PubMed · 14129389
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L R BRYANT, J H WULSIN, W A ALTEMEIER. 1964. HYPERPARATHYROIDISM AND HYPERTHYROIDISM.. https://doi.org/10.1097/00000658-196403000-00014
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It is now a well-known fact that alpha-CD (alpha-cyclodextrin) and Ca(2+) are two important folding agents in the re-activation and refolding processes of many denatured enzyme solutions. Bacillus sp. alpha-amylase was extensively denatured in a 6 M guanidinium chloride solution overnight. Under suitable renaturation conditions, 20-30% more activity was recovered in the presence of various concentrations of alpha-CD (0-100 mM). Similarly, 25-30% more activity was recovered under the influence of different concentrations of Ca(2+) (0-100 mM). Regardless of these results, both alpha-CD and Ca(2+) at 100 mM concentrations were separately capable of preventing the extent of aggregate formation by 86 and 77% respectively. These observations clearly indicate that the effects of alpha-CD and/or Ca(2+) on the process of aggregation and refolding (activity recovery) are not synchronized: both agents mostly act as anti-aggregatory agents instead of acting as refolding agents.
Polyoxidonium (PO) is a high-molecular weight physiologically active compound with pronounced immunomodulating activity, an N-oxidized polyethylene-piperazine derivative. The aim of our work was to study cellular and molecular mechanisms of the action of PO on the human peripheral blood leukocytes. By means of flow cytometry it was established that the binding of fluorescein-isothiocyanate-labeled PO (FITC-labeled PO) occurs more rapidly with monocytes and neutrophils than with lymphocytes (7- to 8-fold weaker as compared with monocytes). Using colloidal gold-labeled PO and electron microscopy it was shown with that the preparation penetrates into leukocytes by endocytosis. PO is localized in endoplasmic vesicles of cellular cytosol. Analysis of one of the crucial signal transducer, the intracellular Ca(2+), performed with the Fluo-3 fluorescent dye, showed that PO does not induce Ca(2+) mobilization from the intracellular calcium stores and influx of extracellular Ca(2+). The study of the intracellular hydrogen peroxide (H(2)O(2)) production with the 2',7'-dichlorfluorescein indicator demonstrated that PO significantly increases the level of intracellular H(2)O(2) in monocytes and neutrophils, however, this increase is much less as compared with phorbol myristate acetate stimulation. The analysis of immunomodulating effect produced by PO proved its stimulating activity on some cytokines production in vitro, e.g. interleukin 1beta (IL-1beta), tumor necrosis factor (TNF)-alpha and IL-6. A dose-dependent increase in the intracellular killing by blood phagocytes was established under the action of PO.
The causes of Darier disease (DD) and Hailey-Hailey disease (HHD) have eluded clinicians and scientists for more than 60 years. DD is characterized by loss of adhesion between suprabasal epidermal cells associated with abnormal keratinization, while loss of epidermal cell-to-cell adhesion is predominant in HHD. The genes for both conditions have recently been identified using candidate positional cloning approaches. The gene for DD (ATP2A2) encodes a calcium transport ATPase of the sarco (endo)plasmic reticulum (SERCA2) Verboomen et al. [1992: Biochem J 286(Pt 2):591-595], while the gene for HHD (ATP2C1) codes for a secretory pathway for calcium and manganese transport ATPase of the Golgi apparatus (SPCA1) Hu et al. [2000: Nat Genet 24:61-65]. These results have provided completely new insights into the role of calcium and/or manganese in maintaining skin integrity. Although the precise disease mechanisms remain to be understood, these discoveries open a new field in research for the understanding and the treatment of these distressing disorders.