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Itaru Ishida

Publications and source records attributed to Itaru Ishida.

5 recordsLinked to original sources

Effects of rewarming on nuclear factor-kappaB and interleukin 8 expression in cold-preserved alveolar epithelial cells.

BACKGROUND: Nuclear factor-kappaB (NF-kappaB) and interleukin (IL)-8 play important roles in the pathophysiology of acute lung injury after lung transplantation. Because alveolar epithelium is one of the most important sites at which IL-8 production takes place after reperfusion of donor lungs, we examined the effects of cold/rewarming on NF-kappaB and IL-8 expression in alveolar epithelial cells. METHODS: A549 cells were preserved at 4 degrees C for 5 hr and then rewarmed for up to 20 hr. NF-kappaB was analyzed by electrophoretic mobility shift assay. IL-8 mRNA expression was examined by reverse transcription-polymerase chain reaction. IL-8 concentration in the cell culture medium after rewarming was measured by enzyme-linked immunosorbent assay. RESULTS: NF-kappaB was increased in the nuclear extracts as early as 30 min after rewarming. There was a marked increase in the IL-8 mRNA expression at 1 and 3 hr after rewarming. IL-8 concentration in the cell culture medium was progressively increased during 20 hr following rewarming. The cell culture medium inhibited apoptosis of neutrophils significantly. The cold/rewarming-induced IL-8 production was reduced to approximately 50% by introducing an antisense oligonucleotide for the p65 subunit of NF-kappaB and by treatment with N-acetyl-leucinyl-leucinyl-norleucinal and pyrrolidine dithiocarbamate. The effect of dexamethasone treatment was dose dependent (reduced to approximately 30% at 10-5 M dexamethasone). CONCLUSIONS: Our results indicate that rewarming of cold-preserved alveolar epithelial cells itself may be an important initiator of the inflammatory cascades, including NF-kappaB activation and IL-8 release. Inhibition of NF-kappaB would be worth trying to control unnecessary IL-8 production and the inflammatory response in the donor lungs.

Apoptosis↗

A prospective evaluation of transbronchial ultrasonography for assessment of depth of invasion in early bronchogenic squamous cell carcinoma.

In order to determine the appropriate treatment modality for roentgenographically occult bronchogenic squamous cell carcinoma (ROSCC), it is essential to evaluate the depth of invasion, because ROSCC invading beyond the cartilaginous layer cannot be effectively treated by photodynamic therapy (PDT) due to spread of disease. Transtracheal endoscopic ultrasonography (TUS) was useful for predicting the depth of invasion in some ROSCCs. In order to assess the actual significance of TUS as a diagnostic tool for predicting the depth of carcinoma invasion, we have conducted a prospective trial with 22 lesions of ROSCCs. We ultrasonographically classified the degree of the depth of invasion into two groups; A: "invasion does not reach cartilaginous layer" and B: "invasion involves cartilaginous layer". Then the patients were treated by irradiation, PDT, or surgical resection. Pathological findings were also classified into A or B. In order to calculate the sensitivity for evaluating the depth of invasion by TUS, the cases without any tumor and/or malignant cells after PDT were regarded as pathological A. In the evaluation of the depth of carcinoma invasion staying inside the cartilaginous layer, the sensitivity and the positive predictive value were 85.7%, the specificity was 66.7%, and the accuracy was 80.0%. With TUS, preoperative evaluation of the depth of invasion would be more accurate, and the decision of treatment modality would be more appropriate, compared with the conventional bronchoscopic observation alone.

Aged↗

Hypoxia diminishes toll-like receptor 4 expression through reactive oxygen species generated by mitochondria in endothelial cells.

Hypoxia and inflammation often occur simultaneously due to prevention of adequate gas exchange. Understanding the influence of hypoxia on the inflammatory response is important because hypoxia directly regulates expression of many genes, including those regulating inflammation, and plays a role in modulating the resolution of an inflammatory response. LPS is a major mediator of cellular injury and inflammation that induces its effects through Toll-like receptor 4 (TLR4). The aim of this study was to evaluate the effect of hypoxia on TLR4 expression. Hypoxia decreased TLR4 expression on cultured endothelial cells. Furthermore, LPS-induced ICAM-1 up-regulation was decreased by hypoxia. Because reactive oxygen species (ROS) generated from mitochondria are one of the signaling molecules induced by hypoxia, the role of ROS in hypoxia-induced TLR4 down-regulation was evaluated. Our data showed that hypoxia increased ROS generation and that hypoxia-induced TLR4 down-regulation was inhibited by myxothiazol, a mitochondrial site III electron transport inhibitor. Hypoxia also inhibited AP-1 translocation. Since the TLR4 promoter has a binding site for AP-1, hypoxia-induced TLR4 down-regulation may be due to an ROS-mediated decrease in AP-1-binding activity. We conclude that hypoxia decreases TLR4 expression in endothelial cells and that this change is mediated by mitochondrial ROS leading to attenuation of AP-1 transcriptional activity.

Cell Hypoxia↗

Roentgenographically occult bronchogenic squamous cell carcinoma involving mediastinal lymph nodes after removal of initial lesion by the diagnostic examination.

A 69-year-old male was suspected of having lung cancer by sputum cytology and diagnosed as roentgenographically occult squamous cell carcinoma (ROSCC) at the spur of left B(1+2)/B(3). However, after the first bronchoscopy, no suspicious lesion was detected by any examinations. Therefore, we considered that cancer cells had been removed completely by the initial examination, and the patient was followed up by sputum cytology, chest roentgenogram, and bronchoscopy. Sixteen months later from the initial examination, bronchoscopy was performed for follow-up. The bronchoscopic findings showed the elevation of the surface of left B(1+2) a+b, but the cytologic specimen by brushing toward B(1+2) a+b showed negative findings. However, the lesion had developed to polypoid-shaped tumor and obstructed B(1+2) a+b after the next 6 months. The tumor was diagnosed as squamous cell carcinoma, and hilar and mediastinal nodal involvement was suspected on chest computed tomography. The standard thoracotomy was performed and the pathological results showed positive for nodal involvement on hilus and mediastinum. The tumor is considered to arise from the residual cancer cells of initially detected ROSCC. In conclusion, although some ROSCCs regress by the diagnostic examinations, it is important to detect the recurrence of residual cancer cells as early as possible by intensive follow-up.

Aged↗

Computed tomographic image comparison between mediastinal and lung windows provides possible prognostic information in patients with small peripheral lung adenocarcinoma.

OBJECTIVES: The purpose of this study was to determine whether the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor of small peripheral lung adenocarcinoma. METHODS: We studied the computed tomographic images of 143 patients with primary peripheral lung adenocarcinoma of 30 mm or less in maximum diameter. Two groups were categorized according to the tumor's ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image (tumor's area in the mediastinal computed tomographic image/tumor's area in lung computed tomographic image x 100%), both faint density-type (<50%) and solid-type images (>/=50%). Clinical factors and prognoses of the 2 groups were analyzed. RESULTS: There were 58 patients with the solid-type tumor image and 85 patients with the faint density-type tumor image. The number of patients with tumor size of less than 20 mm in the faint density-type tumor group (n = 30) was significantly higher than that in the solid-type tumor group (n = 8, P =.008). The 5-year survival of patients with faint density-type tumors was 74.1%, whereas that in patients with solid-type tumors was 54.2% (P =.013). Furthermore, the survival curve of patients with the solid-type computed tomographic image combined with ground-glass opacity was similar to that of patients with the faint density-type image. Multivariate analysis revealed the prognostic influence of the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image on survival (P =.029, relative risk = 0.48) and showed to be of second highest influence after the N factor. CONCLUSIONS: It is suggested that the ratio of the area of the mediastinal computed tomographic image to that of the lung computed tomographic image can be a prognostic factor in patients with small peripheral lung adenocarcinoma.

Adenocarcinoma↗