Noritaka Isowa

Protection against reperfusion-induced arrhythmias by human thioredoxin.

Adult T-cell leukemia-derived factor (ADF), identified in the supernatant of adult T-cell leukemia (ATL) cell culture, is a human homologue of thioredoxin and consists of 104 amino acids; it has two redox-active half-cysteine residues in an exposed active center. Human thioredoxin has many biological activities, including growth promotion, cell activation, and a catalase-like radical scavenging activity. We examined the protective effect of human thioredoxin (h-thioredoxin) against reperfusion-induced arrhythmias in an isolated rat heart model with 10-min regional ischemia followed by 30-min reperfusion. Male Wistar rats were assigned to six groups: a control, a superoxide dismutase (SOD 8 x 10(4) IU/L), and a catalase group (1 x 10(6) IU/L), and three groups treated with h-thioredoxin [approximately .01 microM (TRX-I group), approximately 0.1 microM (TRX-II group), and approximately 1 microM (TRX-III group)]. In the early reperfusion period, h-thioredoxin reduced the incidence of ventricular fibrillation (VF) to 8% in the TRX-II group (p < 0.01) from the control value of 75%. SOD and catalase reduced the incidence of VF to 43 and 33%, respectively (NS). During the entire reperfusion period, the incidence of VF in the SOD group was 79%, as compared to 83% in the control group. In the catalase and TRX-II groups, the incidence of VF was significantly reduced to 42 and 25%, respectively. These findings indicate that SOD failed to protect against the reperfusion-induced arrhythmias. h-Thioredoxin exerted a protective effect against these arrhythmias; a concentration of approximately 0.1 micro was the most effective.

Amelioration of ischemia-reperfusion injury by human thioredoxin in rabbit lung

Human thioredoxin is a polypeptide with thiol groups, possessing reducing activity, which is proved to have the ability to reduce active oxygens. This study evaluated the effect of human thioredoxin on the ischemia-reperfusion lung injury and the roles of human thioredoxin on active oxygens by chemiluminescence examination. The left hilum of the lung of Japanese white rabbits was occluded for 110 minutes and then reperfused for 90 minutes. Ten, 30, 60, and 90 minutes after reperfusion the right hilum was occluded for 5 minutes and the pulmonary functions of the left lung were examined. The animals were divided into four groups, three ischemia groups and a sham group (without occlusion; n = 6). The ischemia groups received human thioredoxin, 60 mg/kg (n = 10), N-acetylcysteine, 150 mg/kg (n = 7), or saline solution (control, n = 10) during reperfusion. Three rabbits in the human thioredoxin group and the control group were used to measure active oxygens with a cypridina luciferin analog. An additional group of reperfused lungs (n = 3) that were given superoxide dismutase after 110 minutes of ischemia was established to identify chemiluminescence examination. Compared with the sham group, reperfusion after 110 minutes of ischemia produced a significant lung injury in the control group. Among the ischemia groups, the human thioredoxin group showed significantly higher arterial oxygen tension at 30, 60, and 90 minutes after reperfusion than the control group, although there was no significant difference between the N-acetylcysteine and control groups. Histologically, intraalveolar exudation, interstitial thickening, and cellular infiltration were seen in the control group, whereas in the thioredoxin group alveolar structure was well preserved. In the measurement of active oxygens the chemiluminescence in the human thioredoxin group was less than that in the control group and as little as that in the group administered superoxide dismutase. We concluded human thioredoxin attenuated ischemia-reperfusion injury by involving active oxygens in rabbit lungs.

Successful thoracoscopic debridement of descending necrotizing mediastinitis.

Descending necrotizing mediastinitis results from odontogenic, deep neck infection that spreads along fascial planes into the mediastinum. Although the optimal surgical approach remains controversial, nearly half of the cases require mediastinal debridement by thoracotomy. We report a case of successful thoracoscopic debridement for descending necrotizing mediastinitis due to odontogenic infection that failed to be drained by transcervical approach. Because of less invasiveness as compared with standard thoracotomy, the thoracoscopic approach should be used as early as possible in case of unsuccessful transcervical approach.

Human thioredoxin attenuates hypoxia-reoxygenation injury of murine endothelial cells in a thiol-free condition.

The adult T cell leukemia‐derived factor (ADF), or human thioredoxin (hTRX), has a radical scavenging effect similar to that of N‐acetyl cysteine (NAC). We have recently shown that ADF/hTRX protects the lung and the heart from ischemia‐reperfusion induced injury. To elucidate mechanisms of the protective effect, a hypoxia‐reoxygenation (H‐R) injury model was developed using a murine endothelial cell line, cultured in a thiol‐free medium. In this condition, cells became much more vulnerable to H‐R injury. The viability of cells decreased significantly after 1 h of hypoxic incubation followed by 1 h of reoxygenation. The injury was reduced by ADF/hTRX (100 μM) or NAC (10 mM). These two agents also demonstrated an additive protective effect. When cells were cultured in thiol‐free medium for 2 h in a normoxic condition, intracellular hydrogen peroxide production was increased, which was associated with a decrease in glutathione level. NAC (10 mM) attenuated these changes whereas ADF/hTRX (100 μM) did not. These results suggest that although both ADF/hTRX and NAC protected cells from H‐R injury, the underlying mechanisms are different. Because the cytoprotective effect of ADF/hTRX occurs in the thiol‐free condition, it must be mediated via a novel mechanism other than enhancing thiol uptake. The additive cytoprotective effect between ADF/hTRX and NAC suggests that we should combine these two agents clinically. J. Cell. Physiol. 182:33–40, 2000.

Lung adenocarcinomas with micropapillary components

PurposeMicropapillary adenocarcinoma is becoming increasingly recognized as a prognostically important histological subtype of carcinoma in various organs. This report presents the clinicopathological findings of lung adenocarcinomas with micropapillary components.MethodsA total of 15 patients with micropapillary components were selected between April 2005 and December 2008. The results of their clinical presentation, metastasis to lymph nodes, pleural invasion, pathological stage, and clinical outcomes were evaluated.ResultsIn all, 12 patients underwent a lobectomy or bilobectomy with a regional lymph node dissection; 8 showed metastases to the regional lymph nodes at the time of the operation. Altogether, 14 of 15 cases showed lymphovascular invasion; 10 cases were up-staged after the operation because of lymph node metastases or pleural invasion. The duration of follow-up ranged from 1 to 42 months (median 16 months). Seven patients are alive without disease, whereas seven are alive with disease and one patient died of disease.ConclusionThese results suggest that the micropapillary components are a manifestation of aggressive behavior, as shown by the frequent lymph node metastases and pleural invasion. Surgeons should search more carefully for metastases and conduct a closer follow-up on these patients when this feature is present with lung adenocarcinoma.

Primary malignant melanoma of the lung with rapid progression

This report presents a case of primary malignant melanoma of the lung with rapid progression in a 68-year-old man. During a regular checkup, a chest roentgenogram revealed an abnormal shadow in the left lower lung field. Computed tomography (CT) of the chest revealed an ill-defined tumor shadow measuring 4 × 3 cm in the left upper lobe. A CT-guided lung biopsy suggested a large-cell carcinoma, and left upper lobectomy was performed. Histopathologically, the tumor was comprised of malignant epithelial tumor cells with large amounts of acidophilic cytoplasm and prominent nuclei. A dark brown pigment was observed in the tumor cells. Immunohistochemical staining was positive for S-100 protein and HMB45; staining for cytokeratin, CAM5.2, and chromogranin was negative. The final diagnosis was malignant melanoma of the lung. Two months later, multiple brain metastases developed, and he died of the disease 6 months after the surgery.

Bilateral multiple sclerosing hemangiomas of the lung

This report presents a case of bilateral multiple sclerosing hemangiomas of the lung in a 73-year-old woman. A computed tomography (CT) scan of the chest showed a total of three well-defined small nodules in the right and left lower lobes of the lung. Because malignant metastatic lung tumors were highly suspected, a wedge resection of the left lower lobe was performed to obtain a definitive diagnosis. Histopathologically, two tumors of the left lower lobe were composed of epithelial-like cuboidal cells covering the surface of papillary protrusions and sheets of round to polygonal cells underneath the epithelial-like cells. The final diagnosis was that both tumors were sclerosing hemangiomas. After surgery the residual lesion of the right lower lobe was carefully followed by chest CT. The size of the right lung nodule did not change over the course of 9 years, and no new lesion has emerged.

Pulmonary intestinal-type adenocarcinoma

We report a rare case of pulmonary intestinal-type adenocarcinoma in a 69-year-old man. A computed tomographic scan of the chest and positron emission tomography revealed a well-defined nodule measuring 2.5 cmx2.5 cm in the right lower lobe with high (18)F-fluorodeoxyglucose accumulation. Furthermore, sputum cytology tested positive for adenocarcinoma. Right lower lobectomy and systemic lymph node dissection were performed by video-assisted thoracic surgery (VATS). Histopathologically, the tumor was composed mainly of tall columnar cells with similarity to intestinal epithelia and colorectal carcinoma. Immunohistochemical staining was positive for cytokeratin 7 (CK7) and thyroid transcription factor-1 (TTF-1), whereas staining for cytokeratin 20 (CK20) was negative. The final diagnosis was primary pulmonary intestinal-type adenocarcinoma.

The maximum standardized 18F-fluorodeoxyglucose uptake on positron emission tomography predicts lymph node metastasis and invasiveness in clinical stage IA non-small cell lung cancer

In patients with clinical stage IA non-small cell lung cancer (NSCLC), we investigated whether the maximum standardized uptake value (SUVmax) of 18F-fluorodeoxyglucose (FDG) by the tumor correlated with lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells, and pleural invasion. From April 2005 to November 2008, 58 patients underwent a lobectomy with systematic hilar and mediastinal lymph node dissection for clinical stage IA NSCLC. All patients had integrated FDG-positron emission tomography (PET)/computed tomography (CT) performed in our center as part of the preoperative workup within one month of resection. The relationships between the SUVmax and pathologic results of lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells, and pleural invasion were examined. Compared with tumors with an SUVmax < or = 2.0, tumors with an SUVmax>2.0 had more frequent lymph node metastasis, intratumoral lymphatic and vascular invasion of tumor cells and pleural invasion (all P<0.05). Our results suggest that in patients with clinical stage IA NSCLC, SUVmax is an important predictor of tumor invasiveness.

Pulmonary resection for metastases from colorectal carcinoma.

A pulmonary resection of metastatic colorectal carcinoma is an accepted method of treatment. The purpose of this study was to confirm the role of resections for pulmonary metastases from colorectal carcinoma, and to determine the clinical course, outcome, and prognostic factors after surgery. A retrospective analysis was conducted of the records of all patients with pulmonary metastases from colorectal carcinoma who underwent a surgical resection between 1995 and 2008, at a single surgical center. The overall 5-year survival rate was 74%. Multivariate Cox analysis demonstrated that the number of pulmonary metastases (HR: 9.40, 95% confidence interval (CI): 1.08-82.2, P=0.0428) and prethoracotomy carcinoembryonic antigen (CEA) level (HR: 9.79, 95% CI: 1.11-86.8, P=0.0404) were statistically significant predictors of survival after the first pulmonary metastasectomy. In addition, a second resection for recurrent metastases was performed in eight patients, and a third resection was done in one patient. There were no major postoperative complications among the patients who underwent second or third resections. Pulmonary resections are considered to be a safe and effective treatment in selective patients.