Biomedical subjects

Hiroyoshi Tsubochi

Publications and source records attributed to Hiroyoshi Tsubochi.

10 recordsLinked to original sources

PubMed2006

Preoperative chemotherapy for cStage III-pN0 patients with non-small cell lung cancer.

OBJECTIVES: Survival benefits with preoperative chemotherapy for non-small cell lung cancer (NSCLC) remain controversial. Preoperative chemotherapy may act on micrometastasis but not lymph node metastasis. To clarify the role of induction chemotherapy for control of micrometastasis, we reviewed and compared 5-year follow-ups of clinical stage III but pathologically-proven node-negative NSCLC patients after complete resection with or without preoperative chemotherapy. METHODS: We reviewed 148 consecutive patients who underwent anatomical lung resection and mediastinal nodal dissection for pathologically-proven node-negative NSCLC at our hospital between 1994 and 1999. Fifty-six patients were preoperatively diagnosed as stage III: 26 received platinum-based chemotherapy prior to surgery (PCT group) and 30 underwent surgery without any prior chemotherapy (PRS group). RESULTS: The 5-year survival rate for clinical stage I/II and pathological node-negative patients was 74.9%; for clinical stage III, but for pathological node-negative patients it was 92.3% in the PCT and 63.3% in the PRS groups. The survival benefit of preoperative chemotherapy was significant for clinical stage II patients without node involvement. CONCLUSION: Preoperative chemotherapy may provide survival benefits for node-negative NSCLC patients.

Aged↗

PubMed2006

Plastron-trapdoor technique for direct-vision sternal re-entry.

Repeat median sternotomy does not allow good access for retrosternal re-entry. Conversely, by using the plastron-trapdoor technique, which we describe in this report, the retrosternal tissues are dissected from the body of the sternum under direct vision, thus allowing relatively safe and wide exposure for retrosternal re-entry.

Aged↗

PubMed2006

Predictors of postoperative complications after radical resection for pulmonary aspergillosis.

OBJECTIVE: Although surgery has proven to be the best treatment for pulmonary aspergillosis, with the highest chance of achieving complete remission, it is difficult to determine the surgical indications for this disease because of the high incidence of postoperative complications. We conducted this study to identify some predictors of postoperative complications, in an attempt to reduce the morbidity rate. METHODS: We retrospectively analyzed the medical records of 31 patients (18 men, 13 women; median age 53 years) who underwent radical resection for pulmonary aspergillosis between 1976 and 2004. The clinical manifestations, surgical procedures, and postoperative complications were reviewed to clarify the predictors of postoperative complications. RESULTS: The morbidity rate associated with major complications such as intrapleural bleeding, bronchopleural fistula, and empyema, resulting in further surgery, was 19%. Univariate analysis revealed the predictors of major complications to be sex, severe preoperative symptoms, and extensive pulmonary resection. Multivariate analyses also indicated that preoperative symptom severity was an independent predictor of major complications. CONCLUSIONS: Pulmonary aspergillosis should be resected before the symptoms become too severe if the patient is a surgical candidate.

Adult↗

PubMed2006

Combined analysis of cyclooxygenase-2 expression with p53 and Ki-67 in nonsmall cell lung cancer.

BACKGROUND: Cyclooxygenase-2 (COX-2) is known to play a role in carcinogenesis and tumor progression. The aim of this study was to evaluate the relationship between COX-2 expression and clinicopathologic features, and to define the importance of COX-2 expression alone and in combination with p53 and Ki-67 expression in the clinical outcome of NSCLC. METHODS: A total of 219 patients with stage I-IIIB nonsmall cell lung cancer (NSCLC) who previously underwent surgery were analyzed in this study. The COX-2 expression was evaluated by means of immunohistochemistry; p53 and Ki-67 immunoreactivity were also studied. RESULTS: The COX-2 expression was observed in 137 patients (63%) and was significantly associated with lymph node metastasis and the histological grade of those with adenocarcinoma (p = 0.02 and 0.04, respectively). Kaplan-Meier analyses revealed that COX-2 expression was correlated with poor survival (p = 0.005), whereas multivariate survival analysis did not reveal COX-2 expression to be an independent prognostic factor. When the patients were stratified according to gender, age, tumor histology, and disease stage, COX-2 expression was significantly associated with unfavorable prognosis in males, younger patients (< or = 65 years), and those with adenocarcinoma and stage I tumors. The prognosis of patients with tumors negative for both COX-2 and p53 expression was significantly favorable, whereas those with tumors positive for COX-2 expression and with a high Ki-67 labeling index had a significantly unfavorable prognosis. CONCLUSIONS: These findings indicate that combined immunohistochemical analysis of COX-2 with p53 and Ki-67 can be useful for identifying the prognosis of NSCLC patients.

Adult↗

PubMed2005

Successfully treated lingual tonsillar metastasis from bronchial adenocarcinoma.

Tonsillar metastasis from neoplasms, including lung cancer, are extremely rare, and the prognosis for patients with tonsillar metastases is rather poor. We herein describe a case of long-term survival following radiation for lingual tonsillar metastasis from a bronchial adenocarcinoma. A 39-year-old male was diagnosed with adenocarcinoma of the right lung and was surgically treated. Four months after surgery, a mass arising from the lingual tonsil was noted at the root of the tongue and was pathologically diagnosed as metastasis from lung cancer. In addition, a computed tomography scan revealed a jugular lymphadenopathy, which was considered to be a metastasis from the tonsillar tumor. The tonsillar mass and jugular lymphadenopathy disappeared after external radiotherapy (50 Gy). The patient is alive without recurrence more than 8 years after treatment for tonsillar metastasis. This is the first report of successfully treated tonsillar metastasis from a malignant tumor.

Adenocarcinoma↗

PubMed2005

Inflammatory mediators down-regulate 11beta-hydroxysteroid dehydrogenase type 2 in a human lung epithelial cell line BEAS-2B and the rat lung.

In the lung, anti-inflammatory actions of glucocorticoids would be determined by 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), the microsomal enzyme responsible for the breakdown of bio-active glucocorticoids. However, regulation of 11beta-HSD2 under inflammatory conditions such as acute lung injury is not well understood. In the present study, we examined whether inflammatory substances would influence the activity and mRNA expression of 11beta-HSD2 in the lung. In a human bronchial epithelial cell line BEAS-2B, endotoxin inhibited 11beta-HSD2 enzyme activity in a dose-dependent manner over 48 h with a significant decrease in the mRNA expression. Likewise, tumor necrosis factor (TNF)-alpha inhibited both activity and mRNA expression of 11beta-HSD2. The TNF-alpha-dependent decrease in the enzyme activity was completely blocked by anti-TNF-alpha antibody, while antibody alone showed no significant influence on the enzyme activity. An nitric oxide donor (NO) sodium nitropusside or a cGMP analog 8-br-cGMP caused moderate but significant decreases in both activity and mRNA expression of 11beta-HSD2. Importantly, treatment of rats with endotoxin significantly decreased both activity and mRNA expression of 11beta-HSD2 in the lung tissue. We conclude that lung inflammation reduces local glucocorticoid breakdown and augments glucocorticoid action in the lung by down-regulating 11beta-HSD2 via multiple mechanisms.

11-beta-Hydroxysteroid Dehydrogenases↗

PubMed2003

Early changes in alveolar fluid clearance by nitric oxide after endotoxin instillation in rats.

Alveolar fluid clearance may be inhibited and/or stimulated under pathologic conditions. We examined the early change of alveolar fluid clearance after endotoxin instillation in adult rats. We employed electron paramagnetic resonance nitric oxide (NO) trapping technique with iron complex with N,N-diethyldithiocarbamate as an NO trapping agent. We found that lung NO signals reached the highest magnitude by 6 hours after endotoxin instillation. NO production was accompanied by increases in lung cyclic guanosine monophosphate levels. Alveolar fluid clearance decreased significantly 6 hours after the administration of the endotoxin and increased further at 24 hours. These changes were shown to be related to the function of amiloride-sensitive sodium ion channels. Treatment with gadolinium chloride and aminoguanidine significantly decreased lung NO and cyclic guanosine monophosphate levels and completely ameliorated the decrease in alveolar fluid clearance. In addition, the increase in alveolar fluid clearance at 24 hours returned to normal levels after treatment with gadolinium chloride and aminoguanidine. We found immunoreactive inducible nitric oxide synthase to be abundantly expressed in the cytoplasm of alveolar macrophages. Our results suggest that alveolar endotoxin inhibits alveolar fluid clearance at 6 hours by NO. NO is produced via inducible NO synthase in endotoxin-stimulated alveolar macrophages and was also shown to increase alveolar fluid clearance at 24 hours.

Animals↗

PubMed2003

Increased expression of 11 beta-hydroxysteroid dehydrogenase type 2 in the lungs of patients with acute respiratory distress syndrome.

We examined the immunohistochemical distribution of 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2), the enzyme responsible for the conversion of bioactive glucocorticoids to their receptor-inactive forms, in lung tissue obtained at autopsy from 14 patients who had died due to acute respiratory distress syndrome (ARDS). We found positive immunoreactivity for 11 beta-HSD2 in 13 cases. The cells expressing 11 beta-HSD2 in the alveolar wall were positive for surfactant apoprotein-A as well as cytokeratin. Immunoreactivity for 11 beta-HSD2 was also detected in the CD68+ cells, which were found in the alveolar spaces. All patients had been treated with glucocorticoids for ARDS and/or the underlying diseases. There was no statistically significant correlation between the use of glucocorticoids and 11 beta-HSD2 immunoreactivity in the alveolar wall (P = 0.0729). However, expression of grade + + was found in three out of five patients who received dexamethasone pulse therapy at relatively large doses, as well as in three other patients treated with prednisolone for a long period of time for the underlying disease. An increase in the expression of 11 beta-HSD2 may result in faster glucocorticoid breakdown in lung cells in patients with ARDS. Impaired glucocorticoid availability in the lungs of such patients may explain, in part, the fact that glucocorticoid therapy does not always rescue patients with ARDS.

11-beta-Hydroxysteroid Dehydrogenase Type 2↗

PubMed2003

Single dexamethasone injection increases alveolar fluid clearance in adult rats.

OBJECTIVE: Epithelial Na+ channels and Na+/K+-adenosine triphosphatase (ATPase) in alveolar epithelium have a very important role in the absorption of excessive fluid from the alveolar space. We examined whether single dexamethasone injection at therapeutic doses would modulate lung epithelial Na+ channels and Na+/K+-ATPase and increase alveolar fluid clearance in adult rats. DESIGN: Controlled laboratory study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats (n = 138). INTERVENTIONS: Rats were intraperitoneally injected with dexamethasone at a dose ranging from 0.02 to 2.0 mg/kg, and allowed free access to food and water. MEASUREMENTS AND MAIN RESULTS: Alveolar fluid clearance was determined by measuring the increase in albumin concentration in the lung instillate solution. We discovered a significant increase in alveolar fluid clearance at 48 and 72 hrs after dexamethasone treatment. The effect of dexamethasone was dose dependent. In addition, increased alveolar fluid clearance was associated with a faster recover from hypoxemia, which was induced by filling the alveolar space with instillate solution. The dexamethasone-induced increase in alveolar fluid clearance was inhibited by amiloride and ouabain. Quantitative reverse transcriptase-polymerase chain reaction showed that dexamethasone treatment increased lung beta-epithelial Na+ channel mRNA levels. The expression of gamma-epithelial Na+ channel mRNA was also increased slightly. In contrast, alpha-epithelial Na+ channel mRNA levels did not differ from control levels. There was no change in alpha1- or beta1-Na+/K+-ATPase mRNA levels over 72 hrs after dexamethasone treatment. However, we found that lung Na+/K+-ATPase hydrolytic activity, determined by monitoring the ouabain-sensitive ATPase hydrolysis, was increased at 48 and 72 hrs after dexamethasone treatment. CONCLUSIONS: Single dexamethasone injection at therapeutic doses is capable of modulating lung epithelial Na+ channels and Na+/K+-ATPase and increase alveolar fluid clearance, thereby accelerating recovery from pulmonary edema.

Animals↗

PubMed2003

Expression of 11 beta-hydroxysteroid dehydrogenase type 1 in alveolar epithelial cells in rats.

11beta-Hydroxysteroid dehydrogenase type 1 (11beta-HSD1) behaves predominantly as an oxoreductase converting the receptor-inactive glucocorticoids to their active forms in vivo, while the type 2 isoform (11beta-HSD2) possesses only dehydrogenase activity and inactivates cortisol in human or corticosterone in rat. We determined enzyme activity of 11beta-HSD in rat lungs from fetus to adult, and examined whether 11beta-HSD1 exists in alveolar type II cells, the most important site for the synthesis of pulmonary surfactant in mature lungs, by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR). Enzyme activity of 11beta-HSD1 and 2 in lung tissue homogenate were determined as NADP(+)- and NAD(+)-dependent conversion of corticosterone to 11-dehydrocorticosterone, respectively. We found that 11beta-HSD1 activity was increased progressively from 21 days gestation to 7 weeks after birth. 11beta-HSD2 activity was significantly lower than that of 11beta-HSD1 throughout gestation and after birth. Immunoreactivity for 11beta-HSD1 was detected in the cytoplasm of the cells in the alveolar region of adult rats. Some of these expressing 11beta-HSD1 were considered to be alveolar type II cells, because of their cuboid shape and localization at the corner of the alveoli. RT-PCR demonstrated 11beta-HSD1 mRNA in isolated alveolar type II cells. Our results suggest that alveolar type II cells enhance intracellular glucocorticoid availability via 11beta-HSD1. 11beta-HSD1 in alveolar type II cells is thought of as an autocrine amplifier of glucocorticoid action in the lung.

11-beta-Hydroxysteroid Dehydrogenase Type 1↗