A H Chalmers

Publications (4)0 Total impact

• Article: Increased calcium absorption in nephrolithiasis explained by uptake studies in ileal brush border membrane vesicles.

  B Ioannoni, A H Chalmers
  [show abstract] [hide abstract]
  ABSTRACT: We previously showed that recurrent calcium renal stone formers have enhanced urinary excretions of calcium and oxalate resulting from malabsorption of citrate. In the present investigation, the mechanism of the citrate-induced increased calcium uptake was studied using guinea pig ileal brush border membrane vesicles. In this model, calcium is absorbed in a concentration dependent, single mechanism uptake with a Km of 275 +/- 30 umol/liter (SD) and a Vmax of 4.0 +/- 0.5 nmol/min.mg protein. Under conditions of maximal calcium uptake, both citrate and phosphate inhibited calcium absorption into brush border membrane vesicles (BBMVs). In contrast, when phosphate and citrate were added together, calcium absorption normalized. Citrate inhibition of calcium absorption appeared to be due to free citrate ions, and phosphate ions overcame this inhibition. Phosphate inhibition was mostly due to decreased concentrations of ionized calcium and partly to precipitation of insoluble calcium phosphate. These studies confirm that the effects of citrate in humans in enhancing calcium absorption occur in the lumen of the gut and are not related to further biochemical conversions of citrate by the gut cells, to effects of citrate on calcium-related hormones, or to the renal handling of calcium. Also, the effects of citrate on increasing calcium absorption should be increased or attenuated in patients who malabsorb citrate, and this explains the increased urinary calcium and oxalate excretions reported for recurrent calcium stone formers.
  Biochemical Medicine and Metabolic Biology 05/1994; 51(2):99-104.
• Article: Tetrandrine and transmembrane signal transduction: effect on phosphoinositide metabolism, calcium flux and protein kinase C translocation in human lymphocytes.

  B Ioannoni, A H Chalmers, W K Seow, J G McCormack, Y H Thong
  [show abstract] [hide abstract]
  ABSTRACT: Time-course and dose-dependent studies showed consistent suppression of phosphoinositide turnover in Con A-stimulated human lymphocytes in the presence of the plant alkaloid, tetrandrine. Significant inhibition of Con A-stimulated calcium flux was also observed. Furthermore, protein kinase C activity was also significantly inhibited by tetrandrine irrespective of whether Con A or phorbol myristate acetate was the stimulant. These results suggest that the immunosuppressive properties of tetrandrine are in part mediated by the capacity of tetrandrine to interfere with transmembrane signalling.
  International archives of allergy and applied immunology 02/1989; 89(4):349-54.
• Article: In vitro immunosuppressive properties of the plant alkaloid tetrandrine.

  W K Seow, A Ferrante, D B Goh, A H Chalmers, S Y Li, Y H Thong
  [show abstract] [hide abstract]
  ABSTRACT: Tetrandrine is an extract of the creeper Stephania tetrandra used in traditional Chinese medicine for the treatment of rheumatic diseases. It has recently been shown to retard and even reverse the lesions of silicosis in humans and rats. Data presented in this report indicate that tetrandrine has potent immunosuppressive properties. Mitogen-induced lymphoproliferative responses were markedly reduced even when tetrandrine was added after the initiation of cultures. In vitro antibody synthesis by B cells was also suppressed by tetrandrine, as was the natural killer cell-mediated lysis of K562 cells. It does not interfere with receptor-ligand binding, but does affect the inositol triphosphate second messenger system. These effects of tetrandrine were observed at nontoxic concentrations as shown by lymphocyte viability studies. These results indicate that tetrandrine possesses potent immunosuppressive properties, and may warrant further study in animal models of chronic inflammatory conditions, autoimmune diseases and transplant rejection.
  International archives of allergy and applied immunology 02/1988; 85(4):410-5.
• Article: Inhibition of histamine release from rat mast cells by the plant alkaloid tetrandrine.

  B S Teh, W K Seow, A H Chalmers, S Playford, B Ioannoni, Y H Thong
  [show abstract] [hide abstract]
  ABSTRACT: The plant alkaloid tetrandrine was shown to have significant inhibitory effects on receptor-ligand-mediated histamine release from rat mast cells at concentrations similar to or lower than that observed with theophylline and sodium cromoglycate. Inhibition of histamine release did not occur when non-specific stimulants such as aspirin, A23187 or adenosine triphosphate were used. Inhibition of ovalbumin-IgE and concanavalin A-mediated histamine release was reversible by washing the cells, showing that tetrandrine does not bind tightly to the cell membrane or cytoplasmic components. These results, taken together with previous reports of its anti-phagocytic, anti-oxidant and immunosuppressive properties, suggest that tetrandrine may be a broad spectrum non-steroidal drug of potential value in the treatment of allergic diseases.
  International archives of allergy and applied immunology 02/1988; 86(2):220-4.