Hisanaga Yagyu

Effects of acute exercise on lung antioxidant enzymes in young and old rats.

The lung could be the target organ to cellular damage, since it is directly exposed to high concentrations of oxygen. Acute exercise and age would be an added challenge to the lung, and therefore, we investigated alterations of major lung antioxidant enzymes (manganese-superoxide dismutase, Mn-SOD; copper-zinc-SOD, Cu-Zn-SOD; glutathione peroxidase, GPX; catalase, CAT) activities and mRNA expressions in young (4 months old) and old (26 months old) male Wistar rats with exercise. Thioredoxin reductase (TrxR) activity was also investigated. Mn-SOD and Cu-Zn-SOD increased with age, but age did not affect GPX, CAT, or TrxR activity. Acute exercise in young animals increased the activities of Mn-SOD, Cu-Zn-SOD, and CAT. In contrast, only Mn-SOD increased significantly in the old animals. The mRNA expressions of Mn-SOD, Cu-Zn-SOD and GPX were not altered with age, while CAT mRNA expression decreased with age. Acute exercise had no significant effect on any of the antioxidant enzyme mRNA expression. Moreover, reactive carbonyl derivative increased with age, but no significant changes were detected after acute exercise in either group. In summary, antioxidant enzymes responsible for the removal of hydrogen peroxide were unable to increase their enzyme activities in the old animals with exercise.

Gender Differences in the Clinical Characteristics Among Japanese Patients With Obstructive Sleep Apnea Syndrome

BACKGROUND Gender differences in the prevalence of various manifestations of obstructive sleep apnea syndrome (OSAS) is not as great as previously believed. The aim of the present study was to clarify the clinical patient characteristics of Japanese women and men with OSAS. METHODS A cross-sectional case-match control study was performed on patients from two sleep disorder centers. Two hundred forty-five women with OSAS were classified into premenopausal (n = 70) and postmenopausal (n = 175) groups. As well, 245 men matched for both age and apnea-hypopnea index (AHI) and another 245 men matched for age and body mass index (BMI) were established. We compared descriptive variables between genders in both the premenopausal and the postmenopausal female patient groups. RESULTS As a whole, female patients had significantly higher BMI than AHI-matched male patients (p < 0.05) and a significantly lower value of AHI than BMI-matched male patients (p < 0.001). Female patients had lower Epworth Sleepiness Scale scores than BMI-matched male patients (p < 0.05). On logistic regression analysis, presence of hypertension was significantly associated with BMI (>or=25 kg/m(2)), AHI (>or= 15 to < 30 events/h; >or= 30 to < 60 events/h; >or= 60 events/h), and presence of both hyperlipidemia and diabetes mellitus. However, gender differences were not associated with the occurrence of hypertension. Female patients had significantly lower optimal levels of continuous positive airway pressure than male patients. CONCLUSIONS Our results suggest that both the OSAS severity and the strength of pharyngeal closure is less in Japanese female patients than in male patients. Moreover, Japanese female patients are thought to have less daytime sleepiness than male patients but a similar rate of hypertension as male patients.

Increased secretion of urokinase-type plasminogen activator by human lung microvascular endothelial cells

Human lung microvascular endothelial cells (HLMECs) secreted 1.5-15 times more urokinase-type plasminogen activator (uPA) antigen than human hepatic microvascular endothelial cells, human umbilical vein endothelial cells (HUVECs), angioma endothelial cells, and lung fibroblasts. All of these cells also secreted a 100-fold greater amount of plasminogen activator inhibitor-1 than of uPA antigen, and uPA activities were not detected in the culture medium. The expression of uPA mRNA in HLMECs was higher (100-fold) compared with HUVECs, angioma endothelial cells, and lung fibroblasts. HLMECs secreted uPA antigen on both the luminal and basal sides of the cells. On the other hand, HLMECs secreted a 10- to 15-fold lower amount of tissue-type plasminogen activator than HUVECs, mostly on the luminal side. After stimulation with interleukin (IL)-1β, HLMECs secreted a six- to ninefold amount of uPA antigen. In contrast, no stimulatory effect was observed in HUVECs even under high IL-1β concentrations. The secretion of uPA and plasminogen activator inhibitor-1 from HLMECs was also enhanced by tumor necrosis factor-α and IL-2. These results suggest that HLMECs may contribute not only to the patency of lung vessels but also to the maintenance of alveolar functions through the production and secretion of uPA, especially in the presence of inflammatory cytokines.Human lung microvascular endothelial cells (HLMECs) secreted 1.5-15 times more urokinase-type plasminogen activator (uPA) antigen than human hepatic microvascular endothelial cells, human umbilical vein endothelial cells (HUVECs), angioma endothelial cells, and lung fibroblasts. All of these cells also secreted a 100-fold greater amount of plasminogen activator inhibitor-1 than of uPA antigen, and uPA activities were not detected in the culture medium. The expression of uPA mRNA in HLMECs was higher (100-fold) compared with HUVECs, angioma endothelial cells, and lung fibroblasts. HLMECs secreted uPA antigen on both the luminal and basal sides of the cells. On the other hand, HLMECs secreted a 10- to 15-fold lower amount of tissue-type plasminogen activator than HUVECs, mostly on the luminal side. After stimulation with interleukin (IL)-1beta, HLMECs secreted a six- to ninefold amount of uPA antigen. In contrast, no stimulatory effect was observed in HUVECs even under high IL-1beta concentrations. The secretion of uPA and plasminogen activator inhibitor-1 from HLMECs was also enhanced by tumor necrosis factor-alpha and IL-2. These results suggest that HLMECs may contribute not only to the patency of lung vessels but also to the maintenance of alveolar functions through the production and secretion of uPA, especially in the presence of inflammatory cytokines.

Tumor debulking by radiofrequency ablation in hypertrophic pulmonary osteoarthropathy associated with pulmonary carcinoma

A 73-year-old male with stage IV lung adenocarcinoma presented with leg swelling and clubbing of the fingers on both hands upon physical examination, and bone scintigrams demonstrated marked accumulation of 99mTc-MDP in the long bones adjacent to the patellae. A diagnosis of hypertrophic pulmonary osteoarthropathy associated with primary lung cancer was made. Radiofrequency ablation (RFA) was utilized for cytoreduction, because the patient refused chemotherapy. One-month follow-up CT scans revealed low density of the ablated area associated with ablation necrosis. Cytoreduction by RFA rapidly alleviated the arthralgia and swelling, but not the clubbing of fingers. Follow-up bone scintigrams demonstrated a reduction in patellar uptake after RFA.

PRODUCTION OF HEPATOCYTE GROWTH FACTOR FROM HUMAN LUNG MICROVASCULAR ENDOTHELIAL CELLS INDUCED BY INTERLEUKIN-1β

To investigate the possible role of hepatocyte growth factor (HGF)in the reconstruction process following inflammatory damage in lung tissue, we compared HGF production of human lung microvascular endothelial cells (HL MECs) and human umbilical vein endothelial cells (HUVECs) after stimulation by interleukin(IL)-1 β. In an HL MEC-conditioned medium, largeamounts of total (single and 2-chain) HGF were detected, and were 26- to 28-fold higher than those in HUVECs or human lung fibroblasts. The production of total HGF increased in a dose-dependent manner (4.7 to 9.2 times) with IL-1 β. In contrast, the amount of HGF in an HUVEC-conditioned medium was unaffected by IL-1 β treatment. The amount of cell-associated HGF also showed a dose-related increase (140% to 160%) in HL MECs, but not in HUVECs with IL-1 β. In addition, HGF and c-met (HGF receptor) mRNAs in HL MECs and HUVECs were examined by the RT-PCR method. HGF and c-met mRNAs were clearly detected in HL MECs before and after treatment with IL-1 β, but not in HUVECs. These results suggest that increases in HGF production from HL MECs may play a role in the reconstruction process following inflammatory damage in lung tissue.To investigate the possible role of hepatocyte growth factor (HGF) in the reconstruction process following inflammatory damage in lung tissue, we compared HGF production of human lung microvascular endothelial cells (HLWECs) and human umbilical vein endothelial cells (HUVECs) after stimulation by interleukin(IL)-1beta. In an HLMEC-conditioned medium, large amounts of total (single and 2-chain) HGF were detected, and were 26- to 28-fold higher than those in HUVECs or human lung fibroblasts. The production of total HGF increased in a dose-dependent manner (4.7 to 9.2 times) with IL-1beta. In contrast, the amount of HGF in an HUVEC-conditioned medium was unaffected by IL-1beta treatment. The amount of cell-associated HGF also showed a dose-related increase (140% to 160%) in HLMECs, but not in HUVECs with IL1beta. In addition, HGF and c-met (HGF receptor) mRNAs in HLMECs and HUVECs were examined by the RT-PCR method. HGF and c-met mRNAs were clearly detected in HLMECs before and after treatment with IL-1beta, but not in HUVECs. These results suggest that increases in HGF production from HLMECs may play a role in the reconstruction process following inflammatory damage in lung tissue.

Subthreshold Hyperoxia Potentiates Tnf-α-Induced Icam-1 Expression on Cultured Pulmonary Microvascular Endothelial Cells

The effects of combined exposure to subthreshold hyperoxia and the inflammatory cytokine tumor necrosis factor alpha (TNF-alpha) on the expression of intercellular adhesion molecule-1 (ICAM-1) were examined in bovine lung microvascular endothelial cells (BLuEC). The expression of total ICAM-1 was not affected by 50% hyperoxia conditions alone, indicating that this level is subthreshold for BLuEC. In the presence of 5 ng/mL TNF-alpha, which has minimal influence on BLuEC alone, the amount of total ICAM-1 expression under 50% hyperoxia was higher than that in normoxic conditions (approximately 30%) throughout the culture period. The amount of soluble ICAM-1 that has been released into the culture medium increased after joint exposure to hyperoxia and TNF-alpha. These results suggest that exposure to subthreshold hyperoxia, which does not by itself cause damage to the endothelial cells or induce ICAM-1 expression, potentiates the effects of low-level TNF-alpha exposure.

Correlation between serum cytokeratin 19 fragment and tissue polypeptide antigen levels in patients with non-small cell lung cancer

We evaluated the correlation between serum cytokeratin 19 fragment (CYFRA 21-1) and tissue polypeptide antigen (TPA) levels in 57 non-small cell lung cancer patients. There was a significant correlation between serum CYFRA 21-1 and TPA levels for each clinical stage and TNM (T, primary tumor; N, regional lymph node involvement; M, occurrence of distant metastasis) subcategory (range of r-value = 0.809-0.998, P < 0.01). High correlations between serum CYFRA 21-1 and TPA levels were found in eight patients both before and after the surgery, in 22 patients before and after chemotherapy and in another 27 patients who could not complete the scheduled chemotherapy (range of r-value = 0.856-0.998, P < 0.0001). However the positive rate of CYFRA 21-1 was higher than that of TPA (61% vs. 53%, P < 0.05). CYFRA 21-1 would yield better diagnostic results for non-small cell lung cancers than TPA, though these tumor markers are both cytokeratin-associated tumor markers.

INFECTION OF HUMAN LUNG FIBROBLASTS WITH EPSTEIN-BARR VIRUS CAUSES INCREASED IL-1ß AND bFGF PRODUCTION

An association between Epstein-Barr virus (EBV) infection and fibroblast proliferation in the interstitial spaces of the lung has been suggested in idiopathic interstitial pneumonia. In this study we show that EBV can infect human lung fibroblasts in vitro. A primary-cultured human lung fibroblast cell line, designated CCD-32Lu, expressed EBV nuclear antigen 1 after coculture with lethally irradiated EBV producing cells. The infection further induced CCD-32Lu cells to produce the fibrogenic cytokines basic fibroblast growth factor (bFGF) and interleukin-1beta. These findings indicate that lung fibroblasts may be a target for EBV infection and suggest that EBV may play a role in increased production of these cytokines and induce fibroblast proliferation in idiopathic interstitial pneumonia.