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BioMed Research International 2015Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many... (Review)
Review
Antioxidant compounds such as glutathione and its enzymes have become the focus of attention of medical sciences. Glutathione, a specific tripeptide, is involved in many intercellular processes. The glutathione concentration is determined by the number of GAG repeats in gamma-glutamylcysteine synthetase. GAG polymorphisms are associated with an increased risk of schizophrenia, berylliosis, diabetes, lung cancer, and nasopharyngeal tumors. Cancer cells with high glutathione concentration are resistant to chemotherapy treatment. The oxidized form of glutathione is formed by glutathione peroxidases (GPXs). The changes in activity of GPX1, GPX2, and GPX3 isoforms may be associated with the development of cancers, for example, prostate cancer or even colon cancer. Detoxification of glutathione conjugates is possible due to activity of glutathione S-transferases (GSTs). Polymorphisms in GSTM1, GSTP1, and GSTO1 enzymes increase the risk of developing breast cancer and hepatocellular carcinoma. Gamma-glutamyl transpeptidases (GGTs) are responsible for glutathione degradation. Increased activity of GGT correlates with adverse prognosis in patients with breast cancer. Studies on genes encoding glutathione enzymes are continued in order to determine the correlation between DNA polymorphisms in cancer patients.
Topics: Genetic Predisposition to Disease; Genotype; Glutathione; Hematologic Neoplasms; Humans; Polymorphism, Genetic; Risk Factors
PubMed: 26682223
DOI: 10.1155/2015/853573 -
Environmental Health Perspectives Oct 1996This report is based on 30 deaths from chronic beryllium disease (CBD) in the United Kingdom with details of 19 autopsies. The majority were fluorescent lamp workers and... (Review)
Review
This report is based on 30 deaths from chronic beryllium disease (CBD) in the United Kingdom with details of 19 autopsies. The majority were fluorescent lamp workers and machinists who died from respiratory failure. There were no cases of lung cancer. The survival times ranged from less than 1 to 29 years and was longest in machinists. All of the workers showed interstitial pulmonary fibrosis with varying degrees of cystic change. The majority showed hyalinized, and a few active sarcoid-type, granulomas. Extrathoracic granulomas, as in a U.K. sarcoid autopsy series, were rare. A notable difference was the absence of myocardial involvement in CBD compared to an incidence of 20% in the sarcoid autopsies. The detection of beryllium in the criteria for diagnosis is emphasized and the cases classified as definite include 12 of 19 positive analysis, 6 of 19, negative or unavailable analysis. The remaining case was classified as dubious because, despite a positive analysis, granulomas were absent. The main differential diagnosis is sarcoidosis.
Topics: Autopsy; Berylliosis; Chronic Disease; Humans; Lung; Registries; United Kingdom
PubMed: 8933040
DOI: 10.1289/ehp.96104s5949 -
Medicina (Kaunas, Lithuania) Nov 2020Chronic beryllium disease (CBD) is a granulomatous disease that resembles sarcoidosis but is caused by beryllium. Clinical manifestations similar to those observed in... (Review)
Review
Chronic beryllium disease (CBD) is a granulomatous disease that resembles sarcoidosis but is caused by beryllium. Clinical manifestations similar to those observed in CBD have occasionally been reported in exposure to dusts of other metals. However, reports describing the clinical, radiographic, and pathological findings in conditions other than beryllium-induced granulomatous lung diseases, and detailed information on mineralogical analyses of metal dusts, are limited. A 51-year-old Japanese man with rapidly progressing nodular shadows on chest radiography, and a 10-year occupation history of underground construction without beryllium exposure, was referred to our hospital. High-resolution computed tomography showed well-defined multiple centrilobular and perilobular nodules, and thickening of the intralobular septa in the middle and lower zones of both lungs. No extrathoracic manifestations were observed. Pathologically, the lung specimens showed 5-12 mm nodules with dust deposition and several non-necrotizing granulomas along the lymphatic routes. X-ray analytical electron microscopy of the same specimens revealed aluminum, iron, titanium, and silica deposition in the lung tissues. The patient stopped smoking and changed his occupation to avoid further dust exposure; the chest radiography shadows decreased 5 years later. The radiological appearances of CBD and sarcoidosis are similar, although mediastinal or hilar lymphadenopathy is less common in CBD and is usually seen in the presence of parenchymal opacities. Extrathoracic manifestations are also rare. Despite limited evidence, these findings are similar to those observed in pneumoconiosis with a sarcoid-like reaction due to exposure to dust other than of beryllium. Aluminum is frequently detected in patients with pneumoconiosis with a sarcoid-like reaction and is listed as an inorganic agent in the etiology of sarcoidosis. It was also detected in our patient and may have contributed to the etiology. Additionally, our case suggests that cessation of dust exposure may contribute to improvement under the aforementioned conditions.
Topics: Berylliosis; Beryllium; Dust; Humans; Male; Middle Aged; Pneumoconiosis; Sarcoidosis
PubMed: 33266389
DOI: 10.3390/medicina56110630 -
The European Respiratory Journal Dec 1998The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility... (Review)
Review
The role of genetic factors has been hypothesized in the pathogenesis of a number of chronic inflammatory lung diseases. The genes of the major histocompatibility complex (MHC) locus on human chromosome 6 have been identified as important determinants in diseases caused both by inorganic and organic compounds such as beryllium, gold, acid anhydrides, isocyanates and grass pollens. Since many environmental factors are the determinants of the immunopathogenesis of asthma, pulmonary granulomatous disorders, hypersensitivity pneumonitis and fibrotic lung disorders, an understanding of the interaction between environmental factors is crucial to epidemiology, prevention and treatment of these disorders. Berylliosis is an environmental chronic inflammatory disorder of the lung caused by inhalation of beryllium dusts. A human leukocyte antigen class II marker (HLA-DP Glu69) has been found to be strongly associated with the disease. In in vitro studies, the gene has been shown to play a direct role in the immunopathogenesis of the disease. In human studies, the gene has been shown to confer increased susceptibility to beryllium in exposed workers, thus suggesting that HLA gene markers may be used as epidemiological probes to identify population groups at higher risk of environmental lung diseases, to identify environmental levels of lung immunotoxicants that would be safe for the entire population and to prevent disease risk associated with occupation, manufactured products and the environment. Studies on the associations between human leukocyte antigens and chronic inflammatory lung disorders are reviewed in the context of the berylliosis model.
Topics: Animals; Berylliosis; Chronic Disease; Environmental Exposure; Genetic Predisposition to Disease; HLA Antigens; HLA-DP Antigens; Humans; Inflammation; Lung Diseases; Occupational Diseases
PubMed: 9877510
DOI: 10.1183/09031936.98.12061463 -
Respiratory Research Apr 2021Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single...
Sarcoidosis and chronic beryllium disease (CBD) are phenocopies, however the latter one has a clear trigger factor that is beryllium exposure. This study analyses single nucleotide polymorphisms (SNPs) in a large cohort for beryllium-exposed persons. SNPs were chosen for their relevance in sarcoidosis. Even though one of largest cohorts of beryllium-exposed persons was analysed, no statistically relevant association between any SNP and CBD could be verified. Notably, some SNPs exhibit inverse OR for beryllium sensitization and CBD with nominally statistical significance, which allows hypothesizing about pathophysiological role of genes for the disease triggering and development.
Topics: Berylliosis; Beryllium; Butyrophilins; Chronic Disease; DNA; Female; Humans; Male; Occupational Exposure; Polymorphism, Single Nucleotide
PubMed: 33863318
DOI: 10.1186/s12931-021-01691-2 -
Toxicology and Industrial Health Feb 2022Workers involved in crushing, milling, screening, and bagging of mica scrap are at increased risk to develop pneumoconiosis, a progressive material overloading of the...
Workers involved in crushing, milling, screening, and bagging of mica scrap are at increased risk to develop pneumoconiosis, a progressive material overloading of the lung that can lead to fibrosis and, in the later stages, to dyspnea. Pneumoconiosis is only seen after 10-20 years of respiratory mica exposure, and it can have a latency period of up to 40 years-today's cases date back to exposures during the second half of the 20 century. An occupational lifetime exposure level of 3 mg/m respirable mica dust has been considered to present no risk of pneumoconiosis since 1951 when the American Conference of Governmental Industrial Hygienists (ACGIH) established a 20 million particles per cubic foot (mppcf) (3.5 mg/m respirable particles) exposure limit. As a result, numbers of unspecified and other pneumoconioses in the United States have steadily declined since the early 1970s. Data from the National Institute for Occupational Safety and Health documents a 91% decrease between 1972 and 2014 (i.e., the peak of documented cases and the latest reported data) for combined cases of aluminosis, berylliosis, stannosis, siderosis, and fibrosis from production and use of bauxite, graphite fibers, wollastonite, cadmium, Portland cement, emery, kaolin, antimony, and mica. Ample evidence indicates that the 70-year-old occupational lifetime exposure level of 3 mg/m respirable mica dust is protective of workers' health.
Topics: Aged; Aluminum Silicates; Dust; Humans; Occupational Exposure; Pneumoconiosis
PubMed: 35230205
DOI: 10.1177/07482337211062281 -
Thorax Jan 1997Diffuse (interstitial) lung disease comprises a wide variety of conditions, individually relatively uncommon but collectively being found in approximately 50 per 100,000... (Review)
Review
Diffuse (interstitial) lung disease comprises a wide variety of conditions, individually relatively uncommon but collectively being found in approximately 50 per 100,000 population. Some of these diseases are of known aetiology but others are not. It has been suggested that the environment is a major contributory factor in this group of diseases. However, since not all individuals exposed to a common environment develop interstitial diseases, it can be hypothesised that there is a genetic predisposition to their development. These diseases cause major morbidity and mortality due to lung injury and fibrosis. It follows that, if individuals who are genetically predisposed to develop diseases characterised by lung injury and fibrosis can be identified, then management strategies can be designed which will attempt to identify and treat early disease and, in the longer term, to develop targeted genetic interventional approaches to treatment.
Topics: Adult; Berylliosis; Female; HLA-D Antigens; Humans; Lung Diseases, Interstitial; Male; Sarcoidosis; Scleroderma, Systemic
PubMed: 9039244
DOI: 10.1136/thx.52.1.92 -
American Journal of Respiratory and... Oct 2020A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells...
A subpopulation of B cells (age-associated B cells [ABCs]) is increased in mice and humans with infections or autoimmune diseases. Because depletion of these cells might be valuable in patients with certain lung diseases, the goal was to find out if ABC-like cells were at elevated levels in such patients. To measure ABC-like cell percentages in patients with lung granulomatous diseases. Peripheral blood and BAL cells from patients with sarcoidosis, beryllium sensitivity, or hypersensitivity pneumonitis and healthy subjects were analyzed for the percentage of B cells that were ABC-like, defined by expression of CD11c, low levels of CD21, FcRL 1-5 (Fc receptor-like protein 1-5) expression, and, in some cases, T-bet. ABC-like cells in blood were at low percentages in healthy subjects and higher percentages in patients with sarcoidosis as well as at high percentages among BAL cells of patients with sarcoidosis, beryllium disease, and hypersensitivity pneumonitis. Treatment of patients with sarcoidosis led to reduced percentages of ABC-like cells in blood. Increased levels of ABC-like cells in patients with sarcoidosis may be useful in diagnosis. The increase in percentage of ABC-like cells in patients with lung granulomatous diseases and decrease in treated patients suggests that depletion of these cells may be valuable.
Topics: Adult; Aged; Aged, 80 and over; Alveolitis, Extrinsic Allergic; B-Lymphocyte Subsets; Berylliosis; Bronchoalveolar Lavage Fluid; CD11c Antigen; Case-Control Studies; Female; Humans; Male; Membrane Proteins; Middle Aged; Receptors, Cell Surface; Receptors, Complement 3d; Receptors, Fc; Receptors, Immunologic; Sarcoidosis, Pulmonary; T-Box Domain Proteins; Young Adult
PubMed: 32501729
DOI: 10.1164/rccm.201911-2151OC -
Environmental Health Perspectives Oct 1996With the advent of in vitro immunologic testing, we can now detect exposed individuals who are sensitized to beryllium and those who have chronic beryllium disease (CBD)... (Review)
Review
With the advent of in vitro immunologic testing, we can now detect exposed individuals who are sensitized to beryllium and those who have chronic beryllium disease (CBD) with lung pathology and impairment. Earlier detection and more accurate diagnostic tools raise new questions about the natural history of sensitization and granulomatous disease. Preliminary data suggest that early detection identifies people who are sensitized to beryllium and that these individuals are at risk for progressing into clinical disease. This article discusses the historical, recent, and ongoing studies germane to our understanding of CBD natural history, including the immunologic and inflammatory basis of the disease, the environmental and host risk factors for disease progression, biological markers of disease severity and activity that may help predict outcome, and the implications for broad-based workplace screening to identify patients at the earliest stages of beryllium sensitization and disease.
Topics: Berylliosis; Beryllium; Chronic Disease; Humans
PubMed: 8933038
DOI: 10.1289/ehp.96104s5937 -
Toxicology Letters May 2022Dermal exposure to hazardous substances such as chemicals, toxics, metallic items and other contaminants may present substantial danger for health. Beryllium (Be) is a...
Dermal exposure to hazardous substances such as chemicals, toxics, metallic items and other contaminants may present substantial danger for health. Beryllium (Be) is a hazardous metal, especially when inhaled and/or in direct contact with the skin, associated with chronic beryllium disease (CBD) and Be sensitization (BeS). The objective of this study was to investigate the percutaneous penetration of beryllium and copper contained in metallic items as eyeglass temple tips (specifically BrushCAST® Copper Beryllium Casting Alloys containing Be 0.35 < 2.85%; Cu 95.3-98.7%), using Franz diffusion cells. This work demonstrated that the total skin absorption of Cu was higher (8.86%) compared to Be (4.89%), which was expected based on the high percentage of Cu contained in the eyeglass temple tips. However, Be accumulated significantly in the epidermis and dermis (up to 0.461 µg/cm) and, to a lesser extent, in the stratum corneum (up to 0.130 µg/cm) with a flux of permeation of 3.52 ± 4.5 µg/cm/hour and lag time of 2.3 ± 1.3 h, after cutaneous exposure of temple tip into 1.0 mL artificial sweat for 24 h. Our study highlights the importance of avoiding the use of Be alloys in items following long-term skin contact.
Topics: Alloys; Berylliosis; Beryllium; Copper; Eyeglasses; Humans
PubMed: 35427767
DOI: 10.1016/j.toxlet.2022.04.001