Search

The potential of the A549 type II epithelial cell line to release granulocyte colony-stimulating factor (G-CSF) as neutrophil chemotactic activity (NCA) was evaluated. It was demonstrated that A549 cells released G-CSF as NCA in response to interleukin-1 beta, tumor necrosis factor-alpha, lipopolysaccharide and bradykinin. The expression of G-CSF mRNA was augmented in response to each stimulus. These suggested that alveolar type II cells may produce G-CSF as NCA and may participate in the regulation of neutrophil extravasation into the lung.

Experiments were performed to investigate the capacity of the human lung fibroblast (HLF) to induce monocyte chemokinetic activity (MCA) through the release of the transforming growth factor-beta, leukotriene B4 (LTB4) and the granulocyte-macrophage colony-stimulating factor. The attenuation of the MCA and its lowest molecular weight peak was attributed to an LTB4-receptor antagonist. These findings emphasize the role of HLFs as modulators of monocyte recruitment in the lungs.

Cyclophosphamide is an alkylating antineoplastic agent used in several conditions. However, little is known about the mechanism of its pulmonary toxicity. In the present study, we determined that human lung fibroblasts release activity for neutrophils and monocytes in response to cyclophosphamide in a dose- and time-dependent manner. Checkerboard analysis revealed that both neutrophil and monocyte activities were chemotactic. The release of chemotactic activity was inhibited by lipoxygenase inhibitors and cycloheximide. Molecular-sieve column chromatography revealed that both neutrophil (NCA) and monocyte (MCA) chemotactic activities had multiple peaks. NCA was inhibited by a leukotriene [B.sub.4] receptor antagonist and anti-interleukin-8 and anti-granulocyte colony-stimulating factor antibodies. MCA was attenuated by a leukotriene [B.sub.4] receptor antagonist and anti-monocyte chemoattractant protein-1 and anti-granulocyte-macrophage colony-stimulating factor antibodies. The concentrations of interleukin-8, granulocyte colony-stimulating factor, monocyte chemoattractant protein-1, and granulocyte-macrophage colony-stimulating factor significantly increased in response to cyclophosphamide. These data suggest that lung fibroblasts may modulate inflammatory cell recruitment into the lung by releasing NCA and MCA in response to cyclophosphamide. interstitial lung disease; interleukin-8; granulocyte colony-stimulating factor; monocyte chemoattractant protein-1; granulocyte-macrophage colony-stimulating factor

Sato, Etsuro, Sekiya Koyama, Akemi Takamizawa, Takeshi Masubuchi, Keishi Kubo, Richard A. Robbins, Sonoko Nagai, and Takateru Izumi. Smoke extract stimulates lung fibroblasts to release neutrophil and monocyte chemotactic activities. Am. J. Physiol. 277 (Lung Cell. Mol. Physiol. 21): L1149-L1157, 1999.--Accumulation of monocytes and neutrophils and fibrous distortion of the airway are characteristics of airway disease secondary to smoking. The presence of inflammatory cells and fibrosis correlate, and, therefore, we postulated that lung fibroblasts might release chemotactic activity for neutrophils and monocytes in response to smoke extract. To test this hypothesis, human fetal lung (HFL1) fibroblasts were cultured, and the supernatant fluid was evaluated for neutrophil (NCA) and monocyte (MCA) chemotactic activities with a blind well chamber technique. HFL1 fibroblasts released chemotactic activity in response to smoke extract in a dose- and time-dependent manner (P [is less than] 0.05). Checkerboard analysis showed that the activity was predominantly chemotactic. Partial characterization of the released chemotactic activity revealed that the activity was partly heat labile, trypsin sensitive, and ethyl acetate extractable. Lipoxygenase inhibitors and cycloheximide inhibited the release of both NCA and MCA. Molecular-sieve chromatography revealed that NCA and MCA were heterogeneous. NCA was inhibited by anti-human interleukin (IL)-8 and anti-granulocyte colony-stimulating factor antibodies and a leukotriene (LT) [B.sub.4]-receptor antagonist. Anti-granulocyte-macrophage colony-stimulating factor (GM-CSF) and anti-monocyte chemoattractant protein (MCP)-1 antibodies and an [LTB.sub.4]-receptor antagonist inhibited MCA. Immunoreactive IL-8, granulocyte colony-stimulating factor, GM-CSF, and MCP-1 significantly increased in culture supernatant fluid in response to smoke extract. Finally, smoke extract augmented the expression of mRNAs of IL-8, GM-CSF, and MCP-1. These data demonstrate that lung fibroblasts release NCA and MCA in response to smoke extract and suggest that lung fibroblasts may modulate the inflammatory cell recruitment into the lung. interleukin-8; granulocyte colony-stimulating factor; monocyte chemoattractant protein-1; granulocyte-macrophage colony-stimulating factor; fibrosis; chemotaxis; smoking

A study has been conducted to investigate the side effects of the use bleomycin on cancer patients. To determine these effects, tests were done on harvested A549 cell supernatant fluid were evaluated for neutrophil and monocyte chemotactic activities. Findings have confirmed that bleomycin stimulates type II epithelial cells to release chemotactic activities and promote cell inflammation in the lungs, which could develop into diffuse interstitial lung fibrosis.

Methotrexate-induced pneumonitis has been reported as an infrequent but potentially serious complication of therapy in a variety of malignant and benign conditions. Because inflammatory cell infiltration is concerned with the development of methotrexate-induced pneumoinitis, and because airway epithelial cells participate in the orchestration of lung inflammation, the authors determined whether methotrexate might stimulate airway epithelial cells (A549 cells) to release neutrophil, monocyte, and eosinophil chemotactic activities (NCA, MCA, and ECA). A549 cells released NCA, MCA, and ECA in a dose- and time-dependent manner in response to methotrexate. Partial characterization revealed the heterogeneity of NCA, MCA, and ECA. The release of chemo-tactic activity was blocked by lipoxygenase inhibitors and cycloheximide. NCA was inhibited by leukotriene (LT) B[SUB4] receptor antagonist, and anti-interleukin (IL)-8 and granulocyte colony-stimulating factor (G-CSF) antibodies. MCA was attenuated by LTB[SUB4] receptor antagonist, and anti-monocyte chemoattractant protein (MCP)-1 and granulocyte-macrophage CSF (GM-CSF) (antibodies. ECA was attenuated by LTB[SUB4] receptor antagonist, and anti-IL-8 and GM-CSF antibodies. The release of IL-8, G-CSF, MCP-1, GM-CSF, and LTB[SUB4] from A549 cells significantly increased in response to methotrexate. The mRNA expression of IL-8 and MCP-1 was augmented by methotrexate stimulation. These data suggest that type II epithelial cells may modulate inflammatory cell recruitment into the lung by releasing NCA, MCA, and ECA in response to methotrexate. [ABSTRACT FROM AUTHOR]

Background: Optimal chemotherapeutic regimen in thymic carcinoma remains uncertain and the efficacy of second line chemotherapy has not been established either., Patients and Methods: We retrospectively evaluated the efficacy of an irinotecan plus cisplatin or carboplatin (IP) regimen as a salvage treatment for patients with unresectable thymic carcinoma that progressed after cisplatin, doxorubicin, vincristine and cyclophosphamide (ADOC) chemotherapy. Seven patients with histologically confirmed thymic carcinoma that was resistant to or who had relapsed after initial chemotherapy with ADOC were treated with IP. The treatment consisted of irinotecan (CPT-11, 60 mg/m2, days 1, 8 and 15) and cisplatin (80 mg/m2, day 1) or carboplatin (AUC 4) intravenously every 4 weeks, for at least 2 cycles., Result: Two patients achieved partial responses. Although another two patients showed a significant reduction of the primary thoracic lesion, the appearance of a new lesion was found in one and a metastatic lesion was unchanged in the other. Neutropenia over grade 3 was observed in all patients but none of the patients developed serious infections. There were no severe non-hematological toxicities, including diarrhea., Conclusion: We conclude that salvage chemotherapy may be useful in certain patients with thymic carcinoma and irinotecan may be a novel and alternative agent for relapsed thymic carcinoma.

Objective: Simplified sleep polysomnography was performed in 207 adult men to examine the relationship between the frequency of sleep-disordered breathing (SDB) and lifestyle-related illness., Methods: Each subject was checked for SDB using a simplified sleep polysomnograph (Auto-Set Portable; Teijin Limited, Tokyo, Japan). Apnea and hypopnea were detected with a nasal cannula type airflow sensor. Hypoxemia was checked with a percutaneous oxygen saturation (SpO2) monitor. We analyzed the relationships between SDB and body mass index (BMI) and hypertension, hyperlipidemia, liver dysfunction, fatty liver, and abnormal glucose metabolism., Results: Fifty-nine subjects (29%) showed SDB with apnea hypopnea index (AHI) over 15 times/h. The frequency of obesity (BMI > or = 25), hypertension, hypercholesterolemia, fasting blood glucose level, and HbA1c were significantly higher in patients with SDB than in normal individuals (AHI < 5 times/h). The frequencies of hypertension, hyperlipidemia, and abnormal glucose metabolism were compared between the obesity-free normal AHI group and the SDB group, and only that of hypertension was significantly different between the two groups., Conclusions: The present study revealed a high frequency of SDB among Japanese individuals. The results also suggest that as SDB becomes severe, it becomes more closely linked to the onset of lifestyle-related illnesses, such as hypertension, hypercholesterolemia and abnormal glucose metabolism.

Diagnoses of infectious tuberculosis (TB) patients were followed by thorough contact investigation on the basis of our hospital's Infectious Disease Manual ever since an infection of an inpatient with extended hospital stay was confirmed by a positive acid-fast sputum smear in October 1998. In September 2000, a nurse was found to have pulmonary TB and another was given a diagnosis of right tuberculous pleuritis the following November. Contact investigations were expedited among all hospital staff, families of the infected nurses, and all suspected inpatients. Five were diagnosed as TB, 8 were given chemoprophylaxis and 8 others required observation. The result verified a TB outbreak within the hospital, and management of TB infection control was re-enforced subsequently. We concluded that immediate contact investigation promoted successful early diagnosis, and reacknowledged the significance of the health supervision of all staff, operations including the environment and equipment control of the institution, and frequent contact and integration with the administration of the public health center. This experience enabled a useful revision of the disease manual for the future.

The role of systemic chemotherapy and optimal regimen in thymic carcinoma remains uncertain. We evaluated the clinical responsiveness of ADOC (cisplatin, doxorubicin, vincristine, and cyclophosphamide) chemotherapy for advanced thymic carcinoma that have distant metastatic or unresectable lesions. From 1996 to 2000, we treated eight cases of thymic carcinoma. According to the classification by Masaoka et al., the clinical stage in one case was IVa, whereas the others were IVb. Histologic subtypes were as follows: four cases were squamous cell carcinoma, two cases were undifferentiated, and two were small-cell carcinoma. All patients received 50 mg/m2 of cisplatin and 40 mg/m2 of doxorubicin intravenously on day 1, 0.6 mg/m2 of vincristine intravenously on day 3, and 700 mg/m2 of cyclophosphamide intravenously on day 4, ADOC regimen, respectively, at 3- to 4-week intervals. Six patients obtained a partial response after ADOC chemotherapy and the overall clinical response rate was 75%. There were no life-threatening side effects noted. Cisplatin plus VP-16 chemotherapy (PVP) was performed in three cases before the ADOC regimen, but PVP chemotherapy did not show beneficial effects in two patients. Median survival time was 19 months. ADOC chemotherapy appears to have significant activity against thymic carcinoma.