Interstitial pulmonary fibrosis and progressive massive fibrosis related to smoking methamphetamine with talc as filler.

We present a case of interstitial pulmonary fibrosis accompanied by radiographic evidence of progressive massive fibrosis in a patient who had a 15-20 year history of almost daily recreational inhalation of methamphetamine. Mineralogical analysis confirmed the presence of talc on biopsy of the area of progressive massive fibrosis. The coexistence of interstitial pulmonary fibrosis and progressive massive fibrosis suggests that prolonged recreational inhalation of methamphetamine that has been "cut" with talc can result in sufficient amount of talc being inhaled to result in interstitial pulmonary fibrosis and progressive massive fibrosis in the absence of other causes.

The influence of dust standards on the prevalence and severity of coal worker's pneumoconiosis at autopsy in the United States of America.

Context: Coal worker's pneumoconiosis is a major occupational lung disease in the United States. The disease is primarily controlled through reducing dust exposure in coal mines using technological improvements and through the establishment of dust standards by regulatory means.

Objective: To determine if dust standards established in the US Federal Coal Mine Health and Safety Act of 1969 have reduced the prevalence and severity of coal worker's pneumoconiosis.

Hybrid models identified a 12-gene signature for lung cancer prognosis and chemoresponse prediction.

Background: Lung cancer remains the leading cause of cancer-related deaths worldwide. The recurrence rate ranges from 35-50% among early stage non-small cell lung cancer patients. To date, there is no fully-validated and clinically applied prognostic gene signature for personalized treatment.

Role of oxidative/nitrosative stress-mediated Bcl-2 regulation in apoptosis and malignant transformation.

Bcl-2 is a key apoptosis regulatory protein of the mitochondrial death pathway. The oncogenic potential of Bcl-2 is well established, with its overexpression reported in various cancers. The antiapoptotic function of Bcl-2 is closely associated with its expression levels.

Perfluorooctane sulfonate (PFOS) induces reactive oxygen species (ROS) production in human microvascular endothelial cells: role in endothelial permeability.

Perfluorooctane sulfonate (PFOS) is a member of the perfluoroalkyl acids (PFAA) containing an eight-carbon backbone. PFOS is a man-made chemical with carbon-fluorine bonds that are among the strongest in organic chemistry, and PFOS is widely used in industry. Human occupational and environmental exposure to PFOS occurs globally.

Single- and multi-wall carbon nanotubes versus asbestos: are the carbon nanotubes a new health risk to humans?

Carbon nanotubes (CNT), since their discovery, have become one of the most promising nanomaterials in many industrial and biomedical applications. Due to their unique physicochemical properties, interest is growing in the manufacture of CNT-based products and their subsequent marketing. Since their discovery, the prospect of possible undesirable human health effects has been a focus of many scientific studies.

The role of p53 in silica-induced cellular and molecular responses associated with carcinogenesis.

Crystalline silica (silica), a suspected human carcinogen, produces an increase in reactive oxygen species (ROS) when fractured using mechanical tools used in several occupations. Although ROS has been linked to apoptosis, DNA damage, and carcinogenesis, the role of enhanced ROS production by silica in silica-induced carcinogenesis is not completely understood. The goal of this study was to compare freshly fractured and aged silica-induced molecular alterations in human immortalized/transformed bronchial epithelial cells (BEAS-IIB) and lung cancer cells with altered (H460) or deficient (H1299) p53 expression.

Titanium dioxide (TiO2) nanoparticles induce JB6 cell apoptosis through activation of the caspase-8/Bid and mitochondrial pathways.

Titanium dioxide (TiO(2)), a commercially important material, is used in a wide variety of products. Although TiO(2) is generally regarded as nontoxic, the cytotoxicity, pathogenicity, and carcinogenicity of TiO(2) nanoparticles have been recently recognized. The present study investigated TiO(2) nanoparticle-induced cell apoptosis and molecular mechanisms involved in this process in a mouse epidermal (JB6) cell line.

Effect of month-long treatment with oral N-acetylcysteine on the oxidative stress and proteinuria in patients with diabetic nephropathy: a pilot study.

Introduction: Oxidative stress plays an important role in the pathogenesis of diabetic nephropathy (DN). This study examined if use of N-acetylcysteine for a month in moderate doses would reduce the oxidative stress in patients with DN and reduce the proteinuria.

Methods: Fifteen volunteers with DN participated in the study.

DNA double-strand breaks by asbestos, silica, and titanium dioxide: possible biomarker of carcinogenic potential?

DNA double-strand breaks (DSBs) can result in cell death or genetic alterations when cells are subjected to radiation, exposure to toxins, or other environmental stresses. A complex DNA-damage-response pathway is activated to repair the damage, and the inability to repair these breaks can lead to carcinogenesis. One of the earliest responses to DNA DSBs is the phosphorylation of a histone, H2AX, at serine 139 (gamma-H2AX), which can be detected by a fluorescent antibody.

Pneumoconiosis from agricultural dust exposure among young California farmworkers.

Background: Agricultural workers are exposed to airborne pollutants, including organic and inorganic (mineral) dusts.

Objectives: Lung autopsy specimens from consecutive coroner's cases of Hispanic males in Fresno County, California, (n = 112) were obtained to determine whether mineral dust exposure in agricultural work leads to pneumoconiosis.

Methods: The left lung was fixed by inflation.

Contributions of dust exposure and cigarette smoking to emphysema severity in coal miners in the United States.

Rationale: Previous studies have shown associations between dust exposure or lung burden and emphysema in coal miners, although the separate contributions of various predictors have not been clearly demonstrated.

Objectives: To quantitatively evaluate the relationship between cumulative exposure to respirable coal mine dust, cigarette smoking, and other factors on emphysema severity.

Methods: The study group included 722 autopsied coal miners and nonminers in the United States.

Iron oxide nanoparticles induce human microvascular endothelial cell permeability through reactive oxygen species production and microtubule remodeling.

Background: Engineered iron nanoparticles are being explored for the development of biomedical applications and many other industry purposes. However, to date little is known concerning the precise mechanisms of translocation of iron nanoparticles into targeted tissues and organs from blood circulation, as well as the underlying implications of potential harmful health effects in human.

Results: The confocal microscopy imaging analysis demonstrates that exposure to engineered iron nanoparticles induces an increase in cell permeability in human microvascular endothelial cells.

Confirmation of gene expression-based prediction of survival in non-small cell lung cancer.

Purpose: It is a critical challenge to determine the risk of recurrence in early stage non-small cell lung cancer (NSCLC) patients. Accurate gene expression signatures are needed to classify patients into high- and low-risk groups to improve the selection of patients for adjuvant therapy.

Experimental Design: Multiple published microarray data sets were used to evaluate our previously identified lung cancer prognostic gene signature.

Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells.

Background: Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells.

Inflammation and lung cancer: roles of reactive oxygen/nitrogen species.

The lung is a highly specialized organ that facilitates uptake of oxygen and release of carbon dioxide. Due to its unique structure providing enormous surface area to outside ambient air, it is vulnerable to numerous pathogens, pollutants, oxidants, gases, and toxicants that are inhaled continuously from air, which makes the lung susceptible to varying degrees of oxidative injury. To combat these unrelenting physical, chemical, and biological insults, the respiratory epithelium is covered with a thin layer of lining fluid containing several antioxidants and surfactants.

Comparative cytotoxicity of cadmium and mercury in a human bronchial epithelial cell line (BEAS-2B) and its role in oxidative stress and induction of heat shock protein 70.

A number of toxic heavy metals, such as cadmium (Cd) and mercury (Hg), are widely used in occupational settings, and exposure to these metals is associated with the development of pulmonary diseases. Cytotoxicity, apoptosis, and reactive oxygen species (ROS) generation were tested to compare the biological reactivity of these two heavy metals using a human bronchial epithelial cell line, BEAS-2B. Further, heat-shock protein 70 (Hsp70) expression was observed as a sensitive indicator of cellular stress.

Comparative in vitro toxicity of grape- and citrus-farm dusts.

Agricultural workers are exposed to a variety of airborne dusts, including crystalline silica and other inorganic minerals. This study was designed to characterize the organic and inorganic components of agricultural dusts in California grape- and citrus-farm fields and to compare their cytotoxicity using in vitro toxicity bioassays as predictors of pathogenicity. Aerosolized dusts collected from farm fields were characterized by scanning-electron-microscopic energy-dispersive x-ray analysis, x-ray diffraction, trace metal analysis by plasma emission spectroscopy, and surface area measurements.

Comparative pathology of environmental lung disease: an overview.

Environmental factors play a major role in a majority of lung diseases. Asthma, chronic obstructive pulmonary disease (COPD), lung cancer, and many interstitial lung diseases are influenced or caused by environmental factors. Animals and humans may respond differently to the same agent, and a study of the comparative pathology between the two is useful for optimizing animal models of environmental lung disease and for evaluating their predictive value in carcinogenicity studies.

Nanoparticles: health effects--pros and cons.

With the advent of nanotechnology, the prospects for using engineered nanomaterials with diameters of < 100 nm in industrial applications, medical imaging, disease diagnoses, drug delivery, cancer treatment, gene therapy, and other areas have progressed rapidly. The potential for nanoparticles (NPs) in these areas is infinite, with novel new applications constantly being explored. The possible toxic health effects of these NPs associated with human exposure are unknown.

S-nitrosylation of Bcl-2 inhibits its ubiquitin-proteasomal degradation. A novel antiapoptotic mechanism that suppresses apoptosis.

Bcl-2 is a key apoptosis regulatory protein of the mitochondrial death pathway whose function is dependent on its expression levels. Although Bcl-2 expression is controlled by various mechanisms, post-translational modifications, such as ubiquitination and proteasomal degradation, have emerged as important regulators of Bcl-2 function. However, the underlying mechanisms of this regulation are unclear.

Diesel exhaust particles increase IL-1beta-induced human beta-defensin expression via NF-kappaB-mediated pathway in human lung epithelial cells.

Background: Human beta-defensin (hBD)-2, antimicrobial peptide primarily induced in epithelial cells, is a key factor in the innate immune response of the respiratory tract. Several studies showed increased defensin levels in both inflammatory lung diseases, such as cystic fibrosis, diffuse panbronchiolitis, idiopathic pulmonary fibrosis and acute respiratory distress syndrome, and infectious diseases. Recently, epidemiologic studies have demonstrated acute and serious adverse effects of particulate air pollution on respiratory health, especially in people with pre-existing inflammatory lung disease.

Respiratory burst: role in signal transduction in alveolar macrophages.

Alveolar macrophages play an important role in defense against airborne pathogens and particles. These macrophages respond through both the adaptive and acquired immune responses, and through the activation of a multitude of signaling pathways. One major macrophage defense mechanism is respiratory burst, the production of reactive oxygen species (ROS).