significant. However, blood-pressure is not measured routinely in new blood-donors under the age of 50 and it is likely that the control series contains a substantial proportion of actual or potential hypertensives. This might lead to a fairly high incidence of HL-A 12 in the controls and a reduction in the apparent significance of the difference between these two groups, if this antigen is of significance in hypertension. The parallel increase in frequency of W29 in the patients is undoubtedly due to the high degree of positive association that exists between W29 and HL-A 12 (A value 115, Gelsthorpe et al. 4). Thus, we cannot confirm the observation of Low et al. that HL-A 8 is represented excessively in a population of essential hypersensitives. So far we have been unable to identify other points of difference between HL-A 12 hypertensives and those without this antigen and it would be premature to conclude that HL-A 12 is a genetic marker for a subpopulation of essential hypertensives. It would be of interest to hear of similar surveys made in populations of hypertensive patients in other centres. National Blood Transfusion
Centre, Langley Lane, Sheffield 55 7JN.
K. GELSTHORPE R. W. DOUGHTY. R. B. A. S.
Sheffield Hypertension Clinic.
measured as described previously. Enzyme made on six haemolysates as follows: (A) control, with only 0-2 mM Mg++; (B) 0-2 mM Mg++ and 0-2 mM Li+; (C) 0-2 mM Mg++ and 2-0 mM Li+; (D) no Mg++. The accompanying table shows that all four are Mg++ dependent and are not inhibited by enzymes 0-2 mM Li+. With 2 mM Li+, however, enolase activity was reduced from 12-2:1-5 enzyme units to 9.9±1.24 enzyme units (P < 0001); there was no change in the activities of P.F.K., P.G.K., and P.K. In another set of experiments, red blood-cells were incubated for one hour with or without lithium (0-2 mM and 2 mM), washed, and the enzyme accivities were then measured. Again, the enzyme activities of P.F.K., P.G.K., and P.K. did not change. These results confirm our previous suggestion that lithium in the concentration normally found in the tissues during lithium therapy does not inhibit all magnesiumdependent enzymes. Wherever inhibition of enzyme activity has been observed, it may have been due to mechanism(s) other than competition between magnesium and lithium
ions. This work was supported by grants from A.T.N. Channel 7’ the Clive and Vera Ramaciotti New South Wales Foundation, and the Helena Rubinstein Foundation, Inc.
F. BING C. O’MALLEY J. SMITH TALBOT.
LITHIUM AND MAGNESIUM-DEPENDENT ENZYMES SiR,—Although the effect of lithium in preventing depression has been adequately studied and reviewed,5,6 its mode of action is still unknown. It has been demonstrated that lithium inhibits magnesium-dependent enzymes.7-9 However, we found that Li+ did not inhibit the activity of ouabain-sensitive and ouabain-insensitive A.T.p.ases; both enzymes have an absolute requirement for Mg++.10 We have now investigated the effect of lithium on the activities of four glycolytic enzymes of the red blood cells, all of which are dependent on magnesium. The activities of phosphofructokinase (P.F.K.), phosphoglycerate kinase (P.G.K.), pyruvate kinase (P.K.), and Gelsthorpe, K., Doughty, R. W., Davies, P., Bodmer, J. G., Bodmer, W. F. Unpublished. 5. Gattozzi, A. A. National Institute of Mental Health Publication, 5033, Washington, 1970. 6. Gershon, S. Clin. Pharmac. Ther. 1970, 11, 168. 7. Lazarus, L. H., Kitron, N. Lancet, 1974, ii, 225. 8. Birch, N. J. ibid. p. 965. 9. Kadis, B. ibid. p. 1209. 10. Gupta, J. D., Crollini, C. ibid. 1975, i, 216. 4.
Children’s Medical Research
Foundation, Royal Alexandra Hospital for Children, Camperdown, New South Wales, 2050, Australia.
N. S. AGAR MARGARET A. GRUCA
J. D. GUPTA J. D. HARLEY.
NEW SMOKING PRODUCTS
SIR,-May I point out to Dr Harrison (April 19, p. 917) that although cigarette smoking increases morbidity from chronic bronchitis we cannot infer that it must also raise mortality from that disease. Not all patients with chronic bronchitis die from it. The numbers of deaths reported 12 among smoking-discordant twins are as yet insufficient to assess the effects of smoking on mortality from chronic bronchitis. However, when deaths from all causes are considered collectively, the twins studies 12 bave so far failed to implicate smoking as a causal lethal factor. Unaccountably, Dr Harrison chooses to ignore my conclusion (April 5, p. 797), which I should like to repeat: " Thus, there is a case for developing a cigarette that does not cause or exacerbate cough and chronic bronchitis." General Infirmary, Leeds LS1 3EX.
11. Agar, N. S., Smith, J. E. Proc. Soc. exp. Biol. Med. 1973, 142, 502. 12. Friberg, L., Cederlof, R., Lorich, U., Lundman, T., de Faire, U. Archs envir. Hlth, 1973, 27, 294.
EFFECT OF LITHIUM ON THE ACTIVITY OF FOUR GLYCOLYTIC ENZYMES IN THE RED BLOOD-CELLS
Statistical analysis by paired
P. R. J. BURCH.