Bladder toxicity with chronic oral cyclophosphamide therapy in nonmalignant disease.
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Biomedical subjects
Publications and source records attributed to J P Atkinson.
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This report is devoted to methodologies used in analyzing the C3b/C4b receptor (CR1, CD35) on erythrocytes (E), its soluble form, the CRI structural or allotype polymorphism, and CR1 density polymorphism. In primates E CR1 serves as the main system for processing and clearance of complement opsonized immune complexes (IC). CR1 copy numbers decrease with aging of E in normal individuals. Erythrocyte CR1 is also decreased in pathological conditions such as systemic lupus erythematosus (SLE), HIV infection, certain hemolytic anemias, and many other conditions featuring immune complexes. Consequently, CRI on E has an important physiological role in immune complex handling and has interesting alterations in disease.
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Heparin solutions containing benzyl alcohol as a preservative increase intracellular cAMP concentrations in human lymphocytes by as much as 5 fold. Similar changes but of a lesser magnitude were also observed in human polymorphonuclear leukocytes and platelets and rabbit alveolar macrophages. Further analysis demonstrated that benzyl alcohol used as a preservative was responsible for this finding and that heparin per se had no effect on cAMP metabolism. The cAMP response to benzyl alcohol was a time- and dose-dependent process. In human peripheral blood lymphocytes, cAMP levels increased in a linear fashion over a benzyl alcohol concentration range from 0.015-0.30% (v/v). The increased cAMP concentrations in lymphocytes as measured by radioimmunoassay were not due to formation of a cross-reacting adenosine-alcohol adduct since the immunoreactive material produced was destroyed by phosphodiesterase and co-migrated with 3H-cAMP in thin layer chromatographic studies. Concentrations of benzyl alcohol which affect cAMP metabolism are commonly present in biologic studies employing heparin solutions. In view of these findings certain previously described effects of heparin may need to be reinterpreted and in the future heparin solutions containing benzyl alcohol should not be used when studying biologic processes known to be influenced by alterations in cAMP metabolism.
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The recognition of the association between complete and partial complement (C) deficiencies and immune complex (IC) mediated diseases, especially SLE, is of clinical and etiopathologic interest. From studies of sera deficient in C1, C4, C2 or C3, the crucial role of these components of the classical pathway in promoting the solubility and clearance of IC has been elucidated. Although complete deficiency of C1, C4 C2 or C3 is rare, partial C4 deficiency also appears to be a common predisposing factor for the development of SLE, with complete C4A deficiency (C4A null) being present in 10 to 15% and heterozygous C4A deficiency present in 50 to 80% of caucasian SLE patients. Most importantly, there is an obvious pathophysiologic relationship between the function of C relative to IC processing and the syndromes which result from C deficiency. Thus, SLE is a prototype for disease characterized by excessive quantities of inappropriately deposited IC. More subtle C component and receptor deficiencies are likely to be predisposing factors for SLE and related autoimmune diseases.