Epithelial remodeling probably contributes to parenchymal deterioration in usual interstitial pne... more Epithelial remodeling probably contributes to parenchymal deterioration in usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF), but understanding its mechanisms is still a challenge. The aim of our study was to examine apoptosis and the epithelial changes in the histologic pattern of UIP. After immunohistochemical staining we quantified the content of type I cells, type II cells, surfactant-A protein, bcl-2, and Fas-ligand (Fas-L) in control and alveolar collapse, fibroblastic foci, and honeycomb in UIP areas of 23 open lung biopsies. A significant association was found between epithelial changes and parenchymal deterioration (p < 0.05). Type I epi-thelial cell density was similar between control (1.7 ± 0.7%) and UIP alveolar collapse areas (1.8 ± 0.6%) but decreased progressively in fibroblastic foci zones (0.8 ± 0.4%) and honeycomb changes (0.4 ± 0.3%). Type II cell density increased from control (25.6 ± 8.3%) to areas of alveolar collapse (34.5 ± 11.4%), then decreased toward fibroblastic foci (15.4 ± 6.0%) and honeycomb change areas (23.1 ± 8.6%). The surfactant-A protein increased from control (6.7 ± 3.2%) to areas of alveolar collapse (31.1 ± 9.5%) and decreased toward fibroblastic foci (14.5 ± 4.9%) and honeycomb change areas (21.1 ± 8.9%). Fas-L positive epithelial cell density presented a progressive decline from control (48.5 ± 9.5%), alveolar collapse (37.9 ± 12.4%), fibroblastic foci (27.4 ± 6.8%), and honeycomb change areas (21.9 ± 6.5%). A similar decline in density was found for bcl-2 positive epi-thelial cells from control (20.4 ± 2.7%), alveolar collapse (18.9 ± 5.1%), and fibroblastic foci areas (13.8 ±2.9%), then increased honeycomb change areas (16.3 ± 2.8%). We conclude that loss of the nuclear (bcl-2) and membrane (Fas-L) regulation of normal cell population density and suppression of cell death by apoptosis in UIP may be a determinant of the abnormal epithelial/parenchymal remodeling in UIP.
Recently, several reports suggest differences in the vascularization of the various histopatholog... more Recently, several reports suggest differences in the vascularization of the various histopathologic patterns of parenchymal remodeling seen in usual interstitial pneumonia (UIP). In this study, we sought to validate the importance of vascular remodeling in patients with idiopathic pulmonary fibrosis (IPF) and to examine the relationship between vascular remodeling and parenchymal remodeling or pulmonary function. Open lung biopsies were performed in 57 patients with IPF, and vascular changes in alternating areas of parenchymal remodeling (UIP histologic patterns) were studied. Quantitative analysis of the internal area, internal perimeter, wall thickness, and surrounding cellularity of medium or large pulmonary arteries, as well as their distribution according to air/parenchymal ratios, was performed. Semiquantitative analysis also was used to determine the grade of vascular occlusion. An inverse association was found between vascularization and UIP parenchymal remodeling (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05); that is, the decreased internal luminal area and perimeter as well as the increased wall thickness run in parallel with progression from alveolar collapse toward severe mural-organizing fibrosis with honeycombing. Vascular regression (diminished internal area and perimeter of vessels) was also associated with higher FEV(1), FVC, and RV values (r = 0.48, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), reflecting a tight relationship between vascular remodeling and pulmonary function. A progressive regression of vascularization, reflected by different degrees of luminal occlusion after vascular remodeling, coincided with parenchymal remodeling (alveolar collapse, mural-organizing fibrosis, and honeycombing). This vascular regression may be responsible for the impaired wound healing and progressive fibroproliferation found in patients with IPF. Further studies are needed to determine whether this relationship is causal or consequential.
There were 49 patients studied, coming from The Liver Unit at the &quot;Hospital das Clinicas... more There were 49 patients studied, coming from The Liver Unit at the &quot;Hospital das Clinicas da Faculdade de Medicina da USP (N=41) and from &quot;Prof. Dr. Angelita Habr-Gama and Joaquim Gama-Rodrigues Surgery Institute&quot;, SP (N=8); all of which had hepatic metastasis of colorectal adenocarcinoma, with no evidence of concurrent metastasis in any other organs and were submitted to surgical treatment, during the period of 1992 to 2002, with the aim of analyzing the immunoexpression of the p53, ki-67, p16 and molecular markers in order to relate the disease-free period with the prognosis. The patient&#39;s clinical data were analyzed retrospectively for verification of information such as age, gender, size of the hepatic metastasis and/or the largest lesion, number of satellite nodules resected and compromised, margin of resection free from neoplasia. The immunoexpression of the p53 was associated with the shortest period of life free from disease (p = 0.04). The proliferation marker ki-67 was not associated with the reduction of the disease-free interval and survival; the immunoexpression of the proliferation marker p16 was not associated with the reduction of disease-free period and survival, however, it was associated with hepatic metastasis synchronism. In patients who received postoperative systemic chemotherapy with 5-FU and leucovorin, the immunoexpression on the hepatic metastasis was not associated with a longer disease-free interval. Molcular markers may be useful to evaluate hepatic metastasis of colorectal Adenocarcinoma.
The Annals of otology, rhinology, and laryngology, 2010
Perifascial areolar tissue (PAT) consists of loose areolar tissue with viscoelastic properties th... more Perifascial areolar tissue (PAT) consists of loose areolar tissue with viscoelastic properties that are similar to those found in tissues in the superficial layer of the vocal fold. The aim of this study was to quantify the inflammatory process and the collagen content of the graft, as well as that of the host tissue, after placement of a strip of PAT into the rabbit vocal fold. Surgeries were performed on 30 rabbits. The grafts were implanted in pockets that were surgically created in the right vocal fold. The left vocal fold (control group) was subjected only to surgical manipulation. The animals were divided into 3 groups for evaluations at 15 days, 3 months, and 6 months, and their larynx tissues were subsequently reviewed by histology. The grafts were characterized by disorganized and thick collagen bundles and were identified in all study groups. The collagen density stayed constant over time. There was an acute inflammatory response induced by the graft at 15 days that did no...
Interactive cardiovascular and thoracic surgery, 2009
Ramicotomy is a surgical procedure, with less adverse effects than conventional sympathectomy, ho... more Ramicotomy is a surgical procedure, with less adverse effects than conventional sympathectomy, however, it was abandoned due to the high recurrence rate. Twenty-eight pigs underwent bilateral videothoracoscopic ramicotomy and were divided into five groups. The animals were sacrificed at 15th, 45th, 90th, 135th and 180th postoperative days (POD). The segments were removed and evaluated for macroscopic regeneration and histological analysis. The data were compared to the control group of 10 intact segments of the sympathetic. There was no macroscopic regeneration on the 15th POD, and present on 41.6% on the 180th POD (P<0.05). The Schwann cells presented a similar evolution in both rami beginning at the 45th POD, with a smaller count in the gray rami. The collagen and reticular fibers presented a negative correlation (r=-0.414; P<0.01). The deposition of the collagen fibers was greater in the gray rami with a peak deposition on the 135th POD and a diminishing rate in the 180th P...
Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in ... more Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Here, we investigated whether EMT was present in patients with IPF (n = 19), non-IPF (n = 17), and SRIF (n = 16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (αSMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and αSMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1(+)-cells and low rate of αSMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1(+)cells and αSMA(+)cells, which were present in SRIF and non-IPF more often than IPF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense αSMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.
/ Thematic Poster Session / Tuesday, May 17/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), C69 L... more / Thematic Poster Session / Tuesday, May 17/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), C69 LUNG CANCER BIOMARKERS ... Hyaluronic Acid: A Potential Biochemical Marker For Diagnosis And Prognosis Of Patients With Lung Cancer ... , J. Maciel Martins , ER ...
Epithelial remodeling probably contributes to parenchymal deterioration in usual interstitial pne... more Epithelial remodeling probably contributes to parenchymal deterioration in usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF), but understanding its mechanisms is still a challenge. The aim of our study was to examine apoptosis and the epithelial changes in the histologic pattern of UIP. After immunohistochemical staining we quantified the content of type I cells, type II cells, surfactant-A protein, bcl-2, and Fas-ligand (Fas-L) in control and alveolar collapse, fibroblastic foci, and honeycomb in UIP areas of 23 open lung biopsies. A significant association was found between epithelial changes and parenchymal deterioration (p < 0.05). Type I epi-thelial cell density was similar between control (1.7 ± 0.7%) and UIP alveolar collapse areas (1.8 ± 0.6%) but decreased progressively in fibroblastic foci zones (0.8 ± 0.4%) and honeycomb changes (0.4 ± 0.3%). Type II cell density increased from control (25.6 ± 8.3%) to areas of alveolar collapse (34.5 ± 11.4%), then decreased toward fibroblastic foci (15.4 ± 6.0%) and honeycomb change areas (23.1 ± 8.6%). The surfactant-A protein increased from control (6.7 ± 3.2%) to areas of alveolar collapse (31.1 ± 9.5%) and decreased toward fibroblastic foci (14.5 ± 4.9%) and honeycomb change areas (21.1 ± 8.9%). Fas-L positive epithelial cell density presented a progressive decline from control (48.5 ± 9.5%), alveolar collapse (37.9 ± 12.4%), fibroblastic foci (27.4 ± 6.8%), and honeycomb change areas (21.9 ± 6.5%). A similar decline in density was found for bcl-2 positive epi-thelial cells from control (20.4 ± 2.7%), alveolar collapse (18.9 ± 5.1%), and fibroblastic foci areas (13.8 ±2.9%), then increased honeycomb change areas (16.3 ± 2.8%). We conclude that loss of the nuclear (bcl-2) and membrane (Fas-L) regulation of normal cell population density and suppression of cell death by apoptosis in UIP may be a determinant of the abnormal epithelial/parenchymal remodeling in UIP.
Recently, several reports suggest differences in the vascularization of the various histopatholog... more Recently, several reports suggest differences in the vascularization of the various histopathologic patterns of parenchymal remodeling seen in usual interstitial pneumonia (UIP). In this study, we sought to validate the importance of vascular remodeling in patients with idiopathic pulmonary fibrosis (IPF) and to examine the relationship between vascular remodeling and parenchymal remodeling or pulmonary function. Open lung biopsies were performed in 57 patients with IPF, and vascular changes in alternating areas of parenchymal remodeling (UIP histologic patterns) were studied. Quantitative analysis of the internal area, internal perimeter, wall thickness, and surrounding cellularity of medium or large pulmonary arteries, as well as their distribution according to air/parenchymal ratios, was performed. Semiquantitative analysis also was used to determine the grade of vascular occlusion. An inverse association was found between vascularization and UIP parenchymal remodeling (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05); that is, the decreased internal luminal area and perimeter as well as the increased wall thickness run in parallel with progression from alveolar collapse toward severe mural-organizing fibrosis with honeycombing. Vascular regression (diminished internal area and perimeter of vessels) was also associated with higher FEV(1), FVC, and RV values (r = 0.48, p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05), reflecting a tight relationship between vascular remodeling and pulmonary function. A progressive regression of vascularization, reflected by different degrees of luminal occlusion after vascular remodeling, coincided with parenchymal remodeling (alveolar collapse, mural-organizing fibrosis, and honeycombing). This vascular regression may be responsible for the impaired wound healing and progressive fibroproliferation found in patients with IPF. Further studies are needed to determine whether this relationship is causal or consequential.
There were 49 patients studied, coming from The Liver Unit at the &quot;Hospital das Clinicas... more There were 49 patients studied, coming from The Liver Unit at the &quot;Hospital das Clinicas da Faculdade de Medicina da USP (N=41) and from &quot;Prof. Dr. Angelita Habr-Gama and Joaquim Gama-Rodrigues Surgery Institute&quot;, SP (N=8); all of which had hepatic metastasis of colorectal adenocarcinoma, with no evidence of concurrent metastasis in any other organs and were submitted to surgical treatment, during the period of 1992 to 2002, with the aim of analyzing the immunoexpression of the p53, ki-67, p16 and molecular markers in order to relate the disease-free period with the prognosis. The patient&#39;s clinical data were analyzed retrospectively for verification of information such as age, gender, size of the hepatic metastasis and/or the largest lesion, number of satellite nodules resected and compromised, margin of resection free from neoplasia. The immunoexpression of the p53 was associated with the shortest period of life free from disease (p = 0.04). The proliferation marker ki-67 was not associated with the reduction of the disease-free interval and survival; the immunoexpression of the proliferation marker p16 was not associated with the reduction of disease-free period and survival, however, it was associated with hepatic metastasis synchronism. In patients who received postoperative systemic chemotherapy with 5-FU and leucovorin, the immunoexpression on the hepatic metastasis was not associated with a longer disease-free interval. Molcular markers may be useful to evaluate hepatic metastasis of colorectal Adenocarcinoma.
The Annals of otology, rhinology, and laryngology, 2010
Perifascial areolar tissue (PAT) consists of loose areolar tissue with viscoelastic properties th... more Perifascial areolar tissue (PAT) consists of loose areolar tissue with viscoelastic properties that are similar to those found in tissues in the superficial layer of the vocal fold. The aim of this study was to quantify the inflammatory process and the collagen content of the graft, as well as that of the host tissue, after placement of a strip of PAT into the rabbit vocal fold. Surgeries were performed on 30 rabbits. The grafts were implanted in pockets that were surgically created in the right vocal fold. The left vocal fold (control group) was subjected only to surgical manipulation. The animals were divided into 3 groups for evaluations at 15 days, 3 months, and 6 months, and their larynx tissues were subsequently reviewed by histology. The grafts were characterized by disorganized and thick collagen bundles and were identified in all study groups. The collagen density stayed constant over time. There was an acute inflammatory response induced by the graft at 15 days that did no...
Interactive cardiovascular and thoracic surgery, 2009
Ramicotomy is a surgical procedure, with less adverse effects than conventional sympathectomy, ho... more Ramicotomy is a surgical procedure, with less adverse effects than conventional sympathectomy, however, it was abandoned due to the high recurrence rate. Twenty-eight pigs underwent bilateral videothoracoscopic ramicotomy and were divided into five groups. The animals were sacrificed at 15th, 45th, 90th, 135th and 180th postoperative days (POD). The segments were removed and evaluated for macroscopic regeneration and histological analysis. The data were compared to the control group of 10 intact segments of the sympathetic. There was no macroscopic regeneration on the 15th POD, and present on 41.6% on the 180th POD (P<0.05). The Schwann cells presented a similar evolution in both rami beginning at the 45th POD, with a smaller count in the gray rami. The collagen and reticular fibers presented a negative correlation (r=-0.414; P<0.01). The deposition of the collagen fibers was greater in the gray rami with a peak deposition on the 135th POD and a diminishing rate in the 180th P...
Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in ... more Fibroblastic foci (FF) are a major histological feature of usual interstitial pneumonia (UIP) in idiopathic pulmonary fibrosis (IPF) and collagen vascular diseases (non-IPF). In addition, FF are occasionally associated with smoking-related interstitial fibrosis (SRIF). Recent studies have suggested a role for epithelial to mesenchymal transition (EMT) in pulmonary fibrogenesis. Here, we investigated whether EMT was present in patients with IPF (n = 19), non-IPF (n = 17), and SRIF (n = 16) using morphometric immunohistochemistry, electron microscopy, and confocal microscopy. All patients had received lung biopsies or lobectomies for lung cancer. IPF and non-IPF patients displayed restrictive lung function patterns, whereas those with SRIF presented mixed patterns. Cells within FF presented high number of alpha-smooth muscle actin (αSMA)-staining cells; however, the foci of IPF patients showed comparatively lower number. Moreover, colocalization of thyroid transcription factor-1 (TTF1) and αSMA within FF showed low number of staining cells for IPF and SRIF in comparison to non-IPF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01). Nevertheless, all groups displayed colocalization of high rate of TTF1(+)-cells and low rate of αSMA(+)-cells within hyperplastic epithelioid cells in FF. Also, we observed areas with low proportion of TTF1(+)cells and αSMA(+)cells, which were present in SRIF and non-IPF more often than IPF (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Electron microscopy revealed small breaks in the alveolar basal lamina, which allowed epithelioid cells to directly contact the collagenous matrix and fibroblasts. Three-dimensional reconstruction revealed intense αSMA staining within some epithelioid cells, suggesting that they had gained a mesenchymal phenotype. These findings constitute the first report of EMT in SRIF and suggest that EMT occurs more prominently in SRIF and non-IPF than IPF.
/ Thematic Poster Session / Tuesday, May 17/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), C69 L... more / Thematic Poster Session / Tuesday, May 17/8:15 AM-4:30 PM / Area L, Hall B (Upper Level), C69 LUNG CANCER BIOMARKERS ... Hyaluronic Acid: A Potential Biochemical Marker For Diagnosis And Prognosis Of Patients With Lung Cancer ... , J. Maciel Martins , ER ...
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