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Biomedical subjects

V L Roggli

Publications and source records attributed to V L Roggli.

At least 19 recordsLinked to original sources
PubMed1999

Allergic lung responses are increased in prostaglandin H synthase-deficient mice.

To investigate the function of prostaglandin H synthase-1 and synthase-2 (PGHS-1 and PGHS-2) in the normal lung and in allergic lung responses, we examined allergen-induced pulmonary inflammation and airway hyperresponsiveness in wild-type mice and in PGHS-1(-/-) and PGHS-2(-/-) mice. Among nonimmunized saline-exposed groups, we found no significant differences in lung function or histopathology, although PGE(2) was dramatically reduced in bronchoalveolar lavage (BAL) fluid from PGHS-1(-/-) mice, relative to wild-type or PGHS-2(-/-) mice. After ovalbumin sensitization and challenge, lung inflammatory indices (BAL cells, proteins, IgE, lung histopathology) were significantly greater in PGHS-1(-/-) mice compared with PGHS-2(-/-) mice, and both were far greater than in wild-type mice, as illustrated by the ratio of eosinophils in BAL fluid (8:5:1, respectively). Both allergic PGHS-1(-/-) and PGHS-2(-/-) mice exhibited decreased baseline respiratory system compliance, whereas only allergic PGHS-1(-/-) mice showed increased baseline resistance and responsiveness to methacholine. Ovalbumin exposure caused a modest increase in lung PGHS-2 protein and a corresponding increase in BAL fluid PGE(2) in wild-type mice. We conclude that (a) PGHS-1 is the predominant enzyme that biosynthesizes PGE(2) in the normal mouse lung; (b) PGHS-1 and PGHS-2 products limit allergic lung inflammation and IgE secretion and promote normal lung function; and (c) airway inflammation can be dissociated from the development of airway hyperresponsiveness in PGHS-2(-/-) mice.

Allergens↗
PubMed1999

Pulmonary cholesterol granulomas in patients with pulmonary artery hypertension: chest radiographic and CT findings.

OBJECTIVE: We describe the chest radiographic and CT findings of pulmonary cholesterol granulomas in patients with pulmonary artery hypertension. CONCLUSION: Histopathologic evidence of cholesterol granulomas was found in five (25%) of 20 patients with severe pulmonary hypertension. In three of these five patients, the granulomas manifested on chest radiographs and CT as small centrilobular nodules mimicking the appearance of sarcoidosis, bronchiolitis, hypersensitivity pneumonitis, or aspiration.

Adult↗
PubMed1998

Ultrastructural features of diffuse malignant mesotheliomas.

The distinction of malignant mesothelioma from tumors metastatic to the serosal membranes can often be made based on the results of histochemical or immunohistochemical studies. However, in some cases, these techniques are inadequate to make a firm diagnosis. In these instances, electron microscopic studies with the observation of a constellation of characteristic ultrastructural findings may permit an unequivocal diagnosis of mesothelioma.

Adenocarcinoma↗
PubMed1998

The diagnosis of desmoplastic malignant mesothelioma and its distinction from fibrous pleurisy: a histologic and immunohistochemical analysis of 31 cases including p53 immunostaining.

We studied 31 patients with fibrotic pleural lesions and classified them as desmoplastic malignant mesothelioma (DMM) or fibrous pleurisy (FP) using predetermined histologic criteria, including a paucicellular fibrotic pleural lesion with a storiform pattern or the "patternless pattern " of Stout, plus 1 or more of the following: invasion of chest wall or lung, bland necrosis, frankly sarcomatoid areas, and distant metastases. Staining for p53 was performed in 22 cases. Follow-up was obtained on all cases and compared with the histologic diagnoses. For 24 cases, the consensus diagnosis was DMM; 19 of these displayed frankly sarcomatoid areas, 16 showed invasion, and 8, bland necrosis. Of the 24, 23 patients died of disease and 1 was alive with disease. The remaining 7 cases were classified as FP, and all were alive without disease. The concordance among 3 pathologists using the criteria was excellent. Staining for p53 was more common in DMM than in FP, but the difference was not statistically significant. The concordance in interpreting the p53 stains by the same 3 pathologists was moderate. The distinction between DMM and FP in a predominantly fibrotic pleural lesion can be made in most cases with adequate sampling and the use of specific criteria.

Aged↗
PubMed1997

Silica-induced pleural disease: an unusual case mimicking malignant mesothelioma.

A 57-year-old man with a history of exposure to silica for 32 years presented with pleural thickening of the lower lobe of the left lung and a chronic right-sided pleural effusion without any radiographic evidence of parenchymal nodules in either lung. Light microscopic examination of a left visceral pleural biopsy specimen revealed markedly thickened pleura with fibrosis and macrophages containing birefringent silica and silicates. Occasional rounded intrapleural silicotic nodules were present. The underlying lung tissue did not show fibrosis or silicotic nodules. An energy-dispersive x-ray analysis confirmed the presence of silica. In the absence of lung involvement, this case represents a very unusual pathologic reaction caused by silica and silicates and adds to the clinical differential diagnosis of chronic pleuritis and malignant mesothelioma.

Diagnosis, Differential↗
PubMed1997

In vivo accumulation of iron on crocidolite is associated with decrements in oxidant generation by the fiber.

In vivo exposures to fibrous silicates are characterized by the formation of asbestos bodies. These structures consist of the original fiber with a coating of inexact composition, but it will include iron and protein. We tested the hypothesis that this iron, accumulated on asbestos bodies, participates in electron transport and oxidant generation. Thirty-day-old, male guinea pigs were intratracheally instilled with 1.0 mg crocidolite. Six months later, the animals were anesthetized, euthanized, and the fibers were isolated from the lungs. Energy-dispersive x-ray analysis and x-ray photoelectron spectroscopy confirmed an accumulation of metal onto the fiber after in vivo exposure. Stains for iron demonstrated a heterogeneous distribution of the metal on the silicate, while the uptake of a commercially available polyclonal antibody to ferritin localized to beaded enlargements along the coated fibers. Chelatable [Fe3+] associated with the fiber increased after in vivo exposure. However, oxidant generation by asbestos bodies was decreased relative to uncoated fibers despite the elevation in the concentration of metal associated with the crocidolite. We conclude that iron is accumulated onto fibers in the lungs of guinea pigs. Some portion of this accumulation of iron is in the form of ferritin, and this metal is not chemically reactive in oxidant production. Asbestos bodies may represent a successful attempt by the host to sequester the metal adsorbed to the surface of a fiber and diminish the oxidative challenge introduced by a fibrous silicate. Subsequently, the generation of free radicals by the fibrous silicate is diminished.

Animals↗
PubMed1997

Pleural macrophage recruitment and activation in asbestos-induced pleural injury.

The pathogenesis of asbestos-induced pleural fibrosis is poorly understood. Moreover, there has been a long-standing controversy regarding the relative potential of different commercial types of asbestos to cause pleural disease. We postulated that inhaled asbestos fibers translocate to the pleural space where they stimulate the recruitment and activation of pleural macrophages. To test this hypothesis, and to determine whether there are differences between inhaled amphibole and serpentine asbestos, Fischer 344 rats were exposed by intermittent inhalation (6 hr/day for 5 days/week over 2 weeks) to either National Institute of Environmental Health Sciences (NIEHS) crocidolite (average concentration 7.55 mg/m3) or NIEHS chrysotile fibers (average concentration 8.51 mg/m3). Comparisons were made with sham-exposed rats. The rats were sacrificed at 1 and 6 weeks after the cessation of exposure. More pleural macrophages were recovered at 1 and 6 weeks after crocidolite and chrysotile exposure than after sham exposure. Small numbers of crocidolite fibers (approximately 1 per 4000 cells) were detected in the pleural cell pellet of one crocidolite-exposed rat by scanning electron microscopy. Pleural macrophage supernatants were assayed for production of nitric oxide (NO) (by the Griess reaction) and tumor necrosis factor alpha (TNF-alpha) (by an enzyme-linked immunosorbent assay method). Significantly greater amounts of NO as well as TNF-alpha were generated by pleural macrophages at 1 and 6 weeks after either crocidolite or chrysotile inhalation than after sham exposure. Conceivably, translocation of asbestos fibers to the pleural space may provide a stimulus for persistent pleural space inflammation, cytokine production, and the generation of toxic oxygen and nitrogen radicals. Enhanced cytokine secretion within the pleural space may in turn upregulate adhesion molecule expression and the synthesis of extracellular matrix constituents by pleural mesothelial cells. Thus, our findings may have significance for the development of asbestos-induced pleural injury.

Animals↗
PubMed1997

Effect of erionite on the pleural mesothelium of the Fischer 344 rat.

OBJECTIVE: This study sought to assess the fibrogenic and carcinogenic potential of erionite (a fibrous zeolite) on the pleural mesothelium of the Fischer 344 rat (n = 24). DESIGN: The study was designed to examine rat pleural mesothelial changes by three independent observers at timed intervals, ranging from 1 to 480 days postinoculation using erionite from the Pine Valley, Nevada (USA) area. The mean length and width of the erionite fibers were 2.29 and 0.48 microns, respectively. Only microscopic observations made by majority (2/3) or unanimity (3/3) were accepted for final diagnosis. RESULTS: Pleural and lung tissue were available for examination in 21 of the 24 rats. Fibrosis, chronic inflammation, and foreign body reaction occurred in 6 of 21 rats. Mesothelial hyperplasia and dysplasia occurred in 9 and 3 of the 21 rats, respectively. A single mesothelioma was identified at 434 days in a rat that had gross nodular pleural lesions. CONCLUSIONS: The findings reported herein confirm the strong fibrogenic potential of erionite but are at variance with previous studies reporting much higher yields of mesothelioma. The reasons for the low yield of mesothelioma in this study are not known, but may be related to the study design, the strict criteria used for histopathologic diagnosis, and/or possible differences in erionite physicochemical properties, associated with its geographic distribution, most previous animal studies having used erionite from the Rome, Oregon (USA) area.

Animals↗
PubMed1997

Iron accumulation in lung allografts after transplantation.

Lung transplantation has become a therapeutic option for end-stage pulmonary diseases, but after transplantation, infections and obliterative bronchiolitis (OB) are major causes of long-term morbidity and mortality. OB is a fibroproliferative disease, of poorly understood etiology, characterized by an irreversible decline in allograft function. Because diseases with tissue iron overload are characterized by fibrosis and end-organ failure, we studied the iron concentrations in BAL fluid and lung tissue in 10 lung allograft patients. BAL fluid revealed significantly elevated iron concentrations in allograft patients compared with five normal volunteers (135+/-16.54 micromol/L vs 33.65+/-7.48 micromol/L, respectively). Prussian blue staining of biopsy specimens of lung allograft tissue revealed an accumulation of iron primarily in alveolar macrophages. Immunohistochemical stains for ferritin revealed accumulation of the protein in macrophages, interstitium, vascular walls, and bronchiolar epithelium. Iron studies of the blood (serum ferritin and iron concentrations) revealed no evidence for systemic iron overload. In conclusion, patients with pulmonary allografts appear to have elevated concentrations of iron in lung tissue. This iron overload may place the allografts at increased risk of metal-mediated injury and fibrosis.

Adult↗
PubMed1997

Prevalence of pulmonary atypical alveolar cell hyperplasia in an autopsy population: a study of 100 cases.

A precursor lesion of pulmonary adenocarcinoma has not been clearly defined. Previous studies suggested that atypical alveolar cell hyperplasia (AACH) might represent such a precursor lesion. Most previous studies showed an association between AACH and adenocarcinoma in surgical resection specimens. In this study, we searched for the prevalence of AACH and nonatypical alveolar cell hyperplasia (ACH) in a general autopsy population. Cases in which there was clinical or anatomic evidence of pulmonary neoplasia were excluded from the study. In the 100 consecutive autopsies examined, we found four cases of ACH and two cases of AACH. The two AACH lesions showed cytologic atypia and stained positively for p53 and c-erb-2. These findings suggest a possible role for AACH as a precursor lesion of adenocarcinoma of the lung.

Adenocarcinoma↗
PubMed1997

Malignant mesothelioma in women.

About 8% of our cases of mesothelioma occur in women, with a median age of 59 years. Our percentage is lower than other series reported in the literature because of the large number of occupationally exposed men referred to our laboratory. Tumor arose in the pleura in 86% of the women in our study, and the majority were epithelial. Pleural plaques were found in half of the women for which this information was available, and asbestosis was found in only 16%. A history of exposure to asbestos was identified in three quarters of the women, more than half of whom were household contacts of asbestos workers. Occupational exposure to asbestos was identified in only 19% of patients. An elevated tissue asbestos burden was noted in 70% of women from whom lung tissue was available for analysis. The main fiber type identified was amosite, followed by tremolite and chrysotile. These findings and those from other countries suggest a need for reassessment of the background rate of mesothelioma in industrialized nations.

Adult↗
PubMed1996

Lipopolysaccharide up-regulates platelet-derived growth factor (PDGF) alpha-receptor expression in rat lung myofibroblasts and enhances response to all PDGF isoforms.

Differential expression of PDGF receptor alpha and beta subunits controls the response of mesenchymal cells to the three PDGF isoforms (AA, AB, and BB). Cultured rat lung myofibroblasts (RLMF) possess abundant PDGF receptor-beta (PDGF-Rbeta) and little PDGF receptor-alpha (PDGF-Ralpha). Here we show that LPS up-regulates expression of PDGF-Ralpha and increases the sensitivity of RLMF to all three PDGF isoforms. Treatment of RLMF for 4 to 48 h with LPS enhanced PDGF-Ralpha surface expression and mRNA 5- to 10-fold but caused no change in expression of PDGF-Rbeta. Both RNA and protein synthesis were necessary for up-regulation of PDGF-Ralpha, and the increase in PDGF-Ralpha mRNA was most likely regulated at the transcriptional level. PDGF-Ralpha up-regulation was not mediated by the IL-1R system and was independent of LPS-binding proteins in serum. Highly confluent cultures of RLMF responded more strongly to LPS than did subconfluent cultures. LPS treatment enhanced the mitogenic and chemotactic responses of RLMF to all PDGF isoforms at least threefold. We postulate that signal transduction by PDGF-receptor alphabeta heterodimers was important in the enhanced responses to PDGF-AB and -BB. We propose that regulation of PDGF-Ralpha is a critical event in the genesis of pulmonary fibroproliferative diseases.

Animals↗
PubMed1996

p53 and MDM2 immunostaining in pulmonary blastomas and bronchogenic carcinomas.

Pulmonary blastomas (PBs) are rare primary malignancies that include adult types: biphasic pulmonary blastoma (BPB) and well-differentiated fetal adenocarcinoma (WDFA); and childhood type: pleuropulmonary blastoma (PPB). Their pathogenesis and relationship to bronchogenic carcinoma (BCA) are controversial. To determine whether or not PB share molecular pathological features with BCA, the authors immunostained three BPB, three WDFA, three PPB, and 80 standard BCA for p53 protein and MDM2 protein, gene products believed to be significant in the pathogenesis of BCA. Paraffin-embedded tissue sections were immunostained with monoclonal antibody to p53 and MDM2 proteins. Strong intranuclear staining in greater than 10% of cells was considered positive. Three (50%) BPB and WDFA stained for p53 and five (83%) for MDM2. None of the PPB stained for p53, and one PPB did not stain for either p53 or MDM2. Five of six adult type PB occurred in smokers, whereas none of the PPB was associated with smoking. Seventy-five (94%) of the BCA stained for MDM2 and 46 (61%) for p53. Immunostaining patterns for p53 and MDM2 in adult types of PB, and not PPB, appear similar to those for BCA. This may suggest that adult type PB, but not childhood PB, have a similar pathogenesis to BCA.

Adenocarcinoma↗
PubMed1996

Composition of lung lavage in pulmonary alveolar microlithiasis.

A case of pulmonary alveolar microlithiasis (PAM) is reported wherein total lung lavage was performed for relief of dyspnea. Characterization of the lavage material and examination of the microliths isolated from the lavage fluid confirmed previous reports of their spherical-ovoid shape and a 2:1 calcium to phosphate composition. The microliths contained considerable amounts of ionizable iron and generated oxidants in an in vitro system. A detailed biochemical analysis of the lavage fluid reflected elevations in total protein, phosphatidylserine, phosphatidylglycerol and the ratio of phosphatidylglycerol to phosphatidylinositol. Surfactant apoprotein-A levels approximated that of normal patients. The potential roles of oxidant generation and alterations in surfactant metabolism are discussed in the context of the pathogenesis of PAM.

Adult↗
PubMed1996

Glutathione depletion in epithelial lining fluid of lung allograft patients.

The lower respiratory tract is protected against reactive oxygen species (ROS) by a complex antioxidant system. In the epithelial lining fluid (ELF), glutathione (L-alpha-glutamyl-L-cysteinylglycine, GSH) is essential for adequate protection of pneumocytes from potential toxicity mediated by extracellular hydrogen peroxide (H2O2). We assessed the concentration of total GSH in bronchoalveolar lavage fluid (BALF) in lung allograft patients in the absence and presence of acute rejection. Bronchoalveolar lavage (BAL) and biopsies were performed concurrently on 36 occasions in 17 patients who had undergone lung transplantation. BALF samples were divided into two groups on the basis of presence or absence of acute lung rejection on transbronchial biopsy. Seven BALF samples were obtained from control subjects for comparison. The BALF data demonstrated significantly lymphocyte recruitment and evidence of lung injury during acute rejection episodes. Transplant allografts without rejection showed significant depletion of total GSH in the ELF as compared with that of normal volunteers (94.0 +/- 9.7 microM versus 302.6 +/- 40.8 microM, p < 0.01). Transplant allografts with acute rejection had a slightly higher GSH concentration in their ELF (179.8 +/- 34.7), but this was still lower than control values. The deficiency of total GSH in the alveolar fluid may predispose lung allografts to extracellular H2O2-mediated toxicity.

Adult↗
PubMed1996

Pulmonary fibrogenesis after three consecutive inhalation exposures to chrysotile asbestos.

Previously, this laboratory developed a model of asbestos-induced pulmonary fibrogenesis in rats and mice after a brief (1 to 3-h) inhalation exposure. However, typical human environmental exposures would be repeated, although at lower concentrations than those used in our animal model. Here we have extended this model to encompass repeated exposures and consequent long-term effects. Groups of rats were exposed to chrysotile aerosol (10 mg/m3) for 3- to 5-h periods over 3 consecutive days. Lung fiber burden and pathologic features were studied for as long as 6 mo after exposure. We found that many of the longest (> or = 8 microm) fibers were retained in the lung for at least 6 mo, whereas shorter fibers were cleared more rapidly. The three exposures to chrysotile caused a large increase in DNA synthesis in the epithelium of terminal bronchioles and more proximal airways. When compared with a single exposure, the triple exposure caused an enhanced inflammatory response as well as a prolonged period of increased DNA synthesis in the proximal alveolar region. Hyperplastic, fibrotic lesions subsequently developed in the same region and persisted for at least 6 mo after exposure. These findings will be valuable in directing future studies of the mechanisms of pulmonary fibrosis in this model.

Administration, Inhalation↗