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International Journal of Molecular... Nov 2022Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in... (Review)
Review
Cathepsin K (CatK) is a part of the family of cysteine proteases involved in many important processes, including the degradation activity of collagen 1 and elastin in bone resorption. Changes in levels of CatK are associated with various pathological conditions, primarily related to bone and cartilage degradation, such as pycnodysostosis (associated with CatK deficiency), osteoporosis, and osteoarthritis (associated with CatK overexpression). Recently, the increased secretion of CatK is being highly correlated to vascular inflammation, hypersensitivity pneumonitis, Wegener granulomatosis, berylliosis, tuberculosis, as well as with tumor progression. Due to the wide spectrum of diseases in which CatK is involved, the design and validation of active site-specific inhibitors has been a subject of keen interest in pharmaceutical companies in recent decades. In this review, we summarized the molecular background of CatK and its involvement in various diseases, as well as its clinical significance for diagnosis and therapy.
Topics: Cathepsin K; Collagen Type I; Bone and Bones; Cysteine Proteases
PubMed: 36430239
DOI: 10.3390/ijms232213762 -
Postgraduate Medical Journal Jul 1988The increasing use of beryllium in a variety of industries continues to be a hazard. New cases are still being reported to the UK Beryllium Case Registry, now numbering... (Review)
Review
The increasing use of beryllium in a variety of industries continues to be a hazard. New cases are still being reported to the UK Beryllium Case Registry, now numbering 60 in the period 1945-1988. The majority of cases follow inhalation which results in acute beryllium disease (chemical pneumonitis) or more commonly chronic beryllium disease--a granulomatous pneumonitis. Granulomatous skin nodules also occur following local implantation. The clinical and radiological features are briefly described with the emphasis on pathology and immunology. Laser microprobe mass spectrometry analysis of tissue sections is a major advance in diagnosis. Detection of beryllium distinguishes the granulomas of chronic beryllium disease from other diseases, in particular sarcoidosis. The role of beryllium lymphocyte transformation tests is discussed. Chronic beryllium disease is steroid dependent and local excision of skin lesions appears to be curative. There is no evidence that beryllium is carcinogenic.
Topics: Berylliosis; Humans; Skin Diseases
PubMed: 3074283
DOI: 10.1136/pgmj.64.753.511 -
Occupational and Environmental Medicine Feb 2022Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually...
OBJECTIVES
Human leukocyte antigen-DP beta 1 (HLA-DPB1) with a glutamic acid at the 69th position of the ß chain (E69) genotype and inhalational beryllium exposure individually contribute to risk of chronic beryllium disease (CBD) and beryllium sensitisation (BeS) in exposed individuals. This retrospective nested case-control study assessed the contribution of genetics and exposure in the development of BeS and CBD.
METHODS
Workers with BeS (n=444), CBD (n=449) and beryllium-exposed controls (n=890) were enrolled from studies conducted at nuclear weapons and primary beryllium manufacturing facilities. Lifetime-average beryllium exposure estimates were based on workers' job questionnaires and historical and industrial hygienist exposure estimates, blinded to genotype and case status. Genotyping was performed using sequence-specific primer-PCR. Logistic regression models were developed allowing for over-dispersion, adjusting for workforce, race, sex and ethnicity.
RESULTS
Having no E69 alleles was associated with lower odds of both CBD and BeS; every additional E69 allele increased odds for CBD and BeS. Increasing exposure was associated with lower odds of BeS. CBD was not associated with exposure as compared to controls, yet the per cent of individuals with CBD versus BeS increased with increasing exposure. No evidence of a gene-by-exposure interaction was found for CBD or BeS.
CONCLUSIONS
Risk of CBD increases with E69 allele frequency and increasing exposure, although no gene by environment interaction was found. A decreased risk of BeS with increasing exposure and lack of exposure response in CBD cases may be due to the limitations of reconstructed exposure estimates. Although reducing exposure may not prevent BeS, it may reduce CBD and the associated health effects, especially in those carrying E69 alleles.
Topics: Berylliosis; Beryllium; Case-Control Studies; Chronic Disease; Female; Genotype; HLA-DP beta-Chains; Humans; Male; Occupational Exposure; Polymorphism, Genetic; Retrospective Studies
PubMed: 34535537
DOI: 10.1136/oemed-2021-107736 -
Frontiers in Immunology 2020Pulmonary sarcoidosis and chronic beryllium disease (CBD) are inflammatory granulomatous lung diseases defined by the presence of non-caseating granulomas in the lung.... (Review)
Review
Pulmonary sarcoidosis and chronic beryllium disease (CBD) are inflammatory granulomatous lung diseases defined by the presence of non-caseating granulomas in the lung. CBD results from beryllium exposure in the workplace, while the cause of sarcoidosis remains unknown. CBD and sarcoidosis are both immune-mediated diseases that involve Th1-polarized inflammation in the lung. Beryllium exposure induces trafficking of dendritic cells to the lung in a mechanism dependent on MyD88 and IL-1α. B cells are also recruited to the lung in a MyD88 dependent manner after beryllium exposure in order to protect the lung from beryllium-induced injury. Similar to most immune-mediated diseases, disease susceptibility in CBD and sarcoidosis is driven by the expression of certain MHCII molecules, primarily in CBD and several alleles in sarcoidosis. One of the defining features of both CBD and sarcoidosis is an infiltration of activated CD4+ T cells in the lung. CD4+ T cells in the bronchoalveolar lavage (BAL) of CBD and sarcoidosis patients are highly Th1 polarized, and there is a significant increase in inflammatory Th1 cytokines present in the BAL fluid. In sarcoidosis, there is also a significant population of Th17 cells in the lungs that is not present in CBD. Due to persistent antigen exposure and chronic inflammation in the lung, these activated CD4+ T cells often display either an exhausted or anergic phenotype. Evidence suggests that these T cells are responding to common antigens in the lung. In CBD there is an expansion of beryllium-responsive TRBV5.1+ TCRs expressed on pathogenic CD4+ T cells derived from the BAL of CBD patients that react with endogenous human peptides derived from the plexin A protein. In an acute form of sarcoidosis, there are expansions of specific TRAV12-1/TRBV2 T cell receptors expressed on BAL CD4+ T cells, indicating that these T cells are trafficking to and expanding in the lung in response to common antigens. The specificity of these pathogenic CD4+T cells in sarcoidosis are currently unknown.
Topics: Adaptive Immunity; Animals; Berylliosis; Chronic Disease; HLA-DP beta-Chains; Humans; Lung; Sarcoidosis, Pulmonary; T-Lymphocyte Subsets; T-Lymphocytes
PubMed: 32256501
DOI: 10.3389/fimmu.2020.00474 -
British Medical Journal May 1956
Topics: Berylliosis; Humans; Poisoning
PubMed: 13316118
DOI: No ID Found -
Proceedings of the Royal Society of... Mar 1955
Topics: Berylliosis; Humans; Poisoning
PubMed: 14371570
DOI: No ID Found -
Current Opinion in Immunology Dec 2013Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by a hypersensitivity to beryllium and characterized by the accumulation of beryllium-specific... (Review)
Review
Chronic beryllium disease (CBD) is a granulomatous lung disorder caused by a hypersensitivity to beryllium and characterized by the accumulation of beryllium-specific CD4(+) T cells in the lung. Genetic susceptibility to beryllium-induced disease is strongly associated with HLA-DP alleles possessing a glutamic acid at the 69th position of the β-chain (βGlu69). The structure of HLA-DP2, the most prevalent βGlu69-containing molecule, revealed a unique solvent-exposed acidic pocket that includes βGlu69 and represents the putative beryllium-binding site. The delineation of mimotopes and endogenous self-peptides that complete the αβTCR ligand for beryllium-specific CD4(+) T cells suggests a unique role of these peptides in metal ion coordination and the generation of altered self-peptides, blurring the distinction between hypersensitivity and autoimmunity.
Topics: Berylliosis; Beryllium; CD4-Positive T-Lymphocytes; Chronic Disease; Genetic Predisposition to Disease; Humans
PubMed: 23978481
DOI: 10.1016/j.coi.2013.07.012 -
CMAJ : Canadian Medical Association... Dec 2023
Topics: Humans; Middle Aged; Berylliosis; Metal Workers
PubMed: 38049163
DOI: 10.1503/cmaj.221680 -
Clinics in Chest Medicine Dec 1997Since sarcoidosis was first recognized as a distinct clinical entity, investigators have speculated that a transmissible agent may cause sarcoidosis. Recent attempts at... (Review)
Review
Since sarcoidosis was first recognized as a distinct clinical entity, investigators have speculated that a transmissible agent may cause sarcoidosis. Recent attempts at directly isolating infectious organisms or indirectly detecting microbial DNA or RNA from sarcoid tissue have led to inconclusive results. Studies on the immunopathogenic origins of sarcoidosis have provided evidence of persistent antigenic stimulation at sites of inflammation that are associated with dysregulated cytokine production. To date, however, the challenge of defining the cause of sarcoidosis remains unmet.
Topics: Autoimmune Diseases; Berylliosis; Environmental Exposure; Humans; Infections; Sarcoidosis
PubMed: 9413653
DOI: 10.1016/s0272-5231(05)70413-5 -
Respiratory Medicine Mar 2016Lymphadenopathy is a common radiological finding in many thoracic diseases and may be caused by a variety of infectious, inflammatory, and neoplastic conditions. This... (Review)
Review
Lymphadenopathy is a common radiological finding in many thoracic diseases and may be caused by a variety of infectious, inflammatory, and neoplastic conditions. This review aims to describe the patterns of mediastinal and hilar lymphadenopathy found in benign diseases in immunocompetent patients. Computed tomography is the method of choice for the evaluation of lymphadenopathy, as it is able to demonstrate increased size of individual nodes, abnormalities of the interface between the mediastinum and lung, invasion of surrounding fat, coalescence of adjacent nodes, obliteration of the mediastinal fat, and hypo- and hyperdensity in lymph nodes. Intravenous contrast enhancement may be needed to help distinguish nodes from vessels. The most frequent infections resulting in this finding are tuberculosis and fungal disease (particularly histoplasmosis and coccidioidomycosis). Sarcoidosis is a relatively frequent cause of lymphadenopathy in young adults, and can be distinguished from other diseases - especially when enlarged lymph nodes are found to be multiple and symmetrical. Other conditions discussed in this review are silicosis, drug reactions, amyloidosis, heart failure, Castleman's disease, viral infections, and chronic obstructive pulmonary disease.
Topics: Amyloidosis; Berylliosis; Castleman Disease; Coccidioidomycosis; Diagnosis, Differential; Drug Hypersensitivity; Heart Failure; Histoplasmosis; Humans; Idiopathic Pulmonary Fibrosis; Lung Diseases, Fungal; Lymph Nodes; Lymphadenitis; Lymphatic Diseases; Mediastinum; Pulmonary Disease, Chronic Obstructive; Pulmonary Embolism; Sarcoidosis; Silicosis; Thorax; Tomography, X-Ray Computed; Tuberculosis, Lymph Node; Virus Diseases
PubMed: 26860219
DOI: 10.1016/j.rmed.2016.01.021