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Y C Gary Lee

Publications and source records attributed to Y C Gary Lee.

At least 19 recordsLinked to original sources
PubMed2026

BAP1 Loss in Pleural Mesothelioma Is Associated With Reduced Soluble CCL2 in Patient Effusion, Abrogated CCL2-Mediated Monocyte Recruitment In Vitro.

OBJECTIVES: Pleural mesothelioma is an incurable cancer of the cell layer lining the chest wall and lung. Patients frequently present with pleural effusion, which is often drained for symptom relief and enables minimally invasive sampling of the tumour environment, including immune cells and related soluble factors. Most of the mesothelioma tumours exhibit loss of BRCA1-associated protein 1 (BAP1), a multifunctional tumour suppressor protein. Here, we aim to elucidate the effect of BAP1 loss on the mesothelioma microenvironment through profiling soluble factors within pleural effusion. METHODS: A custom panel of 22 soluble factors was measured by Luminex assay and enzyme-linked immunosorbent assay in an initial cohort of 40 patients with known BAP1 status. Validation was performed by enzyme-linked immunosorbent assay in an independent cohort of 100 cases. Secretion of soluble factors and chemoattraction of monocytes were characterised using a CRISPR-mediated BAP1 deletion model in a mesothelioma and a lung cancer cell line. Immune cell infiltration, estimated by CIBERSORT, was further explored in the Cancer Genome Atlas -MESO cohort. RESULTS: Soluble C-C motif chemokine ligand 2 (CCL2) was approximately 55% to 60% lower in pleural effusion from BAP1-loss cases in both independent cohorts. Deletion of BAP1 reduced CCL2 secretion in vitro and abolished CCL2-mediated chemoattraction of monocytes in both mesothelioma and lung cancer cell lines. In the Cancer Genome Atlas -MESO cohort, BAP1-mutant tumours exhibited a reduction in estimated macrophage content. CONCLUSION: Loss of BAP1 impairs CCL2 secretion into pleural effusions, potentially influencing monocyte recruitment into the tumour microenvironment.

BAP1↗
PubMed2006

Asbestos-induced and smoking-related disease: apportioning pulmonary function deficit by using thin-section CT.

PURPOSE: To retrospectively correlate the extent of individual diseases seen at thin-section computed tomography (CT) with pulmonary function in an initial group of patients with asbestos-related parenchymal disease (asbestosis) and to test these findings in a subsequent group of patients whose CT scans were retrospectively identified. MATERIALS AND METHODS: This retrospective study had Institutional Review Board approval; informed consent was not required. The study included 133 individuals who had been exposed to asbestos. In the initial study group (81 patients; 79 men, two women; median age, 67 years), two observers used a CT scoring system to quantify the extent of pulmonary fibrosis, diffuse pleural thickening, small-airways disease, and emphysema. Multivariate equations were formulated by using independent CT variables to predict changes in total lung capacity (TLC) and carbon monoxide diffusing capacity (Dlco). The validity of these equations was then tested in a subsequent group of patients (52 patients; all men; median age, 60 years). RESULTS: At thin-section CT, the extent of asbestos-induced pleuropulmonary disease and emphysema correlated significantly with physiologic impairment (P<.001). Combined CT variables predicted 58% and 57% of the variability in TLC and Dlco, respectively, despite considerable variation in the proportion of coexisting pathologic conditions. When predictive equations with CT variables derived from the initial study group were applied to the subsequent study group, predicted TLC (rho=0.75, P<.001) and Dlco (rho=0.64, P<.001) correlated strongly with measured values. CONCLUSION: The proposed CT system provides a semiquantitative method for assessing the relative contribution of asbestos-induced pleuropulmonary disease and smoking-related emphysema to functional impairment.

Aged↗
PubMed2006

Management of malignant pleural mesothelioma.

Malignant mesothelioma is increasing in incidence globally and has no known cure. Its unique clinical feature of local infiltration along tissue planes makes it a difficult neoplasm to manage. There have been few randomized controlled trials regarding treatment options, although these have increased in recent years, and results are eagerly awaited. This article summarizes important advances in the management of mesothelioma, especially diagnostic and therapeutic aspects.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2006

Growth factors in pleural fibrosis.

PURPOSE OF REVIEW: Pleural fibrosis is a double-edged sword in clinical settings. Successful induction of pleural fibrosis is the basis of therapeutic pleurodesis. On the other hand, pleural septations and fibrosis are undesirable outcomes in pleural infection and fibrothoraces. The significance of growth factors in the pathogenesis of pleural fibrosis has become increasingly apparent. RECENT FINDINGS: Recent findings have indicated that transforming growth factor beta is a key mediator of pleural fibrosis and demonstrated the therapeutic potential of both transforming growth factor beta itself and transforming growth factor beta inhibitors. Basic fibroblast growth factor has been highlighted as a key factor in successful pleurodesis, and in the formation of pleural effusions. Vascular endothelial growth factor inhibition has been shown to decrease pleural fibrosis in vivo. By contrast, hepatocyte growth factor stimulates non-fibrotic healing, while inhibition increases fibrosis. SUMMARY: The actions of the growth factors, and their inhibitors, are potentially and/or currently applicable in a clinical setting. Understanding the biology of these growth factors may allow therapeutic manipulation of these cytokines to create pleurodesis or to inhibit pleural (and peritoneal) adhesion/fibrosis.

Fibroblast Growth Factor 2↗
PubMed2005

Lymphocytes in pleural disease.

PURPOSE OF REVIEW: Lymphocytic pleural effusions are characterised by divergent cellular responses depending on the etiology of disease. The pathogenic role of lymphocytes in pleural disease, however, remains unclear. This review provides a basic description of the functions of the different lymphocyte subsets within the pleural space and then summarises recent studies of lymphocyte biology in pleural disease. RECENT FINDINGS: The mechanisms of lymphocyte trafficking into the pleural space have been clarified. Specific adhesion molecules (such as intercellular adhesion molecule-1 and vascular cell adhesion molecule-1) and chemokines (CXCL13, interleukin-8, and monocyte chemotactic protein-1) have been identified as important factors involved in the accumulation of lymphocytes during inflammatory pleuritis. Both cellular and soluble factors may contribute to impaired T-cell immunity in malignant pleural effusions. Studies of natural killer cell and gammadelta T-cell biology indicate that these lymphocyte subsets may also play a role in the pathogenesis of pleural disease. The dominant Th1 response characterised by tuberculous pleuritis may allow for rapid diagnosis of disease. Furthermore, strategies for improving cytotoxic T-cell and natural killer cell function show promise for treatment of malignant pleural disease. SUMMARY: Recent work has provided insight into the pathogenesis of disease in lymphocytic pleural effusions. Further study of specific cellular responses may offer significant opportunities in the diagnosis and management of these disorders.

Cell Movement↗
PubMed2004

Activation of proteinase-activated receptor-2 in mesothelial cells induces pleural inflammation.

Pleural inflammation underlies many pleural diseases, but its pathogenesis remains unclear. Proteinase-activated receptor-2 (PAR(2)) is a novel seven-transmembrane receptor with immunoregulatory roles. We hypothesized that PAR(2) is present on mesothelial cells and can induce pleural inflammation. PAR(2) was detected by immunohistochemistry in all (19 parietal and 11 visceral) human pleural biopsies examined. In cultured murine mesothelial cells, a specific PAR(2)-activating peptide (SLIGRL-NH(2)) at 10, 100, and 1,000 muM stimulated a 3-, 42-, and 1,330-fold increase of macrophage inflammatory protein (MIP)-2 release relative to medium control, respectively (P < 0.05 all) and a 2-, 32-, and 75-fold rise over the control peptide (LSIGRL-NH(2), P < 0.05 all). A similar pattern was seen for TNF-alpha release. Known physiological activators of PAR(2), tryptase, trypsin, and coagulation factor Xa, also stimulated dose-dependent MIP-2 release from mesothelial cells in vitro. Dexamethasone inhibited the PAR(2)-mediated MIP-2 release in a dose-dependent manner. In vivo, pleural fluid MIP-2 levels in C57BL/6 mice injected intrapleurally with SLIGRL-NH(2) (10 mg/kg) were significantly higher than in mice injected with LSIGRL-NH(2) or PBS (2,710 +/- 165 vs. 880 +/- 357 vs. 88 +/- 46 pg/ml, respectively; P < 0.001). Pleural fluid neutrophil counts were higher in SLIGRL-NH(2) group than in the LSIGRL-NH(2) and PBS groups (by 40- and 26-fold, respectively; P < 0.05). This study establishes that activation of mesothelial cell PAR(2) potently induces the release of inflammatory cytokines in vitro and neutrophil recruitment into the pleural cavity in vivo.

Animals↗
PubMed2004

CD56bright NK cells are enriched at inflammatory sites and can engage with monocytes in a reciprocal program of activation.

Human NK cells may be divided into a CD56(dim) subset and a CD56(bright) subset. In peripheral blood, CD56(dim) NK cells dominate, whereas in lymph nodes, CD56(bright) NK cells are more common. In this study we show that CD56(bright) NK cells accumulate within inflammatory lesions in a wide variety of clinical diseases affecting several different anatomical sites. We demonstrate that when activated by the monokines IL-12, IL-15, and IL-18, these NK cells promote TNF-alpha production by CD14(+) monocytes in a manner that is dependent on cell:cell contact. Conversely, CD14(+) monocytes synergize with monokines to promote IFN-gamma production by these NK cells. Again, this interaction is dependent on cell:cell contact. The experiments show that CD56(bright) NK cells accumulate in inflammatory lesions and, in the appropriate cytokine environment, can engage with CD14(+) monocytes in a reciprocal activatory fashion, thereby amplifying the inflammatory response. Such a positive feedback loop is likely to be important in the pathogenesis of chronic inflammatory conditions such as rheumatoid arthritis.

Arthritis, Rheumatoid↗
PubMed2004

Randomized trials describing lung inflammation after pleurodesis with talc of varying particle size.

We report two trials describing whether talc pleurodesis with a mean particle size of less than 15 microm ("mixed" talc) produces more lung and systemic inflammation than tetracycline or "graded" talc (most particles < 10 microm were removed). First, 20 patients with malignant effusions received tetracycline or mixed talc. Changes in lung and systemic inflammation from lung clearance scans, oxygen saturations, and C-reactive protein from baseline to 48 hours after pleurodesis were recorded. Lung inflammation (change in isotope clearance, talc -9.26, SD 14.3 vs. tetracycline 4.10, SD 13.8 minutes; difference = -13.4; 95% confidence interval [CI], -26.6 to -0.2; p = 0.05) and systemic inflammation (change in C-reactive protein, talc 198 SD 79.2 vs. tetracycline 74 SD 79.4 microg/L; difference = 124; 95% CI, 50 to 199; p = 0.004) were greater after talc. Second, 48 patients received mixed or graded talc, and gas exchange was assessed from changes in the alveolar-arterial oxygen gradient. Mixed talc worsened gas exchange (oxygen gradient change, mixed 2.17 SD 1.74 kPa, 16.3 13.1 mm Hg vs. graded 0.72 SD 2.46 kPa 5.4 18.5 mm Hg, difference = 1.45; 95% CI, 0.2 to 2.7; p = 0.03) and induced more systemic inflammation than graded talc. We conclude that the routine use of graded talc for pleurodesis would reduce the morbidity of this procedure.

Blood Gas Analysis↗
PubMed2004

Pleurodesis for malignant pleural effusions: current controversies and variations in practices.

PURPOSE OF REVIEW: Malignant pleural effusions are common, and pleurodesis remains the best method to control re-accumulation of the pleural fluid. There are few randomized controlled trials studying the optimal management of malignant pleural effusions. A recent international survey of pleurodesis practice has highlighted variations in how pleurodesis is performed worldwide. Future research should target these areas of variation to determine the best practice protocols. RECENT FINDINGS: The selection of pleurodesing agents remains controversial. Talc is more effective, but is associated with more adverse effects. Talc pleurodesis is followed by systemic and pulmonary inflammation. This is probably related to systemic embolization of talc following its intrapleural administration, though there are other potential causes that may also play a role. SUMMARY: The practice of pleurodesis varies considerably among individual pulmonologists and among different countries, in most technical aspects. This review serves to highlight some of these variations in practice, as well as reviewing the current literature on pleurodesis practice.

Drainage↗
PubMed2004

Management of malignant pleural effusions.

Malignant pleural effusion is a common clinical problem. Evacuation of the pleural fluid and prevention of its reaccumulation are the main aims of management. Pleurodesis should be attempted early, although considerable practice variations exist in the way it is performed. There is a lack of consensus among respiratory physicians worldwide on the optimal method and agent for pleurodesis. Talc remains the most commonly used pleurodesing compound in most countries. While talc produces a higher success rate than other compounds, it generates more side-effects. The association between talc and ARDS continues to be debated. Ambulatory small-bore pleural catheter drainage followed by intrapleural instillation of a pleurodesing agent is increasingly accepted as an alternative to conventional in-patient pleurodesis. Development of novel methods to control pleural fluid formation should be made a high priority in future pleural research.

Humans↗
PubMed2003

Asbestosis and idiopathic pulmonary fibrosis: comparison of thin-section CT features.

PURPOSE: To identify differences, if any, in thin-section computed tomographic (CT) features between asbestosis and idiopathic pulmonary fibrosis (IPF) and to test the findings in a subset of histopathologically proved cases of usual interstitial pneumonia (UIP) and nonspecific interstitial pneumonia (NSIP). MATERIALS AND METHODS: Consecutive patients with a diagnosis of IPF (n = 212) or asbestosis (n = 74) were included. The relationships derived from the initial comparison were tested in a separate group of biopsy-proved UIP (n = 30) and NSIP (n = 23) cases. Two observers independently scored thin-section CT images for extent, distribution, and coarseness of fibrosis; proportion of ground-glass opacification; severity of traction bronchiectasis; and extent of emphysema. RESULTS: After controlling for extent of fibrosis, patients with asbestosis had coarser fibrosis than those with IPF (odds ratio, 1.52; 95% CI: 1.25, 1.84; P <.001). Compared with the biopsy-proved cases, the asbestosis cases involved coarser fibrosis (after controlling for disease extent) than the NSIP cases (odds ratio, 2.48; 95% CI: 1.49, 4.11; P <.001) but fibrosis similar to that in the UIP cases. A basal and subpleural distribution of disease was usual in all subgroups but significantly more prevalent (P, <.01 to.001) with asbestosis than with UIP or NSIP. CONCLUSION: The thin-section CT pattern of asbestosis closely resembles that of biopsy-proved UIP and differs markedly from that of biopsy-proved NSIP.

Asbestosis↗
PubMed2003

Benign asbestos pleural diseases.

The global incidence of asbestos-related lung diseases is expected to continue to rise. Although much attention is devoted to malignant diseases induced by asbestos, benign asbestos pleural diseases (pleural plaques, benign asbestos-related pleural effusion, diffuse pleural thickening, and rounded atelectasis) are common in clinical practice and often produce diagnostic difficulties. The authors describe the clinical features of benign asbestos-related pleural disease, before focusing on recent advances in radiology and on controversies surrounding the pathogenesis of asbestos-induced pleural injury. Advances in computed tomography have assisted the understanding and diagnosis of these diseases, and increasing evidence suggests radiologic appearances on computed tomography can predict impairment in pulmonary function tests. The pathogenesis of asbestos-induced pleural diseases has also been subject to extensive investigation. Asbestos fibers can provoke pleural inflammation from direct toxicity to mesothelial cells. Inhaled asbestos fibers can also elicit pleural injury indirectly via the release of growth factors and inflammatory cytokines from within the lung. Although progress has been made in the understanding of the mechanisms of asbestos pleural injury, many important questions remain unanswered. The role of genetic factors and possible environmental cofactors (eg, simian virus 40) in the pathogenesis of benign asbestos pleural diseases requires further research.

Asbestos↗
PubMed2003

Pleural space as a site of ectopic gene delivery: transfection of pleural mesothelial cells with systemic distribution of gene product.

STUDY OBJECTIVES: Successful ectopic gene therapy requires the transfection of the cells at the ectopic site, with local and systemic delivery of the gene product. This study aimed to evaluate the pleural mesothelial surface as a potential site for ectopic gene therapy. DESIGN: A secreted placental alkaline phosphatase (PALP) plasmid was injected bilaterally into the pleural spaces of seven rabbits via a chest tube, while an irrelevant reporter plasmid was injected into seven control rabbits. Blood was collected at baseline and at 24, 48, and 72 h after the injections. Pleural fluid was collected by lavage at 24, 48, and 72 h after the injections. The PALP level was measured by chemiluminesence. MEASUREMENTS AND RESULTS: Significant expressions of PALP proteins were observed in the serum of the treatment rabbits, with a threefold increase over baseline at 24 h, a ninefold increase at 48 h, and a twofold increase at 72 h. The serum PALP levels in the control rabbits remained at baseline levels at all time points. The pleural fluid PALP levels peaked at 24 h and decreased over the next 72 h. Mimicking the in vivo pattern, pleural mesothelial cells transfected in vitro demonstrated a similar increase in PALP levels. CONCLUSIONS: The results of the present short-term pilot study suggest that pleural mesothelial cells can be successfully transfected with plasmids, with increases in both the local and systemic levels of the gene product. The pleural space should be further evaluated for ectopic gene therapy.

Alkaline Phosphatase↗
PubMed2003

Ultrasound-guided thoracentesis: is it a safer method?

STUDY OBJECTIVES: The objectives of this study are as follows: (1) to determine the incidence of complications from thoracentesis performed under ultrasound guidance by interventional radiologists in a tertiary referral teaching hospital; (2) to evaluate the incidence of vasovagal events without the use of atropine prior to thoracentesis; and (3) to evaluate patient or radiographic factors that may contribute to, or be predictive of, the development of re-expansion pulmonary edema after ultrasound-guided thoracentesis. DESIGN: Prospective descriptive study. SETTING: Saint Thomas Hospital, a tertiary referral teaching hospital in Nashville, TN. PATIENTS: All patients referred to interventional radiology for diagnostic and/or therapeutic ultrasound-guided thoracentesis between August 1997 and September 2000. RESULTS: A total of 941 thoracenteses in 605 patients were performed during the study period. The following complications were recorded: pain (n = 25; 2.7%), pneumothorax (n = 24; 2.5%), shortness of breath (n = 9; 1.0%), cough (n = 8; 0.8%), vasovagal reaction (n = 6; 0.6%), bleeding (n = 2; 0.2%), hematoma (n = 2; 0.2%), and re-expansion pulmonary edema (n = 2; 0.2%). Eight patients with pneumothorax received tube thoracostomies (0.8%). When > 1,100 mL of fluid were removed, the incidence of pneumothorax requiring tube thoracostomy and pain was increased (p < 0.05). Fifty-seven percent of patients with shortness of breath during the procedure were noted to have pneumothorax on postprocedure radiographs, while 16% of patients with pain were noted to have pneumothorax on postprocedure radiographs. Vasovagal reactions occurred in 0.6% despite no administration of prophylactic atropine. Re-expansion pulmonary edema complicated 2 of 373 thoracenteses (0.5%) in which > 1,000 mL of pleural fluid were removed. CONCLUSIONS: The complication rate with thoracentesis performed by interventional radiologists under ultrasound guidance is lower than that reported for non-image-guided thoracentesis. Premedication with atropine is unnecessary given the low incidence of vasovagal reactions. Re-expansion pulmonary edema is uncommon even when > 1,000 mL of pleural fluid are removed, as long as the procedure is stopped when symptoms develop.

Chest Tubes↗