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Biomedical subjects

Kirk B Lane

Publications and source records attributed to Kirk B Lane.

23 records · Page 2Linked to original sources

Transforming growth factor beta induces vascular endothelial growth factor elaboration from pleural mesothelial cells in vivo and in vitro.

Vascular endothelial growth factor (VEGF) increases vascular permeability and is important in pleural effusion formation. In studies using transforming growth factor beta (TGF-beta) to produce pleurodesis, we observed that although TGF-beta was more effective than talc or doxycycline, it induced transient production of large pleural effusions. We hypothesized that TGF-beta stimulates VEGF production in pleural tissues in vivo, and by mesothelial cells in vitro. New Zealand White rabbits (n = 33) were given TGF-beta(2) (1.7 or 5.0 microg), talc (400 mg/kg), doxycycline (10 mg/kg), or buffer intrapleurally. Pleural fluid was collected at 24 h. Intrapleural injection of TGF-beta(2) induced a dose-dependent increase in VEGF production. The pleural fluid VEGF level was 2-fold higher in rabbits given 5.0 microg of TGF-beta(2) than in those given 1.7 microg of TGF-beta(2) and 3-fold higher than in those given buffer. VEGF levels were higher after the injection of TGF-beta(2) than after administration of talc or doxycycline. The pleural fluid VEGF correlated significantly with the volume of pleural effusions (r = 0.79, p < 0.00001). In vitro, TGF-beta(2) stimulated a dose-dependent increase in VEGF production from murine pleural mesothelial cells. At 4 and 24 h, TGF-beta(2), but not talc or doxycycline, induced a significant increase in VEGF, when compared with controls. The mesothelial cell VEGF production was significantly reduced by anti-TGF-beta antibody in the TGF-beta(2), talc, and control (buffer and medium) groups. In conclusion, mesothelial cells are an important source of VEGF. TGF-beta increases the VEGF production by mesothelial cells in vivo and in vitro.

Analysis of Variance↗

Comparing transforming growth factor-beta2, talc and bleomycin as pleurodesing agents in sheep.

BACKGROUND: Transforming growth factor (TGF)-beta2 can produce effective pleurodesis in animals, but its efficacy has not been compared with commonly used pleurodesing agents in sheep, which have a thick pleura resembling that of humans. The acute physiological effects and the level of systemic TGF-beta absorption after its intrapleural administration have not been studied. The aims of the present study were to compare: (i) the effectiveness of TGF-beta2, talc and bleomycin in producing pleurodesis in sheep; (ii) the acute side-effects and systemic TGF-beta levels following the intrapleural administration of these agents; and (iii) histological changes after intrapleural injections of these agents. METHODOLOGY: Twelve sheep were divided into three groups and were given a single intrapleural dose of TGF-beta2 (0.25 microg/kg), talc slurry (5 g) or bleomycin (60 IU) via a chest tube. Saline or buffer was injected into the contralateral side, which served as the control. Arterial blood gases and respiratory and heart rates were monitored for the first 24 h. Plasma levels of TGF-beta1 and TGF-beta2 were measured. Pleurodesis was graded macroscopically from 1 (none) to 8 (symphysis > 50% of hemithorax) at day 14. RESULTS: At day 14, the pleurodesis score of the TGF-beta2 group (7.7+/-0.6) was similar to that of the talc (7.0+/-1.7) group and significantly higher than that of the bleomycin group (3.3+/-2.3; P < 0.05). No significant differences were seen in arterial blood gas analysis, vital signs and plasma TGF-beta1 and TGF-beta2 concentrations among the three groups. CONCLUSIONS: Transforming growth factor-beta2 was as effective as talc and more so than bleomycin in inducing pleurodesis in sheep. Intrapleural administration of TGF-beta2 appeared safe. No acute changes in gaseous exchange or macroscopic abnormalities were seen following intrapleural TGF-beta2. Importantly, there was no evidence of an increase in systemic TGF-beta levels following its intrapleural administration.

Analysis of Variance↗

Pleural fluid levels of interleukin-5 and eosinophils are closely correlated.

BACKGROUND: The mechanisms responsible for the accumulation of eosinophils in pleural fluid are not fully understood. The purpose of this study was to evaluate the relationship between eosinophil accumulation and the levels of interleukin (IL)-5, IL-3, and granulocyte/macrophage colony-simulating factor (GM-CSF) in pleural effusions. METHODS: We evaluated 30 patients with eosinophilic pleural effusions (eosinophil count > 10% nucleated cells in pleural fluid) and 10 patients with noneosinophilic pleural effusions. The patients with eosinophilic pleural effusions included 22 patients with post-coronary artery bypass graft surgery pleural effusions and 8 patients with eosinophilic pleural effusions caused by other causes. IL-5, IL-3, and GM-CSF in all pleural fluids were measured using enzyme-linked immunosorbent assay kits. RESULTS: The mean level of IL-5 in eosinophilic pleural effusions (283.1 +/- 341.6 pg/mL) was significantly (p < 0.025) higher than that in the noneosinophilic effusions (28.2 +/- 19.0 pg/mL). The absolute eosinophil count and percentage correlated significantly with the level of IL-5 in all patients (r = 0.55, p < 0.001, and r = 0.54, p < 0.001, respectively). There was no significant correlation between IL-5 levels and RBC counts in all patients (r = 0.24, p > 0.05). GM-CSF and IL-3 levels were below the detectable range in all pleural fluids. CONCLUSION: There is a significant relationship between the levels of IL-5 in pleural fluid and the total number and percentage of eosinophils in the pleural fluid. IL-5 seems to be related to the eosinophil accumulation associated with blood or air in the pleural space and other eosinophilic pleural effusions.

Enzyme-Linked Immunosorbent Assay↗