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PubMed1998

Chronic beryllium disease: uncommon disease, less common diagnosis.

Chronic beryllium disease (CBD) is typically considered only when occupational exposure to beryllium is a certainty; however, CBD has also occurred in occupational and environmental settings where exposure was unexpected. When the etiology of a case of granulomatous pulmonary disease is not determined, sarcoidosis is the "diagnosis of exclusion." This diagnosis does not communicate much information about the patient's prognosis, the disease's etiology, or even what disease etiologies were specifically excluded. Some cases of CBD have been called sarcoidosis, allowing exposure to continue for the patient and (at times) other individuals. The granulomatous changes of sarcoidosis are thought to result from an abnormal immune response. While the etiologic agents that can initiate this response are largely unknown, the immunopathogenesis of CBD has been well described, and laboratory methods are available in a few centers that can (if used) identify beryllium hypersensitivity. The potential for exposure and disease to be widely separated in time and location makes it important for health-care and environmental health professionals to be aware of these new diagnostic methods.

Berylliosis↗

PubMed2003

The beryllium "double standard" standard.

Brush Wellman, the world's leading producer and supplier of beryllium products, has systematically hidden cases of beryllium disease that occurred below the threshold limit value (TLV) and lied about the efficacy of the TLV in published papers, lectures, reports to government agencies, and instructional materials prepared for customers and workers. Hypocritically, Brush Wellman instituted a zero exposure standard for corporate executives while workers and customers were told the 2 microgram standard was "safe." Brush intentionally used its workers as "canaries for the plant," and referred to them as such. Internal documents and corporate depositions indicate that these actions were intentional and that the motive was money. Despite knowledge of the inadequacy of the TLV, Brush has successfully used it as a defense against lawsuits brought by injured workers and as a sales device to provide reassurance to customers. Brush's policy has reaped an untold number of victims and resulted in mass distribution of beryllium in consumer products. Such corporate malfeasance is perpetuated by the current market system, which is controlled by an organized oligopoly that creates an incentive for the neglect of worker health and safety in favor of externalizing costs to victimized workers, their families, and society at large.

Air Pollutants, Occupational↗

PubMedDate not supplied

Immune mechanisms in beryllium lung disease.

The role of the immune system in the pathogenesis of beryllium lung disease has been suspected for years. The observation of cutaneous hypersensitivity to beryllium led to the development of the lymphocyte blast transformation test; the test clearly distinguishes between healthy subjects, who show little or no blast transformation response, and patients with beryllium lung disease, who demonstrate significant responses. The degree of blast transformation also correlates with the severity of the clinical disease. Animal studies have demonstrated the importance of histocompatibility antigens in development of the disease, and support the participation of cellular immune mechanisms.

Animals↗

PubMed2000

[Assessment of occupational exposure to beryllium and its compounds].

The results of measurements of beryllium (Be) concentrations in the air of the 13 selected workplaces in 4 plants are presented. For the determination of beryllium, an agent carcinogenic to humans, atomic absorption spectrometry with graphite tubes was used. The method allows for determining 1 ng Be in 1 ml of the solution, which correspondents to 0.01 (microgram/m3 (for the sample solution volume--10 ml and the air volume--1000 l) or 0.05 (microgram/m3 (for the air volume--200 l). A personal or stationary sampling was used to collect Be on a membrane filter. The results of the measurements show that the exposure to beryllium in the work environment is not significant. Only in few cases Be exceeded trace amounts, and even then its concentrations were not higher than 1/50-1/10 of the Polish MAC values. Higher Be concentrations were found in the workplace air only during castings operations (up to 1/3 of MAC or 1/10 MAC-STEL).

Berylliosis↗

PubMed1975

Contact sensitivity in vitro. II. The effect of beryllium preparations on the proliferative responses of specifically allergised lymphocytes and normal lymphocytes stimulated with PHA.

Beryllium in various physical forms was studied for its ability to induce increased 14C-thymidine incorporation by allergised guinea pig lymphocytes. No increase was observed. It was further shown that beryllium had an inhibitory effect on the response of normal lymphocytes to PHA and on the response of allergised lymphocytes to antigen. These results support the finding in other systems that beryllium can suppress DNA synthesis.

Animals↗

PubMed1975

[Effect of a beryllium complex on growth of Pseudomonas fluorescens (types R and S). I. Influence on the lag phase].

The toxicity of beryllium for Pseudomonas fluorescens is studied with the aid of an anionic complex of the element which is stable in peptone medium at pH 6 during the period of investigation. The toxic effect is characterized by an increase in the lag phase which is proportional to the square of the beryllium concentration. Further, a process of progressive adaptation is observed when the concentration of the beryllium complex is gradually increased.

Beryllium↗

PubMed1990

The clinical significance of beryllium.

The carcinogenicity of beryllium for the human organism by inhalation has been established. Biochemical properties of this strong carcinogenic element are related to its intake, transport and accumulation in the body, as well as to cell division, DNA synthesis, enzyme inhibition, and gene expression. Other biochemical properties of beryllium are associated with its adjuvant action. Diagnosis and possible treatment of beryllium toxicity are also outlined.

Adjuvants, Immunologic↗

PubMed1989

Laser microprobe mass spectrometry (LAMMS) analysis of beryllium, sarcoidosis and other granulomatous diseases.

Beryllium was detected in the granulomas of all thirty-three cases of CBD examined and was absent in thirty cases of sarcoidosis. It was also found in association with coal dust in one of twelve normal lungs. Beryllium could also be detected in Schaumann bodies and hyalinized scars. Beryllium, though sometimes present in Kveim negative biopsies of CBD patients, was not found in any originating Kveim antigen. Rare earths (La, Ce, Pr and Nd) were unexpectedly found in two of the thirty sarcoid patients but not in any other samples. We have identified the crystalline component of Schaumann bodies as calcite and shown that they, as well as calispherules of microlithiasis, contain calcium phosphate. Al and Ti may be found in normal lungs but when associated with hypersensitivity granulomatous disease, their oxides were also present.

Berylliosis↗

PubMed1989

A canine model of beryllium-induced granulomatous lung disease.

Groups of beagle dogs were exposed by inhalation to attain either low or high initial lung burdens (ILB) of BeO calcined at 500 degrees or 1000 degrees C. Dogs were killed at 8, 32, 64, 180, and 365 days after exposure for evaluation of beryllium tissue burdens and histopathologic examination. Histologic lesions were characterized by perivascular and peribronchiolar infiltrates of lymphocytes and macrophages 8 days after exposure. These lesions progressed to distinct microgranulomas accompanied by patchy granulomatous pneumonia. Lesions were more severe in dogs exposed to 500 degrees C BeO. Additional dogs were sampled by bronchoalveolar lavage at 3, 6, 7, 11, 15, 18, and 22 months after exposure for characterization of lung cytology and lung immune responses. Lymphocyte percentages and numbers were increased in lavage samples 3 months after exposure in dogs with both the high and low ILB of 500 degrees C. Values for both parameters decreased rapidly thereafter. Dogs with either low or high ILB of 1000 degrees C-treated BeO displayed negligible to low and variable changes in both lymphocyte percentages and numbers. In vitro lymphocyte stimulation by beryllium was increased 180 and 210 days after exposure in dogs with the high ILB 500 degrees C BeO only. A marked degree of individual variation in both histologic lesions and lymphocyte responses among dogs was noted. Less soluble 1000 degrees C-treated BeO was retained in the lung longer than the more soluble 500 degrees C-treated material that was cleared almost entirely by 1 year after exposure. Because these changes are similar to those reported in humans with chronic beryllium disease, these data suggest that the beagle represents a good model to study histologic and immunologic aspects of this disease syndrome.

Aerosols↗

PubMed1989

Characterization of the aluminum and beryllium fluoride species bound to F-actin and microtubules at the site of the gamma-phosphate of the nucleotide.

Aluminum fluoride and beryllium fluoride complexes have previously been shown to bind tightly to F-ADP-actin and GDP-microtubules in competition with Pi and to mimic the XDP-Pi transient state of the polymerization. The structure of the bound complexes is investigated here in further detail. Using a fluoride ion-specific electrode, the number of fluoride atoms per aluminum or beryllium atom in the bound complex could be determined. The results indicate that AIF-4 and either BeF2(OH)-.H2O or BeF3-.H2O are the tightly bound species in both F-actin and microtubules. The dependences of the binding on pF and pH are consistent with this conclusion. The possible geometries of aluminum and beryllium fluorides in the gamma-phosphate subsite of the nucleotide are discussed in correlation with the catalytic mechanism of nucleotide hydrolysis.

Actins↗

PubMed1986

Beryllium toxicity to human, monkey and dog cells in culture.

The toxicity of beryllium was evaluated using a mammalian cell culture system. As the ID50 (a fifty per cent inhibitory dose, to growth of cells after 72 h of incubation) values for HEL-R66, KB, Vero and MDCK cells to beryllium were 0.8 X 10(-3) mM, 1 X 10(-3) mM, 0.9 X 10(-3) mM and 1.2 X 10(-3) mM, respectively, there was no remarkable difference in the sensitivity for these cells to beryllium.

Animals↗

PubMed1985

Beryllium: laboratory evidence.

Beryllium-containing compounds have been studied extensively and have been known to be carcinogenic in animals since 1946. Beryllium salts and alloys were among the first nonradioactive, inorganic substances shown to induce osteogenic sarcoma in experimental animals. Beryllium-containing compounds have been demonstrated to be powerful pulmonary carcinogens in rats. To date, these compounds do not appear to be mutagenic, leaving open the question of their mechanism of action.

Animals↗

PubMed1982

Selective effect of the metallocarcinogen beryllium on hormonal regulation of gene expression in cultured cells.

Effects of the metallocarcinogen beryllium on regulation of gene expression were assessed by analysis of hormonal regulation of synthesis of tyrosine aminotransferase in beryllium-treated hepatoma cell cultures. Cell growth was not affected by exposure of the cells to 1 micro M BeSO4 throughout their 4- to 5-day growth cycle. In cells pretreated in this way, the induction by glucocorticoids was specifically impaired, the extent of induced enzyme synthesis being reduced about 50%. Inductions by insulin or cyclic adenosine 3':5'-monophosphate were not influenced by the metal. The results suggest that low concentrations of beryllium selectively interfere with regulatory mechanisms controlling transcriptional events in gene expression.

Animals↗

PubMed1978

[Examination of the respiratory tract in workers occupationally exposed to beryllium].

Owing to the fact that in our home literature there are no data concerning evaluation of respiratory tract status in persons occupationally exposed to beryllium, a population of one plant, exposed to beryllium in concentrations less than the MAC was subject to x-ray of chest, extended functional tests of lungs and examinations of blood gases. In the group under study, one found in 13% deviation in lungs' x-ray with limited intraparenchymatous changes, and in 46% a decrease in lungs' ventilating reservers of a small degree. Association of radiological changes with imperfection of lungs' ventilating reserve of restrictive type was found in one man who was removed from the work in exposure to beryllium, as a person with an increased risk of falling ill.

Adult↗

PubMed1993

Formation of a stable inactive complex of the sarcoplasmic reticulum calcium ATPase with magnesium, beryllium, and fluoride.

Incubation of leaky or nonionic detergent-solubilized sarcoplasmic reticulum vesicles in solutions containing magnesium, beryllium, and fluoride caused a time-dependent complete inhibition of calcium ATPase activity. The inhibited state persisted through dialysis for 2 days versus EGTA and was reversed within minutes by the presence of 0.5 mM calcium. Calcium-independent ATPase activity was unaffected. Omission of magnesium or fluoride resulted in retention of activity, while omission of beryllium produced slower inactivation, as described previously (Murphy, A. J., and Coll, R. J. (1992) J. Biol. Chem. 267, 5229-5235). Incubation of nonleaky vesicles had a similar effect, although it occurred more than 10-fold more slowly, suggesting that a component, probably beryllium, must enter the vesicles for inhibition to occur. By contrast, inhibition of nonleaky vesicles by magnesium and fluoride developed less than 2-fold more slowly. Including calcium in the incubation mixtures resulted in partial protection, so that the time course of CaATPase activity leveled off at nonzero values (for example, at 0.1 mM calcium, the activity leveled off at 43% of control). This result is most simply accounted for by a model involving simultaneous binding of calcium and a form of fluoroberyllium to the CaATPase (e.g. Ca2EMgBeFn).

Adenosine Diphosphate↗

PubMed1997

Serum neopterin in chronic beryllium disease.

We evaluated serum neopterin as a biomarker of chronic beryllium disease (CBD), for use in conjunction with the beryllium lymphocyte proliferation test (BeLPT) in workplace screening. Serum neopterin levels were determined by radioimmunoassay, and we compared levels in three groups: CBD (n = 86), beryllium sensitized (BeS) (n = 22), and normal (Nor) (n = 20). Those in the diseased group underwent pulmonary function tests, bronchoalveolar lavage (BAL), and maximal exercise testing. We correlated neopterin levels with results of these clinical parameters of disease severity. To evaluate the optimum sensitivity, specificity, and neopterin cut-off value, receiver operator characteristic (ROC) curves were generated. The median serum neopterin level in CBD was significantly higher than in BeS or in Nor [median 1.45, 25th, 75th percentiles (1.00, 2.7) ng/ml, 0.82 (0.67, 1.16) ng/ml, and 0.92 (0.86, 1.16) ng/ml, respectively] (P < 0.05). In CBD, we observed statistically significant associations between neopterin and measures of gas exchange and BAL cellularity. Using a neopterin value of 1.27 ng/ml, test specificity is 88%. In those workers with an abnormal BeLPT, serum neopterin has high positive predictive value (92%), and can identify disease, helping to distinguish it from BeS without the risks of biopsy.

Adult↗

PubMed2002

Racial differences in prevalence of a supratypic HLA-genetic marker immaterial to pre-employment testing for susceptibility to chronic beryllium disease.

BACKGROUND: A beryllium materials manufacturer is conducting a limited pilot program that offers testing for HLA-DP beta 1E69 with genetic counseling through a third party to applicants for employment. An important consideration in this regard is the prevalence of this marker in the general population, and its consequent positive predictive value of disease susceptibility. METHODS: Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine HLA-DP beta 1E69 population frequencies. Estimation of positive predictive values assumed a disease frequency among beryllium workers of either 5 or 15% and used an odds ratio for disease risk of 35 for the HLA-DP beta 1E69 marker. RESULTS: Allelic/carrier frequencies were found to be 0.21/0.33, 0.24/0.40, 0.27/0.47, and 0.38/0.59 for Caucasians, African-Americans, Hispanics, and Chinese, respectively. Ranges of positive predictive values for a genetic test based on HLA-DP beta 1E69 in these populations were calculated to be 8.3-14.3% for carriers with an assumed disease frequency of 5%. For high risk subgroups with disease frequencies of 15%, the range of positive predictive values was found to span between 24.9-43.0%. CONCLUSIONS: These estimates suggest that using HLA-DP beta 1E69 genotyping for general pre-employment screening in the beryllium industry has a low positive predictive value, which varies little among racial groups where carrier frequencies differ significantly.

Berylliosis↗

PubMed1994

Role of Liv-52 in protection against beryllium intoxication.

An ayurvedic medicine, Liv-52, was studied as a prophylactic agent against beryllium-induced toxicity in rats. Administration of beryllium per se caused severe degenerative and necrotic changes in kidneys, liver, and uterus. Beryllium exposure also reduced glycogen content, activities of alkaline phosphatase, succinate-dehydrogenase, and adenosine-triphosphatase in these organs. On the contrary, activities of acid phosphatase and glucose-6-phosphatase showed marginal increase. Liv-52-primed rats exhibited comparatively less marked toxic effects.

Animals↗