Beryllium
Berylliosis
HLA-DP Antigens
Fluorides
Air Pollutants, Occupational
Occupational Exposure
Metallurgy
Radioactive Pollutants
Probability Theory
Alloys
Chronic Disease
Mechanism of interaction of Acanthamoeba actophorin (ADF/Cofilin) with actin filaments. (1/202)
We characterized the interaction of Acanthamoeba actophorin, a member of ADF/cofilin family, with filaments of amoeba and rabbit skeletal muscle actin. The affinity is about 10 times higher for muscle actin filaments (Kd = 0.5 microM) than amoeba actin filaments (Kd = 5 microM) even though the affinity for muscle and amoeba Mg-ADP-actin monomers (Kd = 0.1 microM) is the same (Blanchoin, L., and Pollard, T. D. (1998) J. Biol. Chem. 273, 25106-25111). Actophorin binds slowly (k+ = 0.03 microM-1 s-1) to and dissociates from amoeba actin filaments in a simple bimolecular reaction, but binding to muscle actin filaments is cooperative. Actophorin severs filaments in a concentration-dependent fashion. Phosphate or BeF3 bound to ADP-actin filaments inhibit actophorin binding. Actophorin increases the rate of phosphate release from actin filaments more than 10-fold. The time course of the interaction of actophorin with filaments measured by quenching of the fluorescence of pyrenyl-actin or fluorescence anisotropy of rhodamine-actophorin is complicated, because severing, depolymerization, and repolymerization follows binding. The 50-fold higher affinity of actophorin for Mg-ADP-actin monomers (Kd = 0.1 microM) than ADP-actin filaments provides the thermodynamic basis for driving disassembly of filaments that have hydrolyzed ATP and dissociated gamma-phosphate. (+info)Exposure of cultured murine peritoneal macrophages to low concentrations of beryllium induces increases in intracellular calcium concentrations and stimulates DNA synthesis. (2/202)
Exposure of humans to beryllium dusts can induce a specific form of chronic pneumonitis that consists mainly of noncaseating granulomas in the lungs. Multiple studies have documented both genetic and immune components of chronic berylliosis. Much work has focused on T cells and their reactivity in berylliosis, but less work has focused on the end effector cells in granulomatous inflammation, macrophages. Because macrophages must become activated to form granulomas, and they become activated by responding to numerous immunomodulatory signals, we investigated the effects of beryllium (BeCl2) on a central signal transduction pathway in macrophages, increases in intracellular calcium ([Ca2+]i). Exposure of cultured murine peritoneal macrophages to low, nontoxic concentrations induced successive spikes or oscillations in [Ca2+]i. Concentrations as low as 5 nM induced significant increases in [Ca2+]i. The source of the increased [Ca2+]i was exclusively extracellular in that increases in [Ca2+]i could be completely blocked by chelating extracellular Ca2+, were inhibited by the Ca2+ channel blocker verapamil, and exposure of macrophages to BeCl2 had no effect on IP3 concentrations. DNA synthesis, a Ca2+-sensitive function, was enhanced in dividing 1LN cells and induced de novo in quiescent macrophages. Furthermore, BeCl2 enhanced DNA synthesis in the absence of coexposure to the protein kinase C activator phorbol myristate acetate. These data support the hypothesis that beryllium toxicity is in part the result of altered Ca2+ metabolism in mononuclear phagocytes consequent to reversible opening of plasma membrane channels. (+info)Identification of pathogenic T cells in patients with beryllium-induced lung disease. (3/202)
Chronic beryllium disease (CBD) is caused by beryllium exposure and is characterized by granulomatous inflammation with accumulation of CD4+ T cells in the lung. We analyzed TCR beta-chain and alpha-chain genes expressed by these CD4+ T cells. In the lungs of individual patients, as well as among four of five CBD patients studied, different oligoclonal expansions within the Vbeta3 subset were found to express homologous or even identical CDR3 amino acid sequences. These related expansions were specific for CBD patients, were compartmentalized to lung, and persisted at high frequency in patients with active disease. Limiting dilution cloning and analysis of coexpressed TCR alpha-chain genes confirmed that these TCRs were selectively expanded by a common Ag involving beryllium. Overall, homologous TCR beta- and alpha-chains showed identical V regions and invariant charged residues within the CDR3 but considerable variability in TCRJ usage. Remarkably, CBD patients expressing nearly identical TCRs did not share common HLA-DRB1 or DQ alleles. These results implicate particular CD4+ cells in the pathogenesis of CBD and provide insight into how beryllium is recognized in human disease. (+info)Partial IL-10 inhibition of the cell-mediated immune response in chronic beryllium disease. (4/202)
Chronic beryllium disease (CBD) provides a human disorder in which to study the delayed type IV hypersensitivity response to persistent Ag that leads to noncaseating pulmonary granuloma formation. We hypothesized that, in CBD, failure of IL-10 to modulate the beryllium-specific, cell-mediated immune response would result in persistent, maximal cytokine production and T lymphocyte proliferation, thus contributing to the development of granulomatous lung disease. To test this hypothesis, we used bronchoalveolar lavage cells from control and CBD subjects to evaluate the beryllium salt-specific production of endogenous IL-10 and the effects of exogenous human rIL-10 (rhIL-10) on HLA expression, on the production of IL-2, IFN-gamma, and TNF-alpha, and on T lymphocyte proliferation. Our data demonstrate that beryllium-stimulated bronchoalveolar lavage cells produce IL-10, and the neutralization of endogenous IL-10 does not increase significantly cytokine production, HLA expression, or T lymphocyte proliferation. Second, the addition of excess exogenous rhIL-10 partially inhibited the beryllium-stimulated production of IL-2, IFN-gamma, and TNF-alpha; however, we measured no change in T lymphocyte proliferation or in the percentage of alveolar macrophages expressing HLA-DP. Interestingly, beryllium salts interfered with an IL-10-stimulated decrease in the percentage of alveolar macrophages expressing HLA-DR. We conclude that, in the CBD-derived, beryllium-stimulated cell-mediated immune response, low levels of endogenous IL-10 have no appreciable effect; exogenous rhIL-10 has a limited effect on cytokine production and no effect on T lymphocyte proliferation or HLA expression. (+info)Chronic beryllium disease and cancer risk estimates with uncertainty for beryllium released to the air from the Rocky Flats Plant. (5/202)
Beryllium was released into the air from routine operations and three accidental fires at the Rocky Flats Plant (RFP) in Colorado from 1958 to 1989. We evaluated environmental monitoring data and developed estimates of airborne concentrations and their uncertainties and calculated lifetime cancer risks and risks of chronic beryllium disease to hypothetical receptors. This article discusses exposure-response relationships for lung cancer and chronic beryllium disease. We assigned a distribution to cancer slope factor values based on the relative risk estimates from an occupational epidemiologic study used by the U.S. Environmental Protection Agency (EPA) to determine the slope factors. We used the regional atmospheric transport code for Hanford emission tracking atmospheric transport model for exposure calculations because it is particularly well suited for long-term annual-average dispersion estimates and it incorporates spatially varying meteorologic and environmental parameters. We accounted for model prediction uncertainty by using several multiplicative stochastic correction factors that accounted for uncertainty in the dispersion estimate, the meteorology, deposition, and plume depletion. We used Monte Carlo techniques to propagate model prediction uncertainty through to the final risk calculations. We developed nine exposure scenarios of hypothetical but typical residents of the RFP area to consider the lifestyle, time spent outdoors, location, age, and sex of people who may have been exposed. We determined geometric mean incremental lifetime cancer incidence risk estimates for beryllium inhalation for each scenario. The risk estimates were < 10(-6). Predicted air concentrations were well below the current reference concentration derived by the EPA for beryllium sensitization. (+info)Characterization of the hinges of the effector loop in the reaction pathway of the activation of ras-proteins. Kinetics of binding of beryllium trifluoride to V29G and I36G mutants of Ha-ras-p21. (6/202)
This work experimentally confirms the pathway of activation of Ha-ras-p21, which was calculated by the method of Targeted Molecular Dynamics (TMD) (Diaz JF, Wroblowski B, Schlitter J, Engelborghs Y, 1997a, Proteins Struct Funct Genet 28:434-451). The process can be studied experimentally by analyzing the binding of BeF3- to the GDP complex of the active fluorescent mutant Y32W (Diaz JF, Sillen A, Engelborghs Y, 1997b, J Biol Chem 227:23138-23143). Two mutants, V29G and 136G, have been constructed at both sides of the effector loop of the active fluorescent mutant. This was done to check the proposed reaction pathway and to provide further insight into the mechanism of the activation of ras proteins. Both mutations accelerate the conformational isomerization with two orders of magnitude, demonstrating convincingly the role of these residues as hinges of the effector loop in one or more of the transitions of the conformational change. These results provide experimental support to the pathway calculated by TMD analysis. (+info)Aluminum fluoride inhibition of cabbage phospholipase D by a phosphate-mimicking mechanism. (7/202)
Aluminum fluoride (AlF(4)(-)) inhibited phospholipase D (PLD) purified from cabbage in both PIP(2)-dependent and PIP(2)-independent assays, consistent with its previously observed effect on mammalian PLD. The possibility that AlF(4)(-) may exert this effect through its known phosphate-mimicking property was examined. Inorganic phosphate, as well as two phosphate analogs, beryllium fluoride and orthovanadate, also inhibited cabbage PLD. Enzyme kinetic studies confirmed that PLD followed Hill kinetics, characteristic for allosteric enzymes, with an apparent Hill coefficient (n(app)) of 3.8, indicating positive cooperativity among multiple substrate-binding sites and suggesting possible functional oligomerization of the enzyme. AlF(4)(-) modification of PLD kinetics was consistent with a competitive mode of enzyme inhibition. It is therefore proposed that AlF(4)(-), and other phosphate analogs, inhibits plant PLD by competing with a substrate phosphate group for a substrate-binding site, thereby preventing the formation of an enzyme-phosphatidyl intermediate. This may be a conserved feature of PLD superfamily enzymes. (+info)Theoretical studies of metal-phosphate interactions: interaction of Li+, Na+, K+, Be++, Mg++, and Ca++ with H2PO4- and (CH3O)2PO2-: implications for nucleic acid solvation. (8/202)
Model phosphate-metal solvation complexes have been studied by ab-initio self-consistent-field techniques. The complexes studied include (RO)2PO2-(R = H or CH3) with Li+, Na+, K+, Be++, Mg++, Ca++, H2O, and Cl-. The geometries of the complexes were chosen to approximate reasonable model solvation complexes for phosphate groups in a nucleic acid environment. Calculated energies of formation vary as Be++ greater than Mg++ greater than Ca++ greater than Li+ greater than Na+ greater than K+ for all isostructural complexes, consistent with experimental binding trends. These results suggest that site binding of this type can successfully account for the relative specificities of ion binding in polynucleotides and other phosphate-containing molecules. (+info)Beryllium is a chemical element with the symbol Be and atomic number 4. It is a steel-gray, hard, brittle alkaline earth metal that is difficult to fabricate because of its high reactivity and toxicity. Beryllium is primarily used as a hardening agent in alloys, such as beryllium copper, and as a moderator and reflector in nuclear reactors due to its ability to efficiently slow down neutrons.
In the medical field, beryllium is most well-known for its potential to cause a chronic allergic lung disease called berylliosis. This condition can occur after prolonged exposure to beryllium-containing dusts or fumes, and can lead to symptoms such as cough, shortness of breath, and fatigue. In severe cases, it can cause scarring and thickening of the lung tissue, leading to respiratory failure.
Healthcare professionals should take appropriate precautions when handling beryllium-containing materials, including using protective equipment and following proper disposal procedures to minimize exposure.
Berylliosis is a chronic inflammatory disease that affects the lungs and, less commonly, other organs. It is caused by exposure to beryllium, a lightweight, strong metal used in various industries such as aerospace, electronics, and nuclear energy. The disease can be categorized into two types: acute and chronic.
Acute berylliosis is a rare form of the disease that occurs after high levels of exposure to beryllium, usually through inhalation. Symptoms typically develop within a few weeks to months after exposure and include cough, chest pain, shortness of breath, and fatigue. Acute berylliosis can be severe and may require hospitalization.
Chronic berylliosis, also known as beryllium sensitization or beryllium disease, is a more common form of the disease that occurs after long-term exposure to low levels of beryllium. It is characterized by the development of an immune response to beryllium, resulting in chronic inflammation and scarring of the lung tissue. Symptoms may not appear for several years after exposure and can include cough, shortness of breath, fatigue, weight loss, and joint pain.
Diagnosis of berylliosis typically involves a combination of medical history, physical examination, chest X-ray or CT scan, pulmonary function tests, and blood tests to detect the presence of beryllium sensitization. Treatment may include corticosteroids and other immunosuppressive medications to manage inflammation and scarring in the lungs. Avoiding further exposure to beryllium is essential to prevent disease progression.
HLA-DP beta-chains are proteins that are encoded by the HLA-DPB1 gene in humans. HLA, or Human Leukocyte Antigens, are a group of proteins found on the surface of cells that play an important role in the body's immune system. They help the body recognize and distinguish between its own cells and foreign substances such as viruses and bacteria.
HLA-DP beta-chains are one part of the HLA-DP complex, which is a type of MHC class II molecule. MHC class II molecules present pieces of proteins from outside the cell to T-cells, a type of white blood cell that plays a central role in the immune response. The HLA-DP complex is composed of an alpha and beta chain, and the beta-chain is encoded by the HLA-DPB1 gene.
Variations in the HLA-DPB1 gene can affect an individual's susceptibility to certain diseases, including autoimmune disorders and infectious diseases. Additionally, HLA-DP beta-chains can be used as markers for tissue typing in organ transplantation to help match donors and recipients and reduce the risk of rejection.
HLA-DP antigens are a type of human leukocyte antigen (HLA) class II molecule that plays a crucial role in the immune system. The HLAs are proteins found on the surface of cells that help the immune system distinguish between the body's own cells and foreign substances, such as viruses and bacteria.
The HLA-DP antigens are composed of two polypeptide chains, alpha and beta, which are encoded by genes located on chromosome 6 in the human genome. These antigens are expressed on the surface of various cells, including B lymphocytes, dendritic cells, and macrophages.
HLA-DP antigens present peptides to CD4+ T cells, which then become activated and help coordinate the immune response. The HLA-DP antigens have a wide range of peptide specificity, meaning they can bind and present a diverse array of peptides to the immune system.
Variation in HLA genes is common, and differences in these genes can affect an individual's susceptibility or resistance to various diseases, including autoimmune disorders, infectious diseases, and cancer. Therefore, understanding the role of HLA-DP antigens in the immune response is important for developing new therapies and treatments for a variety of medical conditions.
Fluorides are ionic compounds that contain the fluoride anion (F-). In the context of dental and public health, fluorides are commonly used in preventive measures to help reduce tooth decay. They can be found in various forms such as sodium fluoride, stannous fluoride, and calcium fluoride. When these compounds come into contact with saliva, they release fluoride ions that can be absorbed by tooth enamel. This process helps to strengthen the enamel and make it more resistant to acid attacks caused by bacteria in the mouth, which can lead to dental caries or cavities. Fluorides can be topically applied through products like toothpaste, mouth rinses, and fluoride varnishes, or systemically ingested through fluoridated water, salt, or supplements.
Occupational air pollutants refer to harmful substances present in the air in workplaces or occupational settings. These pollutants can include dusts, gases, fumes, vapors, or mists that are produced by industrial processes, chemical reactions, or other sources. Examples of occupational air pollutants include:
1. Respirable crystalline silica: A common mineral found in sand, stone, and concrete that can cause lung disease and cancer when inhaled in high concentrations.
2. Asbestos: A naturally occurring mineral fiber that was widely used in construction materials and industrial applications until the 1970s. Exposure to asbestos fibers can cause lung diseases such as asbestosis, lung cancer, and mesothelioma.
3. Welding fumes: Fumes generated during welding processes can contain harmful metals such as manganese, chromium, and nickel that can cause neurological damage and respiratory problems.
4. Isocyanates: Chemicals used in the production of foam insulation, spray-on coatings, and other industrial applications that can cause asthma and other respiratory symptoms.
5. Coal dust: Fine particles generated during coal mining, transportation, and handling that can cause lung disease and other health problems.
6. Diesel exhaust: Emissions from diesel engines that contain harmful particulates and gases that can cause respiratory and cardiovascular problems.
Occupational air pollutants are regulated by various government agencies, including the Occupational Safety and Health Administration (OSHA) in the United States, to protect workers from exposure and minimize health risks.
Aluminum compounds refer to chemical substances that are formed by the combination of aluminum with other elements. Aluminum is a naturally occurring metallic element, and it can combine with various non-metallic elements to form compounds with unique properties and uses. Some common aluminum compounds include:
1. Aluminum oxide (Al2O3): Also known as alumina, this compound is formed when aluminum combines with oxygen. It is a white, odorless powder that is highly resistant to heat and corrosion. Aluminum oxide is used in a variety of applications, including ceramics, abrasives, and refractories.
2. Aluminum sulfate (Al2(SO4)3): This compound is formed when aluminum combines with sulfuric acid. It is a white, crystalline powder that is highly soluble in water. Aluminum sulfate is used as a flocculant in water treatment, as well as in the manufacture of paper and textiles.
3. Aluminum chloride (AlCl3): This compound is formed when aluminum combines with chlorine. It is a white or yellowish-white solid that is highly deliquescent, meaning it readily absorbs moisture from the air. Aluminum chloride is used as a catalyst in chemical reactions, as well as in the production of various industrial chemicals.
4. Aluminum hydroxide (Al(OH)3): This compound is formed when aluminum combines with hydroxide ions. It is a white, powdery substance that is amphoteric, meaning it can react with both acids and bases. Aluminum hydroxide is used as an antacid and as a fire retardant.
5. Zinc oxide (ZnO) and aluminum hydroxide (Al(OH)3): This compound is formed when zinc oxide is combined with aluminum hydroxide. It is a white, powdery substance that is used as a filler in rubber and plastics, as well as in the manufacture of paints and coatings.
It's important to note that some aluminum compounds have been linked to health concerns, particularly when they are inhaled or ingested in large quantities. For example, aluminum chloride has been shown to be toxic to animals at high doses, while aluminum hydroxide has been associated with neurological disorders in some studies. However, the risks associated with exposure to these compounds are generally low, and they are considered safe for most industrial and consumer uses when used as directed.
Occupational exposure refers to the contact of an individual with potentially harmful chemical, physical, or biological agents as a result of their job or occupation. This can include exposure to hazardous substances such as chemicals, heavy metals, or dusts; physical agents such as noise, radiation, or ergonomic stressors; and biological agents such as viruses, bacteria, or fungi.
Occupational exposure can occur through various routes, including inhalation, skin contact, ingestion, or injection. Prolonged or repeated exposure to these hazards can increase the risk of developing acute or chronic health conditions, such as respiratory diseases, skin disorders, neurological damage, or cancer.
Employers have a legal and ethical responsibility to minimize occupational exposures through the implementation of appropriate control measures, including engineering controls, administrative controls, personal protective equipment, and training programs. Regular monitoring and surveillance of workers' health can also help identify and prevent potential health hazards in the workplace.
I'm sorry for any confusion, but "metallurgy" is not a term that has a medical definition. Metallurgy is a branch of materials science that deals with the properties, physical and chemical behavior, and production of metals. It involves studying the techniques and processes used to isolate, alloy, and fabricate various types of metal products. If you have any questions related to medicine or health, I'd be happy to try to help answer those for you!
Radioactive pollutants are defined as any harmful radioactive substances that are discharged into the environment and pose risks to human health and the ecosystem. These pollutants can be in the form of gases, liquids, or solids and can contaminate air, water, and soil. They originate from various sources such as nuclear power plants, medical facilities, industrial operations, and military activities.
Radioactive pollutants emit ionizing radiation, which can cause damage to living cells and DNA, leading to genetic mutations, cancer, and other health problems. Exposure to high levels of radioactivity can result in acute radiation sickness, including symptoms such as nausea, vomiting, diarrhea, and fever. Long-term exposure to low levels of radiation can increase the risk of developing cancer and other diseases over time.
Radioactive pollutants can also have negative impacts on the environment, contaminating soil and water and reducing biodiversity in affected areas. They can persist in the environment for long periods, making it difficult to clean up and remediate contaminated sites. Therefore, proper management and regulation of radioactive materials are essential to prevent their release into the environment and protect public health and the environment.
I'm sorry for any confusion, but "Probability Theory" is actually a branch of mathematics, not medicine. It provides a formal framework for quantifying and reasoning about uncertainty. It involves concepts such as random variables, probability distributions, expected values, and statistical inferences. While it is widely used in many scientific fields, including medical research, it is not a medical term itself.
'Alloys' is not a medical term. It is a term used in materials science and engineering to describe a mixture or solid solution composed of two or more elements, at least one of which is a metal. The components are typically present in significant amounts (>1% by weight). The properties of alloys, such as their strength, durability, and corrosion resistance, often differ from those of the constituent elements.
While not directly related to medicine, some alloys do have medical applications. For example, certain alloys are used in orthopedic implants, dental restorations, and other medical devices due to their desirable properties such as biocompatibility, strength, and resistance to corrosion.
A chronic disease is a long-term medical condition that often progresses slowly over a period of years and requires ongoing management and care. These diseases are typically not fully curable, but symptoms can be managed to improve quality of life. Common chronic diseases include heart disease, stroke, cancer, diabetes, arthritis, and COPD (chronic obstructive pulmonary disease). They are often associated with advanced age, although they can also affect children and younger adults. Chronic diseases can have significant impacts on individuals' physical, emotional, and social well-being, as well as on healthcare systems and society at large.