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1996 Beryllium Related Journal Articles
  1. (1996). “Radiosensitivity variations in human tumor cell lines exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays.” Strahlenther Onkol172(10): 567-72. BACKGROUND: Neutron therapy should be beneficial to patients with tumor types which are resistant to photons but relatively sensitive to high-LET radiation. In this work the potential therapeutic gain of a clinical neutron beam is evaluated by quantifying the variations in radiosensitivity of different cell lines to neutrons and photons. MATERIAL AND METHODS: Different cell lines were exposed in vitro to p(66)/Be neutrons or 60Co gamma-rays. Micronuclei frequencies in binucleated cells and surviving fractions were determined for each cell type. RESULTS: Following exposure to either 1 or 1.5 Gy neutrons, micronuclei frequencies were significantly correlated with that observed for 2 Gy photons. A weak but significant correlation between the variation in neutron RBE values, determined from survival curve inactivation parameters and the mean inactivation doses for photon exposures, was also established. CONCLUSION: It is concluded that although neutron and photon sensitivities are related, the use of this high energy neutron source may constitute a potential therapeutic gain for tumor types that can be identified as very resistant to photons. Considering that a definitive oxygen gain factor has been established for this neutron beam the observed therapeutic gain is expected to be further enhanced in tumors where hypoxia protects cells from conventional radiation damage.

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  2. Adachi, S. and K. Takemoto (1996). “Sensitometric response of the Sens-A-Ray, a charge-coupled imaging device, to changes in beam energy.” Dentomaxillofac Radiol 25(1): 17-8. OBJECTIVES: To evaluate image density (pixel values) and image contrast due to variations in beam energy (kVp) for the Sens-A-Ray intra-oral radiographic sensor. METHOD: Images of an aluminium step wedge were made at 50, 70 and 90 kVp. Mean pixel values (with standard deviations) for representative attenuator thicknesses were measured using region-of-interest histogram analysis. Corresponding entrance doses were measured using a beryllium-windowed ionization chamber. RESULTS: The steepest response slopes were found with the lowest kVp settings; hence the CCD results mimic the behaviour of standard radiographic film, with the high contrast being found with low kVp. The entrance dose resulting in pixel saturation was less with low kVp than high kVp. It is suggested that this is due to the CCD receptor being most sensitive to X-ray photons of relatively low keV. CONCLUSION: While the kVp needs to be selected in relation to both tissue and receptor characteristics, it is possible to use low kVp techniques with the Sens-A-Ray without increasing the entrance dosage.

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  3. Albright, J. F. and R. A. Goldstein (1996). “Mortality of workers at a nuclear materials production plant at Oak Ridge, Tennessee, 1947-1990 [see comments].” Am J Ind Med 29(2): 131-41. The Y-12 plant at Oak Ridge, Tennessee, produced nuclear materials for the U.S. government's nuclear weapons program beginning in 1943. Workers at Y-12 were exposed to low dose, internal, alpha radiation and external, penetrating radiation, as well as to beryllium, mercury, solvents, and other industrial agents. This paper presents updated results from a long-term mortality study of workers at Y-12 between 1947 and 1974, with follow-up of white men through 1990 and data reported for the first time for women and men of other races. Vital status was determined through searches of the National Death Index and other records, and the workers' mortality was compared to the national population's using standardized mortality ratios (SMRs) . Total mortality was low for all Y-12 workers and total cancer mortality was as expected. Among the 6,591 white men, there were 20% more lung cancer deaths than expected (95% confidence interval [CI] 1.04-1.38). Death rates from brain cancer and several lymphopoietic system cancers were also elevated among white men, with SMRs of 1.28 and 1. 46. Mortality from cancer of the pancreas, prostate, and kidney was similarly elevated. There was evidence of excess breast cancer among the 1,073 female workers (SMR 1.21, 95% CI 0.60-2.17). Lung cancer mortality among these workers warrants continued surveillance because of the link between internal alpha radiation exposure and this disease, but other agents, notably beryllium, also merit considerations as potential causes of lung cancer. Other cancers and agents should also be investigated as part of a comprehensive study of the health consequences of the production of nuclear weapons.

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  4. Allen, P. G., L. E. Laham, et al. (1996). “Tumor necrosis factor alpha gene expression in human monocytic THP-1 cells exposed to beryllium.” Arch Environ Health 51(1): 29-33. Chronic beryllium disease, which results from occupational exposure to particulate beryllium, is characterized by the development of lung granulomas and progressive pulmonary fibrosis. Increased production of proinflammatory cytokines (e.g., tumor necrosis factor alpha and interleukin-1 beta) by pulmonary alveolar macrophages occurs in many chronic fibrotic lung diseases and is thought to contribute to the disease process. The purpose of the present study was to investigate cytokine production by human monocytic cells exposed to beryllium in vitro. The results indicated that such cells respond to beryllium ions in the presence of fluoride by accumulation of messenger ribonucleic acid for both tumor necrosis factor alpha and interleukin-1 beta. These findings suggest that inhaled beryllium may directly stimulate the production of these cytokines by alveolar macrophages in vitro.

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  5. Apotheker, H., I. Nishimura, et al. (1996). “Impact of aluminium, fluoride and fluoroaluminate complex on ATPase activity of Nostoc linckia and Chlorella vulgaris.” Biometals 9(3): 277-83. This study demonstrates a pH-dependent inhibition of Mg( 2+)- and Ca(2+)-ATPase activities of Nostoc linckia and Chlorella vulgaris exposed to AlCl3, AlF3, NaF and AlCl3+ NaF together. AlF3 and the combination of AlCl3+NaF were more inhibitory to both the enzymes as compared with AlCl3 and NaF. Toxicity of the test compounds increased with increasing acidity. Interaction of AlCl3+NaF was additive on N. linckia and C. vulgaris, respectively, at pH 7.5 and 6.8, and synergistic at pH 6.0 and 4.5. In the presence of 60 and 100 microM PO4(3-) an increased NaF concentration (in the AlCl3+NaF combination) was required to produce the same degree of inhibition in ATP synthesis and ATPase activity. Toxicity of fluoroaluminate was reduced in the presence of EDTA and citrate. Except for beryllium to some extent, combinations of cadmium, cobalt, iron, manganese, tin and zinc with fluoride were not as effective as aluminium in inhibiting the ATPase activity. The presence of a 100 kDa protein band in SDS-PAGE of both control as well as AlCl3+NaF-treated samples suggested that AlF4- inhibits the ATPase activity by acting as a functional barrier without affecting the structure of the enzyme.

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  6. Bale, A. (1996). “Equilibrium studies of kinesin-nucleotide intermediates.” J Biol Chem 271(16): 9473-82. We have examined the energetics of the interactions of two kinesin constructs with nucleotide and microtubules to develop a structural model of kinesin-dependent motility. Dimerization of the constructs was found to reduce the maximum rate of the microtubule-activated kinesin ATPase 5-fold. Beryllium fluoride and aluminum fluoride also reduce this rate, and they increase the affinity of kinesin for microtubules. By contrast, inorganic phosphate reduces the affinity of a dimeric kinesin construct for microtubules. These findings are consistent with a model in which the kinesin head can assume one of two conformations, "strong" or "weak" binding, determined by the nature of the nucleotide that occupies the active site. Data for dimeric kinesin are consistent with a model in which kinesin.ATP binds to the microtubule in a strong state with positive cooperativity; hydrolysis of ATP to ADP+P(i) leads to dissociation of one of the attached heads and converts the second, attached head to a weak state; and dissociation of phosphate allows the second head to reattach. These results also argue that a large free energy change is associated with formation of kinesin.ADP.P(i) and that this step is the major pathway for dissociation of kinesin from the microtubule.

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  7. Berry, J. P., F. Escaig, et al. (1996). “Machining risk of beryllium disease and sensitization with median exposures below 2 micrograms/m3.” Am J Ind Med 30(1): 16-25. We examined the prevalence of beryllium sensitization in relation to work process and beryllium exposure measurements in a beryllia ceramics plant that had operated since 1980. We interviewed 136 employees (97.8% of the workforce), ascertained beryllium sensitization with the beryllium lymphocyte proliferation blood test, and reviewed historical industrial hygiene measurements. Of eight beryllium-sensitized employees (5.9%), six (4.4% of participating employees) had granulomatous disease on transbronchial lung biopsy. Machinists had a sensitization rate of 14.3% compared to a rate of 1.2% among other employees. Machining had significantly higher general area and breathing zone measurements than did other processes in the time period in which most beryllium- sensitized cases had started machining work. Daily weighted average (DWA) estimates of exposure for matching processes also exceeded estimates for other work processes in that time period, with a median DWA of 0.9 microgram/m3. Machining process DWAs accounted for the majority of DWAs exceeding the 2.0 micrograms/m3 OSHA standard, with 8.1% of machining DWAs above the standard. We conclude that lowering machining process-related exposures may be important to lowering risk of beryllium disease.

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  8. Biddinger, G. R. and S. P. Gloss (1996). “Binding of phosphate, aluminum fluoride, or beryllium fluoride to F-actin inhibits severing by gelsolin.” J Biol Chem 271(9): 4665-70. Actin exhibits ATPase activity of unknown function that increases when monomers polymerize into filaments. Differences in the kinetics of ATP hydrolysis and the release of the hydrolysis products ADP and inorganic phosphate suggest that phosphate-rich domains exist in newly polymerized filaments. We examined whether the enrichment of phosphate on filamentous ADP-actin might modulate the severing activity of gelsolin, a protein previously shown to bind differently to ATP and ADP actin monomers. Binding of phosphate, or the phosphate analogs aluminum fluoride and beryllium fluoride, to actin filaments reduces their susceptibility to severing by gelsolin. The concentration and pH dependence of inhibition suggest that HPO4(2-) binding to actin filaments generates this resistant state. We also provide evidence for two different binding sites for beryllium fluoride on actin. Actin has been postulated to contain two Pi binding sites. Our data suggest that they are sequentially occupied following ATP hydrolysis by HPO4(2-) which is subsequently titrated to H2PO4-. We speculate that beryllium fluoride and aluminum fluoride bind to the HPO4(2-) binding site. The cellular consequences of this model of phosphate release are discussed.

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  9. Boulahdour, H. and J. P. Berry (1996). “Intranuclear dense bodies after metal intoxication: a review of ultrastructural and microanalytical findings.” Cell Mol Biol (Noisy-le-grand) 42(3): 421-9. Abnormal intranuclear dense bodies are observed in several varieties of cells after intoxication by four varieties of metals: lead, bismuth, beryllium and neptumium. These inclusions have been studied by two microanalytical methods: Electron probe X-ray microanalysis (EPMA) and ion microscopy. A strong similarity has been observed in the ultrastructure of the dense bodies produced several weeks after beryllium and neptunium intoxication although there exists an important discrepancy between both elements concerning their physical, chemical and physico-chemical characteristics. Furthermore, these dense bodies are observed in the same varieties of cells (tubular proximal cells of kidneys, hepatocytes, pneumocytes). Intranuclear dense bodies produced by lead are also observed in the same types of cells, where they showed similar ultrastructure patterns as beryllium and neptunium inclusions but only after a long period, several years, after a chronic intoxication. The ultrastructure of the dense bodies produced by bismuth are clearly distinct from beryllium, neptunium or lead inclusions. Beryllium, neptunium and lead have been detected by EPMA or ion microscopy in the corresponding dense bodies although the real presence of bismuth remains to be confirmed in the nuclear dense bodies produced by this element.

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  10. Castle, A. G., A. Ling, et al. (1996). “Immunology, genetics, and epidemiology of beryllium disease.” Chest 109(3 Suppl): 40S-43S.

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  11. Clary, J. J., L. S. Bland, et al. (1996). “Phosphate analogs block adaptation in hair cells by inhibiting adaptation-motor force production.” Neuron17(3): 523-33. To ensure optimal sensitivity for mechanoelectrical transduction, hair cells adapt to prolonged stimuli using active motors. Adaptation motors are thought to employ myosin molecules as their force-producing components. We find that beryllium fluoride, vanadate, and sulfate, phosphate analogs that inhibit the ATPase activity of myosin, inhibit adaptation by abolishing motor force production. Phosphate analogs interact with a 120-kDa bundle protein, most likely myosin 1 beta, in a manner that coincides with their effects on adaptation. Features of transduction following inhibition of motor force production suggest that the gating and extent springs of the hair cell orient in parallel at rest and that the negative limit of adaptation arises when force in the stretched extent spring matches the force output of the adaptation motor.

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  12. Denis, J. M., J. P. Meulders, et al. (1996). “Modulation of alpha 4 beta 1 and alpha 5 beta 1 integrin expression: heterogeneous effects of Q-switched ruby, Nd: YAG, and alexandrite lasers on melanoma cells in vitro.” Lasers Surg Med 18(1): 63-71. BACKGROUND and OBJECTIVE: Integrins of the beta 1 family are cellular adhesion molecules that play an important role in cell attachment and migration by interacting with extracellular matrix molecules. Agents such as hormones, cytokines, and ultraviolet radiation have all been shown to have an integrin modulating potential. The present study indicates that radiation of Q-switched lasers is also able to induce transient changes in integrin expression levels on human melanoma cells in vitro. STUDY DESIGN/MATERIALS and METHODS: Radiation from Q-switched Ruby (694 nm), Alexandrite (755 nm), and Nd:YAG laser (1,064 nm) with fluences comparable to those that are generally used in treating dermatologic lesions were used to irradiate a subconfluent layer of human melanoma cells. After fixed time intervals, the cells were harvested either to analyse the integrin expression by flow cytometry or to investigate changes in cell attachment, spreading, and migration. RESULTS: It was established that all three types of laser were able to cause a significant downregulation of both the alpha 4 and the common beta 1 integrin subunit. The Alexandrite and Ruby lasers also induced a decrease in alpha 5 expression; however, the cells treated with the Nd:YAG laser showed a marked upregulation of the alpha 5 subunit. The expression of the other beta 1 integrin subunits was shown to be unaltered after laser treatment. Downregulation of the alpha 4 upregulation of the alpha 5 integrin subunit expression resulted in, respectively, decreased and increased attachment and spreading on fibronectin, the extracellular matrix ligand for both the alpha 4 beta 1 and alpha 5 beta 1 integrins. Marked upregulation of the alpha 5 subunit also resulted in a higher migration rate. CONCLUSION: Taken together, these results show that nonlethal doses of Q-switched laser radiation are able to induce changes in cellular behavior in vitro by modulating the integrin expression pattern.

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  13. Epstein, W. L. and V. S. Byers (1996). “Castability, opaque masking, and porcelain bonding of 17 porcelain-fused-to-metal alloys.” J Prosthet Dent 75(4): 367-74. Seventeen porcelain-fused-to-metal alloys, which represented a cross section of the various alloy types available, were evaluated for castability, opaque masking, and porcelain bond strength. The base metal alloys generally cast more completely than the noble alloys, with the presence of beryllium as an important factor for greater castability among the base metal alloys. Statistically significant differences were observed in the ability of an opaque porcelain to mask the different alloy substrates but no systematic effect of alloy type was observed. Porcelain bond testing revealed that nickel-chromium-beryllium alloys produced significantly better porcelain-metal bonds than nickel- chromium alloys without beryllium. In addition, it was found that palladium-copper alloys produced significantly better bonds with porcelain than palladium-cobalt alloys.

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  14. Finch, G. L., M. D. Hoover, et al. (1996). “Epidemiology and the identification of metals as human carcinogens.” Sci Prog 79(Pt 4): 311-26. Classification of substances as probable human carcinogens under the current IARC classification scheme is dependent on epidemiological evidence. The epidemiological data relating to the four metals currently identified as probable human carcinogens, in the metallic form or in the compounds, are reviewed and the weaknesses identified. These weaknesses lie mainly in exposure assessment. The weaknesses may be overcome to some extent by the use of metademographic methods as applied recently to the respiratory cancers that occurred at the Clydach Nickel Refinery in the first 30 years of this century. The general conclusion is that the epidemiological data relating to metals are unsatisfactory bases for the IARC classifications. There is a need to revise these classifications and to make them more precise by identifying exactly the substances which have caused human cancers.

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  15. Frome, E. L., M. H. Smith, et al. (1996). “Statistical methods for the blood beryllium lymphocyte proliferation test.” Environ Health Perspect104 Suppl 5: 957-68. The blood beryllium lymphocyte proliferation test (BeLPT) is a modification of the standard lymphocyte proliferation test that is used to identify persons who may have chronic beryllium disease. A major problem in the interpretation of BeLPT test results is outlying data values among the replicate well counts (approximately 7%). A long-linear regression model is used to describe the expected well counts for each set of Be exposure conditions, and the variance of the well counts is proportional to the square of the expected count. Two outlier-resistant regression methods are used to estimate stimulation indices (SIs) and the coefficient of variation. The first approach uses least absolute values (LAV) on the log of the well counts as a method for estimation; the second approach uses a resistant regression version of maximum quasi-likelihood estimation. A major advantage of these resistant methods is that they make it unnecessary to identify and delete outliers. These two new methods for the statistical analysis of the BeLPT data and the current outlier rejection method are applied to 173 BeLPT assays. We strongly recommend the LAV method for routine analysis of the BeLPT. Outliers are important when trying to identify individuals with beryllium hypersensitivity, since these individuals typically have large positive SI values. A new method for identifying large Sls using combined data from the nonexposed group and the beryllium workers is proposed. The log(SI)s are described with a Gaussian distribution with location and scale parameters estimated using resistant methods. This approach is applied to the test data and results are compared with those obtained from the current method.

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  16. Golitsina, N. L., A. A. Bobkov, et al. (1996). “Screening for chronic beryllium disease using beryllium specific lymphocyte proliferation testing.” Int Arch Occup Environ Health 68(6): 405-7.

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  17. Hall, E. J., M. Zaider, et al. (1996). “Dependence of mutation induction on fast-neutron energy in a human epithelial teratocarcinoma cell line (P3).” Radiat Res 145(3): 331-6. To date, few studies have evaluated the magnitude of the risks of somatic effects in humans from low-dose or protracted radiation exposure to neutrons using in vitro or in vivo techniques (A. Kronenberg, Radiat. Res. 128, S87-S93, 1991) . In earlier study a strong energy dependence was shown for neutron-induced mutations at both the hprt and the tk loci in a rodent fibroblast cell line (Zhu and Hill, Radiat. Res. 139, 300-306, 1994). Using fast neutrons produced by impinging protons on a beryllium target at the UCLA/ VA cyclotron, we have been examining the energy dependence of mutation induction at the HPRT locus in a human epithelial cell line derived from solid tumor tissue. In the present study, human epithelial teratocarcinoma cells were exposed to neutron beams produced from protons with 46, 30, 20 and 14 MeV energy. We found that cytotoxicity increased by 50% as the neutron beams produced from 46 MeV to 14 MeV, confirming many earlier reports. But as with the Chinese hamster cells, the mutation frequency at the HPRT locus increased 2.5-4-fold with decreasing neutron energy. Additionally, although there was a strong energy dependence for mutation induction, we noted that the shape of the induction curves was curvilinear for the human cells compared to the linearity of the curves obtained for the Chinese hamster cells and some other non-solid tissue human cell lines. Calculations of the RBE, using gamma rays as the standard reflected these differences. The RBE for mutation at the HPRT locus was dependent not only upon energy but also on dose, giving rise to RBEs that were in some cases distinctly different from those found in the Chinese hamster cell line. In the low-dose region (doses below 75 cGy) the maximum RBE of about 5 resulted from irradiation by the lowest-energy neutron beam (14 MeV protons on beryllium).

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  18. Howard, W. B., J. C. Yanch, et al. (1996). “Effective source size, yield and beam profile from multi- layered bremsstrahlung targets.” Phys Med Biol 41(8): 1353-79. Modern conformal radiotherapy benefits from heterogeneous dose delivery using scanned narrow bremsstrahlung beams of high energy in combination with dynamic double focused multi-leaf collimation and purging magnets. When using a purging magnet to remove electrons and positrons the target space is limited and unorthodox thin multi-layered targets are needed. A computational technique has therefore been developed to determine the forward yield and the angular distributions of the bremsstrahlung beam as well as the size and location of the effective and the virtual photon point source for arbitrary multi-layer bremsstrahlung targets. The Gaussian approximation of the diffusion equation for the electrons has been used and convolved with the bremsstrahlung production process. For electrons with arbitrary emittance impinging on targets of any multi-layer and atomic number combination, the model is well applicable, at least for energies in the range 1-100 MeV. The intrinsic bremsstrahlung photon profile has been determined accurately by deconvolving the electron multiple scattering process from thin experimental beryllium target profiles. For electron pencil beams incident on a target of high density and atomic number such as tungsten, the size of the effective photon source stays at around a tenth of a millimetre. The effective photon source for low-Z materials such as Be, C and Al is located at depths from 3-7 mm in the target, decreasing with increasing atomic number. The effective photon source at off-axis positions then moves out considerably from the central axis, which should be considered when aligning collimators. For high- Z materials such as tungsten, the location of the effective photon source is at a few tenths of a millimetre deep. The virtual photon point source is located only a few tenths of a millimetre upstream of the effective photon source both for high- and low-Z materials. For 50 MeV electrons incident on multi-layered full range targets the radial energy fluence distributions will have a full width at half maximum (FWHM) of 80 to 100 mm at 1 m from the target. The best target composition made of two layers when the space is limited to 15 mm was found to be 9 mm-Be followed by 6 mm W. A thin beryllium target (approximately 3 mm) results in a high-intensity bremsstrahlung lobe with a FWHM of about 35 mm at the isocentre. Interestingly, the forward dose rate in such a beam is as high as 62% of the maximum achievable with an optimal target design, even if on average only 1 MeV is lost by the electrons.

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  19. Inoue, Y., M. Cornebise, et al. (1996). “Genetic markers in beryllium hypersensitivity.” Chest109(3 Suppl): 45S.

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  20. Inoue, Y., T. E. King, Jr., et al. (1996). “Human mast cell basic fibroblast growth factor in pulmonary fibrotic disorders.” Am J Pathol 149(6): 2037-54. Mast cells (MCs) are abundant in fibrotic tissue, although their role in fibrogenesis remains obscure. Recent studies suggest MCs may produce basic fibroblast growth factor (bFGF). To evaluate the hypothesis that MC bFGF contributes to the fibrotic response in human interstitial lung disease, we studied lung tissue, bronchoalveolar lavage fluid and serum in 1) idiopathic pulmonary fibrosis, 2) chronic beryllium disease and sarcoidosis, 3) control subjects with no disease or who were beryllium sensitized with normal lung histology. Diseased subjects underwent clinical assessments to stage disease severity. We determined that most bFGF+ cells in lung interstitium are MCs and are most abundant in idiopathic pulmonary fibrosis. Distribution of bFGF+ MCs matched that of extracellular matrix deposition and correlated with the extent of fibrosis morphometrically. Only one bFGF isoform (17.8 kd) was found in idiopathic pulmonary fibrosis and chronic beryllium disease lung tissues and interacted with heparin-like molecules in the lung. Using a human MC line, we verified that MCs express bFGF mRNA and protein that localizes to cytoplasmic granules. Clinically, bFGF concentrations in bronchoalveolar lavage fluid and serum were highest in disease states and correlated with bronchoalveolar lavage cellularity and severity of gas exchange abnormalities, supporting a role for MC bFGF in the pulmonary fibrotic response and its clinical consequence.

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  21. Ivanova, A. L. (1996). “Review of occupational lung carcinogens.” Am J Ind Med 29(5): 474-90. Lung cancer is the most common malignancy in the United States and is ranked second only to bladder cancer in the proportion of cases thought to be due to occupational exposures. We review the epidemiology of occupational lung cancer, focusing on agents identified as pulmonary carcinogens by the International Agency for Research on Cancer. We derive estimates of overall relative risks from the major studies of these lung carcinogens, and we also provide estimates of the number of exposed workers. Using our data as well as estimates from other authors, we estimate that approximately 9,000-10,000 men and 900-1,900 women develop lung cancer annually in the United States due to past exposure to occupational carcinogens. More than half of these lung cancers are due to asbestos. This estimate is likely conservative, in that we have restricted our analysis to confirmed lung carcinogens and have ignored occupations with documented excess risk but for which the specific agents are unknown. Also, our estimate of the proportion of workers exposed in the past is probably too low. Our estimate should be viewed only as broad approximation. Nevertheless, it is in line with other estimates by authors using different methods. The current number of cases estimated to be due to occupational exposure reflects past high exposures and is likely to drop in the future, unless other occupational lung carcinogens are confirmed or new carcinogens are introduced into the workplace.

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  22. Jameson, C. W. (1996). “Effect of beryllium on delta-aminolevulinic acid dehydratase and porphobilinogen deaminase in pregnant mice.” Pharmacol Toxicol 79(4): 214-6.

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  23. Joshi, J. G. and M. Clauberg (1996). “Trace elements in drinking water coolers collected from primary schools, Riyadh, Saudi Arabia.” Sci Total Environ 181(3): 215-21. A simple method for the spectrochemical analysis of water samples by inductively coupled plasma spectrometry is described. Samples from drinking water coolers in 32 schools in Riyadh were collected at a specific time during a typical school day and analyzed for aluminum (Al), beryllium (Be), cadmium (Cd), cobalt (Co), chromium (Cr), copper (Cu), iron (Fe) , manganese (Mn), molybdenum (Mo), nickel (Ni), silicon (Si), strontium (Sr), vanadium (V), and zinc (Zn) to ascertain the water quality. The analysis of drinking water showed high concentrations of metals and in some cases exceeded the guideline limits recommended by EEC and WHO.

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  24. Kang, K., S. Shima, et al. (1996). “Medical and ethical issues in genetic screening--an academic view.” Environ Health Perspect 104 Suppl 5: 987-90. This article is intended to acquaint those whose principal concerns are the health and safety of workers with genetic screening and some of the medical and ethical issues it raises. Population-based genetic screening increasingly is being considered for predicting future disease in the person being screened. A major problem in screening for alleles that contribute to the development of common, multifactorial disorders is low sensitivity and positive predictive value. In many instances, no demonstrably effective prophylaxis or treatment is available to help those with positive test results. This creates ethical problems of assuring that testing is in the person's best interest and raises in turn issues of autonomy, discrimination, and privacy. Instead of screening for genetic predispositions to harm from workplace exposures, other means of improving the health of workers may bring greater benefits to a higher proportion of workers. The current state of genetic tests for chronic beryllium disease are considered. None are suitable for screening.

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  25. Kitaichi, M. (1996). “US Food and Drug Administration survey of cadmium, lead and other elements in clams and oysters.” Food Addit Contam13(5): 553-60. In Fiscal Years 1985/1986, the US Food and Drug Administration conducted a survey of cadmium, lead and other elements in fresh clams and oysters collected from US coastal areas in use for shellfish production. Shellfish were analysed for cadmium and lead by using a dry ash-anodic stripping voltammetric method. Other elements (aluminium, arsenic, beryllium, calcium, chromium, cobalt, copper, iron, magnesium, manganese, molybdenum, nickel, phosphorus, potassium, selenium, sodium, strontium, vanadium and zinc) were determined by using inductively coupled plasma-atomic emission spectrometry, direct current plasma-atomic emission spectrometry or hydride generation atomic absorption spectrometry. A total of 75 hardshell clam, 59 softshell clam, 104 Eastern oyster and 40 Pacific oyster samples were analysed for cadmium and lead. Average levels found were 0.09, 0.05, 0.51 and 1. 1 mg/kg wet weight for cadmium and 0.24, 0.30, 0.11 and 0.06 mg/kg wet weight for lead in hardshell clams, softshell clams, Eastern oysters and Pacific oysters, respectively. The other 19 elements were determined in 10-104 samples of the four types of shellfish. These data provide baseline values for elements in clams and oysters harvested from US coastal waters.

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  26. Knishkowy, B. and E. L. Baker (1996). “[Calorimetric study of stable complexes of myosin subfragment I with adenosine diphosphate and phosphate analogs].” Biofizika41(1): 64-72.
  27. This short review is concerned with the application of the method of differential scanning calorimetry to study the conformational changes of isolated myosin head (myosin subfragment 1, S1) caused by the formation of the S1 complexes with Mg(2+)-ADP and P(i) analogues such as orthovanadate (V), aluminium fluoride (AIF4-) or beryllium fluoride ( BeFx). These changes of the whole S1 molecule are reflected in a significant increase of S1 thermal stability and in a pronounced increase of the cooperativity of the thermal denaturation. Since the complexes S1-ADP-V, S1-ADP-AIF4- and S1-ADP-BeFx are stable analogues of the S1**-ADP-P( i) transition state of the S1-catalyzed ATP hydrolysis, it is concluded that DSC studies with these complexes offer a new and promising approach to investigate the structural changes which occur in the myosin head during Mg(2+)-ATPase reaction.

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  28. Loomis, D. P. and S. H. Wolf (1996). “Measurement of the 9Be(p,n) thick target spectrum for use in accelerator-based boron neutron capture therapy.” Med Phys 23(7): 1233-5.

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  29. Marshall, A. G. and R. J. Goodkind (1996). “The multileaf collimator for fast neutron therapy at Louvain- la-Neuve.” Bull Cancer Radiother83 Suppl: 160s-9s. The multileaf collimator of the fast neutron therapy facility at Louvain-la-Neuve is described, as well as some of the physics experiments performed in order to evaluate the attenuation of neutron beams in different materials and thus optimize the composition of the collimator leaves. The multileaf collimator consists of two sets of 22 leaves each, which can be moved independently. They are made of iron and their thickness is 95 cm. Seven borated polyethylene disks are located in the distal part of the leaves in order to absorb more efficiently the low-energy component of the neutron spectrum. The width of the leaves is 1 cm at their distal part. The leaves can move 11 cm outwards and 6 cm inwards from their reference position, and field sizes up to 25.7 x 24.8 cm, as well as irregular field shapes, can be obtained. The inner part of the leaves and their two sides are always focused on the target. The complete multileaf collimator can rotate around the beam axis, from -90 degrees to +90 degrees from the reference position. The width of the penumbra (80-20% isodoses) is 0.64 cm and 1.17 cm at the depth of the maximum buildup and at 10 cm in depth respectively, for a 10 x 10 cm field size. The collimator is adequate for the energy of the p(65)+ Be neutron beam of Louvain-la-Neuve and has been adapted to the fixed vertical beam. It has been designed following the original plans of Scanditronix, adjusted and fully assembled at the workshop of the Centre de Recherches du Cyclotron (CRC). Systematic measurements were performed in order to optimize the design and the composition of the leaves. In particular the attenuations of the actual beam and of monoenergetic neutron beams were measured in different materials such as iron and polyethylene. Above (upstream) the multileaf collimator, a fixed pre-collimator (iron thickness 50 cm; section 1 x 1 m) defines a conical aperture aligned on the largest opening of the leaves. It contains the two transmission chambers and a 2 cm thick polyethylene layer used for hardening the beam.

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  30. Meggio, F., P. Agostinis, et al. (1996). “HLA-DPB polymorphisms: Glu 69 association with sarcoidosis.” Eur J Immunogenet 23(5): 353-9. Sarcoidosis is a chronic granulomatous disorder, which is characterized by the accumulation of activated CD4+ T lymphocytes (T cells) at disease sites. There is up-regulation of cell surface expression of MHC molecules in sarcoidosis, and it has been suggested that specific MHC class II alleles are associated with the disease. A study of chronic beryllium disease (CBD), a granulomatous disorder which is pathologically similar to sarcoidosis, has identified an association between this disease and the presence of a glutamine residue at position 69 (Glu 69+) of the B1 chain of the HLA-DPB molecule. A further study also suggested the importance of Glu at position 55 of the same chain. The aims of the present study were to attempt to define MHC class II alleles associated with sarcoidosis by comparison of their frequency in two groups of subjects and to compare the frequency of HLA- DPB1 Glu 69+/- and Glu 55+/-alleles in the same subjects. Forty-one subjects with sarcoidosis and 76 normal subjects were studied. The polymorphic regions of the class II MHC were identified by PCR in association with sequence-specific oligonucleotide probes. There were no significant differences in the phenotype frequencies of MHC class II or Glu 55+ alleles between the two groups of subjects. However, there was a significant increase (P = 0.02) in the frequency of HLA-DPB1* Glu 69+ alleles compared with the control population. We therefore suggest that the presence of a Glu residue at position 69 on the DPB1 chain may play an important role in antigen presentation and recognition in chronic granulomatous diseases.

    31.  
  31. Missiaen, L., F. Wuytack, et al. (1996). “Rocky Flats Beryllium Health Surveillance.” Environ Health Perspect 104 Suppl 5: 981-6. The Rocky Flats Beryllium Health Surveillance Program ( BHSP), initiated in June 1991, was designed to provide medical surveillance for current and former employees exposed to beryllium. The BHSP identifies individuals who have developed beryllium sensitivity using the beryllium lymphocyte proliferation test (BeLPT). A detailed medical evaluation to determine the prevalence of chronic beryllium disease (CBD) is offered to individuals identified as beryllium sensitized or to those who have chest X-ray changes suggestive of CBD. The BHSP has identified 27 cases of CBD and another 74 cases of beryllium sensitization out of 4268 individuals tested. The distribution of BeLPT values for normal, sensitized, and CBD-identified individuals is described. Based on the information collected during the first 3 1/3 years of the BHSP, the BeLPT is the most effective means for the early identification of beryllium-sensitized individuals and to identify individuals who may have CBD. The need for BeLPT retesting is demonstrated through the identification of beryllium sensitization in individuals who previously tested normal. Posterior/anterior chest X-rays were not effective in the identification of CBD.

    32.  
  32. Newman, L. S. (1996). “Mast cell-associated basic fibroblast growth factor in the fibrotic response to environmental toxins. The Beryllium Model.” Chest109(3 Suppl): 43S-44S.

    33.  
  33. Newman, L. S. (1996). “Animal models of beryllium-induced lung disease.” Environ Health Perspect 104 Suppl 5: 973-9. The inhalation Toxicology Research Institute (ITRI) is conducting research to improve the understanding of chronic beryllium disease (CBD) and beryllium-induced lung cancer. Initial animal studies examined beagle dogs that inhaled BeO calcined at either 500 or 1000 degrees C. At similar lung burdens, the 500 degrees C BeO induced more severe and extensive granulomatous pneumonia, lymphocytic infiltration into the lung, and positive Be-specific lymphocyte proliferative responses in vitro than the 1000 degrees C BeO. However, the progressive nature of human CBD was not duplicated. More recently, Strains A/J and C3H/Hej mice were exposed to Be metal by inhalation. This produced a marked granulomatous pneumonia, diffuse infiltrates, and multifocal aggregates of interstitial lymphocytes with a pronounced T helper component and pulmonary in situ lymphocyte proliferation. With respect to lung cancer, at a mean lung burden as low as 17 micrograms Be/g lung, inhaled Be metal induced benign and/or malignant lung tumors in over 50% of male and female F344 rats surviving > or = 1 year on study. Substantial tumor multiplicity was found, but K-ras and p53 gene mutations were virtually absent. In mice, however, a lung burden of approximately 60 micrograms (-300 micrograms Be/g lung) caused only a slight increase in crude lung tumor incidence and multiplicity over controls in strain A/J mice and no elevated incidence in strain C3H mice. Taken together, this research program constitutes a coordinated effort to understand beryllium-induced lung disease in experimental animal models.

    34.  
  34. Newman, L. S., J. Lloyd, et al. (1996). “Significance of the blood beryllium lymphocyte proliferation test.” Environ Health Perspect 104 Suppl 5: 953-6. The blood beryllium lymphocyte proliferation test (BeLPT) is an in vitro measure of the beryllium antigen-specific cell-mediated immune response. This response to beryllium is now understood to play a central role in the immunopathogenesis of chronic beryllium disease (CBD). Although there remain some unresolved methodologic issues with testing, the blood BeLPT has already undergone sufficient development and field assessment to lead to a number of important conclusions: a) The BeLPT identifies beryllium sensitization and CBD earlier and better than any other clinical test presently available. b) The CBD cases identified with the blood test are clinically significant. c) A subset of the people identified by the BeLPT who do not yet have clinical disease will progress and require treatment with corticosteroids for impairing illness. d) The BeLPT can be used to improve clinical diagnostic accuracy and to correct mistaken diagnoses. e) The blood test can be used in screening large numbers of exposed workers because it is sensitive and specific and has high positive and negative predictive value for CBD. f) In every workforce studied to date, the BeLPT has identified beryllium sensitization and CBD that had been missed by conventional screening efforts. g) Worker populations that have been characterized using the BeLPT can help to elucidate the role of exposure genetics and dysregulated inflammation in the genesis of occupational lung disease.

    35.  
  35. Pritchard, D. J., M. P. Finkel, et al. (1996). “Airborne pollutants and the immune system.” Otolaryngol Head Neck Surg 114(2): 232-8. The effects of airborne pollutants on the immune system have been most widely studied in the respiratory tract. Entry may occur as a volatile gas (ozone, benzene), as liquid droplets (sulfuric acid, nitrogen dioxide), or as particulate matter (diesel exhaust, aromatic hydrocarbons) . The subsequent interaction with the immune system may result in local and systemic responses, and studies have shown examples of disease occurring from both overactive immune responses and immunosuppression. For the most part, airborne pollutants (small molecular weight chemicals) have to be coupled with other substances (proteins or conjugates) before they can be recognized by the immune system and exert their effects. Fortunately, this encounter rarely causes immunologically mediated human disorders. The following briefly reviews some of the disorders that may occur. Immunologically nonspecific inflammation of the lung can occur after inhalation of ozone in anyone given sufficient dose and time of exposure. Immunologically specific cell-mediated (T lymphocyte) reactions appear to predominate in chronic beryllium disease, which results in a granulomatous form of lung disease. Beryllium alone does not appear to be antigenic but requires chemical linkage with a larger molecule. Mercury-induced autoimmune disease (immune system attacks self-antigens) affecting kidneys and lungs has been demonstrated in animal models (changes similar to those seen in people with Goodpasture' s syndrome). Immunosuppression can be demonstrated after exposure to polycyclic aromatic hydrocarbons (2,3,7,8-tetrachlorodibenzo- p-dioxin). Hypersensitivity (or allergic) reactions can occur after exposure to toluene diisocyanate (occupational asthma). In summary, airborne pollutants may cause a wide spectrum of immunologically mediated disorders. There is clearly an underlying genetic basis for the susceptibility to immunologic disease resulting from exposure to pollutants, but knowledge in this area is rudimentary at present. Studies have been impeded by lack of appropriate in vitro models, as well as difficulties in identifying the biologically active substance.

    36.  
  36. Robinson, J. D., R. L. Davis, et al. (1996). “Patch testing with beryllium alloy samples in guinea pigs.” Contact Dermatitis 34(3): 196-200. An experimental study was conducted in guinea pigs for the predictive assessment of the beryllium alloy hazard in occupational exposure of the skin to beryllium compounds. Guinea pigs were sensitized to beryllium sulfate according to the maximized Magnusson and Kligman test, and challenged with beryllium alloys and metallic copper, beryllium and aluminum samples. Results showed a delayed skin hypersensitivity reaction in 30 to 60% of pre-sensitized guinea pigs challenged with copper-beryllium alloys and aluminum-beryllium alloy. An inflammatory follicular reaction was induced by copper in both controls and pre-sensitized guinea pigs.

    37.  
  37. Rossman, M. D. (1996). “Chronic beryllium disease: diagnosis and management.” Environ Health Perspect 104 Suppl 5: 945-7. Chronic beryllium disease is predominantly a pulmonary granulomatosis that was originally described in 1946. Symptoms usually include dyspnea and cough. Fever, anorexia, and weight loss are common. Skin lesions are the most common extrathoracic manifestation. Granulomatous hepatitis, hypercalcemia, and kidney stones can also occur. Radiographic and physiologic abnormalities are similar to those in sarcoidosis. While traditionally the pathologic changes included granulomas and cellular interstitial changes, the hallmark of the disease today is the well-formed granuloma. Immunologic studies have demonstrated a cell-mediated response to beryllium that is due to an accumulation of CD4+ T cells at the site of disease activity. Diagnosis depends on the demonstration of pathologic changes (i.e., granuloma) and evidence that the granuloma was caused by a hypersensitivity to beryllium (i.e., positive lung proliferative response to beryllium) . Using these criteria, the diagnosis of chronic beryllium disease can now be made before the onset of clinical symptoms. Whether, with early diagnosis, the natural course of this condition will be the same as when it was traditionally diagnosed is not known. Currently, corticosteroids are used to treat patients with significant symptoms or evidence of progressive disease.

    38.  
  38. Sakaguchi, S., T. Sakaguchi, et al. (1996). “Conference on beryllium-related diseases. Research Triangle Park, North Carolina, November 8-10, 1994. Proceedings.” Environ Health Perspect 104 Suppl 5: 933-98.

    39.  
  39. Sakaguchi, T., S. Sakaguchi, et al. (1996). “[The changes of complement activities in sera of mice after subcutaneous administration of beryllium chloride].” Nippon Eiseigaku Zasshi 50(6): 1077-83. We studied changes of the complement pathway activities and the content of C3 in sera of mice, administered BeCl2 (containing 5 micrograms of Be per mouse) or CuCl2 (containing 5 micrograms of Cu per mouse) by a single subcutaneous injection. The value of the classical complement pathway activity (CH50) of the Be group 3 days after administration was significantly higher than that of the control group (P < 0.001). It was significantly lower than in the control group after 7 days (P < 0.001). On the other hand, the CH50 value of the Cu group 3 hr after administration tended to increase, however, it was significantly lower than in the control group after 7 days (P < 0.01). The change of the alternative complement pathway activity (ACH50) value of the Be group was similar to the change of the CH50 value of the group. The ACH50 value of the Cu group 3 days after administration tended to increase but it was the same as the ACH50 value of the control group after 7 days. The C3 contents of both the Be and Cu groups 3 days after administration were significantly higher than in the control group (P < 0.001). The aspartate aminotransferase (AST) activity of the Be group 7 days after administration was significantly higher than that of the control group (P < 0.01). By contrast, AST activity of the Cu group 3 hr after administration was significantly higher than in the control group (P < 0.05). The value of the alanine aminotransferase (ALT) activity of the Be group was low (P < 0.01), but that of the Cu group was high (P < 0.05), 3 hr after administration. These values of both groups after 7 days, however, were significantly higher than in the control group (P < 0.05) . The AST/ALT ratio in mice was very high at 3 hr, and it remained high by 7 days after Be injection. On the other hand, the ratio of the Cu group was almost constant for 7 days after Cu injection. Thus, these values changed with relative expedition after Be injection. Therefore, we confirmed that measurements of complement activities and the content of C3 were valuable indices for assaying acute effects of Be on mice.

    40.  
  40. Sharma, S. and C. K. Hill (1996). “Introduction to the conference on beryllium-related diseases.” Environ Health Perspect 104 Suppl 5: 935-6.

    41.  
  41. Shea, K. G., G. A. Lundeen, et al. (1996). “Inability of energy dispersive X-ray analysis to identify particulate polyethylene.” J Biomed Mater Res 30(2): 175-80. There are limitations to all techniques used to identify particulate polyethylene in histological specimens. The goal of our study was to determine if remnant metal elements used during the catalytic production of ultra high molecular weight polyethylene, could be used as markers for particulate polyethylene detection in histological specimens. It was hypothesized that these catalyst elements could be detected in polyethylene using energy dispersive X-ray elemental analysis. Six samples from five different companies were evaluated. These included virgin polymer powder, polyethylene bar stock, and artificial joint components. Five specimens from each of the six samples were analyzed with energy dispersive X-ray elemental analysis. After elemental analysis was completed, only 2 of 30 specimens were positive for the catalyst elements. In the remaining 28 specimens, catalyst elements were not detected. Our investigation demonstrates that energy dispersive X-ray elemental analysis is not currently a feasible method of particulate polyethylene detection. Additional techniques will need to be developed to accurately identify particulate polyethylene in histological specimens.

    42.  
  42. Sibirnyi, A. A. and G. M. Shavlovskii (1996). “Retrospective beryllium exposure assessment at the Rocky Flats Environmental Technology Site.” Am Ind Hyg Assoc J 57(9): 804-8. The purpose of this study was to determine how two types of sampling data could be used for an exposure assessment in a beryllium shop at the Department of Energy's Rocky Flats Plant. Beryllium exposure was assessed via fixed airhead (FAH) sampling, in which the filter cassette was affixed to the machine, generally within a few feet of the worker's breathing zone. Approximately 500,000 FAH samples were collected for beryllium over three decades at the site. From 1984 to 1987, personal breathing zone (PBZ) samples also were collected as part of the evaluation of a new high velocity/lcw volume local exhaust ventilation system in the beryllium shop. FAH data indicated that four statistically different exposure periods existed from 1970 to 1988, as the FAH annual arithmetic means varied with changes in the local exhaust ventilation system and production levels. A matched comparison between the FAH and PBZ sample data found no direct linear correlation (R2 = 0.014); however, the mean PBZ results were higher than the mean FAH results (p = 0.0001). The mean PBZ level was 1.04 micrograms/m3 while the FAH average was 0.16 microgram/m3 (permissible exposure limit for beryllium: 2 micrograms/m3). A health surveillance program to identify cases of chronic beryllium disease (CBD) and beryllium sensitization has been implemented at Rocky Flats. To date, 53 cases of CBD and 86 cases of sensitivity to beryllium have been diagnosed. Continuing studies are evaluating semiquantitative dose response relationships for CBD using the exposure data discussed herein.

    43.  
  43. Slabbert, J. P., T. Theron, et al. (1996). “A variety of fast neutron beams for radiobiological research.” Bull Cancer Radiother 83 Suppl: 170s-2s. The design and construction of a new fast neutron facility and first dosimetric results obtained from seven neutron beams are presented. The neutrons are produced by bombarding beryllium targets with protons and deuterons from our K = 32 negative ion cyclotron. The dose rate in air 1 m distance from the thick target within a 13 x 13 cm2 field amounts to about 50 cGy/min at 30 microA of 32 MeV protons.

    44.  
  44. Souhrada, M. and J. F. Souhrada (1996). “Complexes of myosin subfragment-1 with adenosine diphosphate and phosphate analogs: probes of active site and protein conformation.” Biophys Chem 59(3): 341-9. Previous work has revealed phosphate-dependent differences in the complexes formed from myosin subfragment-1 with adenosine diphosphate (S1.ADP) and aluminum fluoride (AlF4- ) or beryllium fluoride (BeFx) [Phan and Reisler, Biophys. J., 66 (1994) A78], with the former resembling more the S1**.ADP.Pi state while the latter resembles more the S1. ATP state. In this work, the conformations of the S1.epsilon ADP.AlF4- and S1.epsilon ADP.BeFx, complexes were examined by nucleotide chase and collisional quenching experiments. epsilon ADP release from S1.epsilon ADP.AlF4- was slower than that from S1.epsilon ADP.BeFx. However, acrylamide titrations of S1.epsilon ADP.AlF4- and S1.epsilon ADP.BeFx showed little difference in nucleotide protection from quenching between the two complexes. This contrasts with the earlier observation on phosphate analog-dependent changes in the reactivity of the SH1 group on S1. To confirm phosphate- related perturbation of the SH1-SH2 sequence, emission spectra of fluorescein (IAF)-labeled SH1 and IANBD-labeled SH2 were recorded for S1 complexes with nucleotides and phosphate analogs. Considerable differences were found between the BeFx and AlF4- complexes with S1.MgADP for both SH1- and SH2-labeled proteins. These results are consistent with a recent crystallographic study of S1 complexes with ADP and phosphate analogs [Fisher et al., Biophys. J., 68 (1995) 19S] and the idea that the opening of the nucleotide cleft on S1 does not change much during ATP hydrolysis [Franks-Skiba et al., Biochemistry, 33 (1994) 12720], while significant changes in the SH1-SH2 region accompany phosphate cleavage.

    45.  
  45. Stubbs, J., E. Argyris, et al. (1996). “Effect of divalent cations on the formation and stability of myosin subfragment 1-ADP-phosphate analog complexes.” Biochemistry35(14): 4409-16. Myosin belongs to the family of motor proteins. Its interaction with actin coupled with hydrolysis of ATP is the molecular basis of muscle contraction. The head segment of myosin, called subfragment 1 (S1), contains the distinct binding sites for ATP and actin and responsible for the ATPase activity. The rate-limiting step of the ATP hydrolysis is the dissociation of the S1-MgADP-Pi complex which is accelerated by actin. The substitution of Pi with phosphate analogs (PA), such as vanadate (Vi) or beryllium fluoride (BeF(x)), highly stabilizes the complex. We studied the role of the divalent cations in the ATPase activity and in the formation and decomposition of PA-containing stable complexes by substituting Mg2+ with Fe2+, Mn2+, Ni2+, Co2+ , and Ca2+. These metal ions supported the actin activation of S1 ATPase and affected the obtained kinetic parameters, Km and V(max). The ATPase activity of S1 in the absence of actin increased with the increasing ionic radius of the metal (Me) ions. These ions also substituted for Mg2+ in the formation of the stable ternary S1-MeADP-PA complexes, which cannot be generated in the absence of divalent cations. Upon formation of stable ternary complexes, S1 reversibly loses its ability to catalyze the hydrolysis of ATP. The formation of the complexes can be followed by monitoring the disappearance of the ATPase activity. The rate of the complex formation depends on the divalent cation present and decreases in the order Mn > Fe > Ni > Co > Mg and Ca > Mn > Fe > Mg > Co in the Vi- and BeF(x)-containing complexes, respectively. The ATPase activity of S1 is recovered upon addition of actin, which causes the decomposition of the complex. The spontaneous decomposition of the complexes was studied in the presence of ethylenediaminetetraacetic acid (EDTA), which chelates the metal divalent cations released from the complex and prevents its reformation. The rate of decomposition was assessed by monitoring the recovery of the ATPase activity of S1 in the presence of EDTA. The rate of decomposition of the Vi- and BeF(x)-containing complexes follows the order Mn > Fe > Co > Mg > Ni and Ca >> Mn > Fe > Co > Mg, respectively. The rate of decomposition increases with the increasing ionic radius of the metal ions, similarly as observed in the case of ionic radius dependence of the ATPase activity. On the basis of this similarity, it is assumed that the decomposition of the complexes consists of two steps, the first step being the very slow release of PA followed by a rapid dissociation of MeADP from S1. The stability of the complexes has been calculated from the formation and decomposition rates. Except in the case of Mg, the stabilities of the BeF(x) complexes are higher than those containing Vi. The results indicate that the metal cations have a significant role in maintaining the proper structure of the transient state complex in the myosin-catalyzed ATP hydrolysis.

    46.  
  46. Svensson, R. and A. Brahme (1996). “A moral history of the evolution of a caste of workers.” Environ Health Perspect 104 Suppl 5: 991-8. Using a dialectic method of philosophic inquiry, the actual ethical, legal, and social situation associated with genetic testing of beryllium-exposed workers in Department of Energy nuclear weapons facilities for markers of chronic beryllium disease is described. The cultural evolution of a caste system in a similar situation, and its social and biological implications, among uranium miners in the Erz Gebirge of Central Europe and on the Colorado Plateau of the United States, marked by suicide and lung disease, including cancer, is also described. The historically persistent social disease resulting from these situations. The Masada Syndrome, named from an analogous situation in biblical times, is characterized. Cultural intervention, a necessary condition for the ethical progression of the Human Genome Project, is outlined.

    47.  
  47. Tatianenko, L. V., L. A. Gromova, et al. (1996). “Possible health risks from low level exposure to beryllium.” Toxicology 111(1-3): 213-24. The first case of chronic beryllium disease (CBD) at the Rocky Flats Environmental Technology Site (Rocky Flats) was diagnosed in a machinist in 1984. Rocky Flats, located 16 miles northwest of Denver, Colorado, is part of the United States Department of Energy (DOE) nuclear weapons complex. Research and development operations using beryllium began at Rocky Flats in 1953, and beryllium production operations began in 1957. Exposures could have occurred during foundry operations, casting, shearing, rolling, cutting, welding, machining, sanding, polishing, assembly, and chemical analysis operations. The Beryllium Health Surveillance Program (BHSP) was established in June 1991 at Rocky Flats to provide health surveillance for beryllium exposed employees using the Lymphocyte Proliferation Test (LPT) to identify sensitized individuals. Of the 29 cases of CBD and 76 cases of beryllium sensitization identified since 1991, several cases appear to have had only minimal opportunistic exposures to beryllium, since they were employed in administrative functions rather than primary beryllium operations. In conjunction with other health surveillance programs, a questionnaire and interview are administered to obtain detailed work and health histories. These histories, along with other data, are utilized to estimate the extent of an individual's exposure. Additional surveillance is in progress to attempt to characterize the possible risks from intermittent or brief exposures to beryllium in the workplace.

    48.  
  48. Tinkle, S., L. Kittle, et al. (1996). “Differential scanning calorimetric study of the complexes of modified myosin subfragment 1 with ADP and vanadate or beryllium fluoride.” J Muscle Res Cell Motil 17(4): 475-85. The effects of various modifications of rabbit skeletal myosin subfragment 1 on the thermal denaturation of subfragment 1 in ternary complexes with Mg-ADP and orthovanadate (V1) or beryllium fluoride (BeFx) have been studied by differential scanning calorimetry. It has been shown that specific modifications of SH1 group of Cys-707 by different sulfhydryl reagents, trinitrophenylation of Lys-83, and reductive methylation of lysine residues promote the decomposition of the S1. ADP.Vi complex and change the character of structural transitions of the subfragment 1 molecule induced by the formation of this complex, but they have much less or no influence on subfragment 1 thermal stability in the S1.ADP.BeFx complex. Thus, the differential scanning calorimetric studies on modified subfragment 1 preparations reveal a significant difference between S1.ADP.Vi and S1.ADP.BeFx complexes. It is suggested that S1.ADP.Vi and S1.ADP.BeFx complexes represent structural analogues of different transition states of the ATPase cycle, namely the intermediate states S1**.ADP.Pi and S1*.ATP, respectively. It is also proposed that during formation of the S1.ADP.Vi complex the region containing both Cys-707 and Lys-83 plays an important role in the spread of conformational changes from the active site of subfragment 1 ATPase throughout the structure of the entire subfragment 1 molecule. In such a case, the effects of reductive methylation of lysine residues on the subfragment 1 structure in the S1.ADP.Vi complex are related to the modification of Lys-83.

    49.  
  49. Tinkle, S. S., P. W. Schwitters, et al. (1996). “Cytokine production by bronchoalveolar lavage cells in chronic beryllium disease.” Environ Health Perspect 104 Suppl 5: 969-71. Chronic beryllium disease (CBD) begins as a sensitizing cell-mediated immune response to beryllium antigen that progresses to granulomatous lung disease. Previous studies demonstrated the involvement of proinflammatory cytokines in the disease process, but the pattern and regulation of cytokine release is unknown. Using bronchoalveolar lavage (BAL) cells from CBD patients in short-term tissue culture, we evaluated cytokine protein levels by enzyme-linked immunosorbent assay and T-lymphocyte proliferation by tritiated thymidine incorporation. We observed the beryllium-stimulated release of tumor necrosis factor-alpha (TNF-alpha), interleukin- 6 (IL-6), interleukin-2 (IL-2), and interferon-gamma (IFN- gamma) but not interleukin-4 (IL-4). Beryllium-stimulated IFN-gamma release was sustained to 168 hr in culture, whereas IL-2 concentrations returned to baseline after 24 hr. Neutralization of IL-2 decreased beryllium-stimulated T-lymphocyte proliferation, but the level of proliferation remained elevated in comparison to unstimulated BAL cells. These data suggest that T helper 1 (Th1) lymphocytes participate in the beryllium disease process; that IFN-gamma levels remain elevated after IL- 2 levels return to baseline; and that IL-2 participates directly in beryllium-stimulated T-cell proliferation, but other T-lymphocyte mitogenic cytokines may be involved.

    50.  
  50. van Leeuwen, R. L., S. K. Dekker, et al. (1996). “Role of lasertripsy in the management of ureteral calculi: experience with alexandrite laser system in 232 patients.” J Endourol 10(4): 345-8. In 232 patients with ureteral stones, lasertripsy was used as primary treatment or as second-line therapy after extracorporeal shockwave lithotripsy (SWL). In all patients, a semirigid 6.5F ureteroscope or a flexible 6F ureteroscope was used. Lithotripsy was performed employing an alexandrite laser with an energy of 50 to 65 mJ. The immediate success rate was 67.5% for stones in the upper ureter, 86.1% for those in the midureter, and 94.5% for those in the distal ureter. In 16.5% of the treatments, it was necessary to insert a double-J stent. A perforation of the ureter happened in two patients (0.9%), but no laser-related complications were seen. Stone fragmentation was not dependent on stone composition or size. Using small semirigid or flexible ureteroscopes, lasertripsy of ureteral stones is a minimally invasive treatment with an insignificant complication rate. In case of midureteral stones, our results revealed a higher immediate stone-free rate than is reported in the literature after treatment by SWL, and we can therefore recommend lasertripsy as primary treatment. For upper ureteral stones, lasertripsy can be recommended as a helpful auxillary procedure. Furthermore, in cases of distal ureteral stones, lasertripsy challenges SWL as the primary treatment.

    51.  
  51. Vynckier, S., P. Pihet, et al. (1996). “Beryllium stimulates release of T helper 1 cytokines interleukin- 2 and interferon gamma from BAL cells in chronic beryllium disease.” Chest 109(3 Suppl): 5S-6S.

    52.  
  52. Wagner, M. (1996). “The natural history of beryllium sensitization and chronic beryllium disease.” Environ Health Perspect 104 Suppl 5: 937-43. 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.

    53.  
  53. Wang, C. C. and C. S. Hsu (1996). “[The bonding mechanisms of base metals for metal-ceramic crown microstructure analysis of bonding agent and gold bond between porcelain and base metals].” Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 12(6): 326-38. The use of base metal alloys for porcelain fused to a metal crown and bridges has increased recently because of lower price, high hardness, high tensile strength and high elastic modulus. The addition of beryllium to base metal alloys increased fluidity and improved casting fitness. Beryllium also controlled surface oxidation and bonding strength. The bonding agent and gold bonding agent also affected the bonding strength between porcelain and metal alloys. Four commercially available ceramic base alloys were studied (two alloys contained beryllium element, another two did not). The purpose of this investigation was to study the microstructure between porcelain matrix, bonding agent and alloy matrix interfaces. A scanning electron micro- probe analyzer and energy dispersive X-ray spectroscopy (EDXS) were used to study the distribution of elements (Ni, Cr, Mo, Cu, O, Si, Sn, Al) in four base alloys. The following results were obtained: 1. The thickness of the oxidized layer of Rexillium III alloy and Unitbond alloy (contained beryllium) was thinner than Unibond alloy and Wiron 88 alloy (no beryllium). 2. The thickness of the oxidized layer of alloys in air (10 minutes and 30 minutes) was thinner in Unitbond (2.45 microns and 3.80 microns) and thicker in Wiron 88 (4.39 microns and 5.96 microns) . 3. The thickness of the oxidized layer occurring for a duration of ten minutes (in vaccum) showed that the Rexillium III alloy was the thinnest (1.93 microns), and Wiron 88 alloy was the thickest (2.30 microns). But in thirty minutes (vacuum), Unitbond alloy was the thinnest (3.37 microns) , and Wiron 88 alloy was the thickest (5.51 microns). 4. The intensity of Cr elements was increased obviously near the interface between Unitbond alloy, Wiron 88 alloy (no beryllium) and oxidized layer, but the intensity of Ni and Mo elements was slightly increased. The intensity of Cr element was not increased markedly between Rexillium III alloy, Unitbond alloy (beryllium) and oxidized layer. 5. A white-grayish oxidized layer appeared at the metal- ceramic interfaces but the thickness of oxidized layer was not obviously different. 6. The use of bonding agent at metal-ceramic interface leads to the deposition of many Sn elements at about 40 microns range within the porcelain surface. 7. Second interaction phases at the porcelain layer appeared when gold bonding agent was used, and a 50-100 microns microleakage occurred at the metal-ceramic interface.

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  54. Williams, W. J. (1996). “United Kingdom Beryllium Registry: mortality and autopsy study.” Environ Health Perspect 104 Suppl 5: 949-51. 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.

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  55. Wu, Y. T. and C. S. Hsu (1996). “[The shear bond strength of porcelain and base metal alloys for metal-ceramic crown the study of metal roughness and microstructure].” Kao Hsiung I Hsueh Ko Hsueh Tsa Chih 12(12): 728-36. The metal-ceramic crown has become a predominant restoration in fixed prosthodontics. The base metal has the quality of lower price, high tensile strength, high elastic modulus. The base metal alloy that contain beryllium element increases fluidity and improved casting performance. Beryllium also controls surface oxidation and affects the metal ceramic bonds. Preparation of surface prior to porcelain bonding has been a subject of controversy among dental ceramists. Two ceramic base metal alloys (one alloy contains beryllium, another is not) were studied. This investigation evaluated the polishing effects of 50 microns, 100 microns aluminum oxide sandblasting, carbide bur, carborundum point and separating disk upon two base metal alloys, Rexillium III and Wiron 88. A scanning electron microscope was used to study the surface texture. The following results were obtained: 1. The most roughest surface was created with 50 microns aluminum oxide sandblasting. The carbide bur produced the least roughed surface. 2. There are specific surface texture patterns after polishing with five different grinding materials. 3. The metal surfaces treated with 50 microns and 100 microns aluminum oxide have same micro-structure pictures, but there are much more undercuts treated with 100 microns aluminum oxide. 4. The usage of carbide bur resulted in less undercuts of metal surface at two metal alloys. 5. The usage of carborundum point and disk resulted in abrasive particles that retained on the grinding metal surface at two metal alloys. 6. The surface of Wiron 88 alloy usually had wrinkle texture but not the Rexillium III alloy.

  56. Zissu, D., S. Binet, et al. (1996). “[Differential diagnosis of berylliosis/sarcoidosis in a dental technician].” Dtsch Med Wochenschr 121(47): 1462-6. HISTORY AND CLINICAL FINDINGS: Sarcoidosis was diagnosed in a dental technician when he was aged 21 years. Two years later prednisolone treatment was started and continued for 14 years because of nonproductive cough with progressive reduction in vital capacity and CO transfer capacity. Subsequently the risk of exposure to beryllium-containing dust in dental laboratories became known. In his case exposure had started before sarcoidosis had been diagnosed and had continued for 16 years. Changes typical of sarcoidosis (unproductive cough and dyspnoea; bihilar lymphadenopathy and reticulonodular marking in the chest radiogram) were now present, at the age of 40 years. INVESTIGATIONS: Vital and diffusion capacities were diminished, serum levels of angiotensin-converting enzyme (141 U/I) and of neopterin (5.8 mg/l) were increased. Beryllium-lymphocyte transformation test of peripheral mononuclear cells after invitro culture with beryllium sulphate gave a raised stimulation index, and the intracutaneous beryllium sensitisation test was positive. This indicated sensitisation to beryllium even 9 years after exposure had ceased. CONCLUSION: Even after exposure to beryllium has ended, proof of exposure together with clinical and radiological findings typical of sarcoidosis and beryllium sensitisation can provide the diagnosis of berylliosis.
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