredoxin (Trx) and Thioredoxin reductase (TR) were analyzed using proteomic techniques and the subcellular localization of Prx proteins was studied using immunohistochemistry on normal mouse lung tissue. RESULT: Immunohistochemical staining has shown the isoforms of Prx I, II, III and V are predominantly expressed in bronchial and alveolar lining epithelia, as well as in the alveolar macrophages of the normal mouse lung. The isoforms of Prx I and III, and thioredoxin were also found to be over-expressed in the lung cancer tissues compared to their paired normal lung controls. There was also an increased amount of the oxidized form of Prx I, as well as a putative truncated form of Prx III, in the lung cancer samples when analyzed using 2-dimensional electrophoresis. In addition, a 43 kDa intermediate molecular weight protein band, and other high molecular weight bands of over 20 kDa, recognized by the anti-Prx I antibody, were present in the tissue extracts of lung cancer patients on 1-Dimensional electrophoresis, which require further investigation. CONCLUSION: The over-expressions of Prx I and III, and Trx in human lung cancer tissue, as well as their possible chaperoning function, may represent an attempt by tumor cells to adjust to their microenvironment in a manner advantageous to their survival and proliferation, while maintaining their malignant potential.


Asunto(s)
Animales , Humanos , Ratones , Apoptosis , Proliferación Celular , Electroforesis , Inmunohistoquímica , Enfermedades Pulmonares , Neoplasias Pulmonares , Pulmón , Macrófagos Alveolares , Peso Molecular , Estrés Oxidativo , Peroxirredoxinas , Isoformas de Proteínas , Reductasa de Tiorredoxina-Disulfuro , Tiorredoxinas , Extractos de Tejidos
18.
Tuberculosis and Respiratory Diseases ; : 594-598, 2004.
Artículo en Coreano | WPRIM | ID: wpr-95162

RESUMEN

Signet ring cell carcinoma of lung is an unique variant of mucin producing adenocarcinoma which is characterized by abundant intracellular mucin accumulation. Only a few cases of primary signet ring cell carcinoma of lung have been reported in the world wide literature. And we have, recently experienced one case of primary signet ring cell carcinoma of lung. A 55 years old man was evaluated for paralysis of lower extremities and was found to have lung cancer in the left upper and lower lobe with pleural, multiple spinal, bone and liver metastases. Signet ring tumor cells were revealed by cytologic examination of pleural fluids. And there were no evidence of signet ring cell carcinoma of other organs. Primary signet ring cell carcinoma of lung seems to have an aggressive behavior and therapeutic modalities could be different from those for signet ring cell carcinomas from other organs. Therefore it is important to separate primary signet ring cell adenocarcinoma of lung from metastatic tumors.


Asunto(s)
Humanos , Persona de Mediana Edad , Adenocarcinoma , Carcinoma de Células en Anillo de Sello , Hígado , Extremidad Inferior , Neoplasias Pulmonares , Pulmón , Mucinas , Metástasis de la Neoplasia , Parálisis
19.
Tuberculosis and Respiratory Diseases ; : 506-515, 2003.
Artículo en Coreano | WPRIM | ID: wpr-32117

RESUMEN

BACKGROUND: A decreased level of serum arginine vasopressin(AVP) and an increased sensitivity to an exogenous AVP is expected in patients with septic shock who often require a high infusion rate of catecholamines. The goal of the study was to determine whether an exogenous AVP infusion to the patients with septic shock would achieve a significant decrement in infusion rate of catecholamine vasopressors while maintaining hemodynamic stability and adequate urine output. METHODS: Eight patients with septic shock who require a high infusion rate of norepinephrine had received a trial of 4-hour AVP infusion with simultaneous titration of norepinephrine. Hemodynamic parameters and urine output were monitored during the AVP infusion and the monitoring continued up to 4 hours after the AVP infusion had stopped. RESULTS: Mean arterial pressure showed no significant changes during the study period(p=0.197). Norepinephrine infusion rate significantly decreased with concurrent AVP administration(p=0.001). However, beneficial effects had disappeared after the AVP infusion was stopped. In addition, hourly urine output showed no significant changes throughout the trials(p=0.093). CONCLUSION: Concurrent AVP infusion achieved the catecholamine vasopressor sparing effect in the septic shock patients, but there was no evidence of the improvement of renal function. Further study may be indicated to determine whether AVP infusion would provide an organ-protective effect to the septic shock patients.


Asunto(s)
Humanos , Arginina , Presión Arterial , Catecolaminas , Hemodinámica , Norepinefrina , Choque Séptico
20.
Tuberculosis and Respiratory Diseases ; : 623-630, 2003.
Artículo en Coreano | WPRIM | ID: wpr-81367

RESUMEN

Microscopic polyangiitis is a systemic small-vessel vasculitis that is primarily associated with necrotizing glomerulonephritis and pulmonary capillaritis. Lung involvement is characterized by a diffuse alveolar hemorrhage. However, rarely central nervous system involvement has been reported to be occurred with the microscopic polyangiitis. Relapse of microscopic polyangiitis are reported to be more frequent than those of polyarteritis nodosa, often after a reduction or discontinuation of the therapy. We would like to report two patients with microscopic polyangiitis. One presented with clinical manifestations of both lung and central nervous system involvements and the other was a case of recurrence during steroid tapering following the steroid pulse therapy.


Asunto(s)
Humanos , Anticuerpos Anticitoplasma de Neutrófilos , Sistema Nervioso Central , Glomerulonefritis , Hemorragia , Pulmón , Poliangitis Microscópica , Poliarteritis Nudosa , Recurrencia , Vasculitis , Vasculitis del Sistema Nervioso Central
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