Development of Beryllium Lymphocyte Transformation Tests in Chronic Beryllium Disease

Wr, Williams; Wj, Williams

doi:10.1159/000233010

Cited by 35 publications

(16 citation statements)

References 3 publications

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“…In chronic berylliosis, beryllium-sensitive lymphocytes have been described for humans [6,16,29], guinea pigs [30], mice [13], and dogs [32], In our study, we observed a re duced BeS04 response when compared to controls. Howev er, in combination with incomplete Freund's adjuvant, a low, but significant anti-BeS04 response could be observed (table 1).…”

Section: Discussionsupporting

confidence: 63%

“…Indeed, a clinical differentiation of sarcoidosis from berylliosis is dif ficult because the two diseases are clinically similar and are identical concerning the cells recovered from the lung, by bronchoalveolar lavage, and the presence of noncaseating granuloma [4,5], The differential diagnosis relies primarly on the case history and on the documentation of a beryllium response of peripheral blood mononuclear cells or, better, bronchoalveolar lavage cells [13][14][15][16][17].…”

Section: Discussionmentioning

confidence: 99%

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Beryllium-Induced Disturbances of the Murine Immune System Reflect Some Phenomena Observed in Sarcoidosis

Pfeifer

Bartlett²,

Strausz

et al. 1994

Int Arch Allergy Immunol

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Sarcoidosis is a systemic granulomatous disorder of unknown origin. In respect to clinical and immunological characteristics, it is indistinguishable from berylliosis. As an approach to develop a murine model reflecting some aspects of sarcoidosis, we attempted to induce berylliosis in mice by treating inbred F1 mice (C57B16 × DBA/2) with 3 mg beryllium sulfate (BeSO₄) per kg body weight intraperitoneally. Either pure BeSO₄ or BeSO₄ in combination with incomplete Freund’s adjuvant was administered. Alternatively, pure BeSO₄ was injected 2 days after a single application of cyclophosphamide (150 mg/kg). The spleen index, the spontaneous and phorbolmyristate acetate (PMA)-induced radical oxygen intermediates (ROI) released by peritoneal macrophages, and the proliferative activity of spleen mononuclear cells in response to BeSO₄ and concanavalin A (ConA) were evaluated and compared to the corresponding changes observed in sarcoidosis. In all three modes of BeSO₄ treatment, the spontaneous ROI release by peritoneal macrophages was significantly elevated. These elevations were very similar to those observed with alveolar macrophages in active sarcoid alveolitis. After BeSO₄ treatment, a small proliferative activity of spleen mononuclear cells in response to BeSO₄ could be observed. Further, BeSO₄-treated spleen mononuclear cells exhibited a markedly reduced response to ConA stimulation (≈20% of control) which parallels the reduced proliferative capacity of sarcoid peripheral blood mononuclear cells (≈45% of control). This reduction could be abolished by pretreating the mice with cyclophosphamide. BeSO₄ treatment in combination with incomplete Freund’s adjuvant resulted in a significant increase of spleen mononuclear cell proliferation (1.9-fold) after in vitro stimulation with BeSO₄, and prevented the low responsiveness to ConA. All these findings were maximal after 2 and vanished after 5 weeks. In conclusion, BeSO₄ treatment of mice yields immunological disturbances which parallel some immunopathological phenomena of patients with sarcoidosis.

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Section: Discussionsupporting

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Beryllium-Induced Disturbances of the Murine Immune System Reflect Some Phenomena Observed in Sarcoidosis

Pfeifer

Bartlett²,

Strausz

et al. 1994

Int Arch Allergy Immunol

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“…Lymphokines such as the migration inhibitory factor are released by sensi tized lymphocytes upon exposure to beryllium salts in vitro [22,[24][25][26]. At low concentrations beryllium salts induce antigen-specific lymphocyte blastogenesis in patients with beryllium disease, in some exposed workers, and in exposed animals [10,[27][28][29]. Some other divalent metal ions, such as zinc and mercury, also can induce lymphocyte proliferation in vitro [30][31][32][33] while others are inhibitory (copper, cadmium, cobalt, manganese) [31 ].…”

Section: Discussionmentioning

confidence: 99%

Mitogenic Effect of Beryllium Sulfate on Mouse B Lymphocytes but Not T Lymphocytes in vitro

Newmann

Campbell²

1987

Int Arch Allergy Immunol

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Beryllium metal and its salts can produce disease in man and in animal models. Beryllium disease is thought to involve cell-mediated immunity and an antigen-dependent response by beryllium-specific T cells. Beryllium salts have been shown to stimulate lymphocyte proliferation and release of lymphokines, and to induce granuloma formation and delayed-type hypersensitivity reactions in mice, guinea pigs and man. The studies described here were designed to test the hypothesis that a second lymphocyte population, B cells, may be responding nonspecifically to beryllium. Different populations of BDF₁ mouse lymphocytes were cultured in the presence of varying concentrations of beryllium sulfate (BeSO₄), and the increase in 125-iodouracildeoxyriboside uptake after 72 h in culture was determined. The data show that BeSO₄ is weakly mitogenic for normal mouse spleen cells. Furthermore, BeSO₄ is mitogenic for normal and nude mouse spleen B cells and not for spleen T cells or thymocytes in vitro. These findings suggest that BeSO₄ can stimulate B cells nonspecifically, and support the hypothesis that polyclonal activation of B cells by beryllium may occur.

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“…Simple inorganic ions, such as lithium and beryllium (Williams & Jones Williams, 1982) and a wide variety of more complex organic molecules enhance nucleoside incorporation into lymphocytes stimulated with PHA. They may accomplish this by modifying the normal changes in intracellular cyclic nucleotide concentrations, induced by PHA.…”

Section: Discussionmentioning

confidence: 99%

Effects of therapeutic drugs on lymphocyte transformation.

Williams¹,

Davidson²

1983

Brit J Clinical Pharma

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1 Over 40 non‐steroidal drugs, routinely given on a long term therapeutic basis, were tested in lymphocyte transformation cultures at high therapeutic concentrations, or in serum cultures after short term oral drug administration. Lymphocyte transformation was assessed by measuring thymidine and 2‐deoxyuridine incorporation into DNA. 2 When added in vitro, salicylate significantly inhibited thymidine (48%, n = 35) and deoxyuridine incorporation (20%, n = 12). Thymidine incorporation was specifically inhibited by phenylbutazone (39%, n = 6) and chlorpropamide (48%, n = 5). Specific inhibition of deoxyuridine incorporation, indicative of impaired lymphocyte folate metabolism, was obtained following the addition of pyrimethamine (51%, n = 3) and to some extent by carbimazole (30%, n = 2). In serum cultures, pyrimethamine inhibited deoxyuridine incorporation (30%, n = 3) and chloroquine inhibited the incorporation of both thymidine (37%, n = 3) and deoxyuridine (46%, n = 3). 3 Most classes of drugs used long term are unlikely to cause any significant clinical effect, by impairing lymphocyte function. Caution may be warranted when high doses of salicylate, phenylbutazone, chloroquine, pyrimethamine, chloropropamide or combinations of these drugs are prescribed.

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Development of Beryllium Lymphocyte Transformation Tests in Chronic Beryllium Disease

Cited by 35 publications

References 3 publications

Beryllium-Induced Disturbances of the Murine Immune System Reflect Some Phenomena Observed in Sarcoidosis

Beryllium-Induced Disturbances of the Murine Immune System Reflect Some Phenomena Observed in Sarcoidosis

Mitogenic Effect of Beryllium Sulfate on Mouse B Lymphocytes but Not T Lymphocytes in vitro

Effects of therapeutic drugs on lymphocyte transformation.

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