British Journal of Haematology

Van Rood, J. J.

doi: 10.1111/j.1365-2141.1969.tb00396.xpmid: 5795218

Parry, T. E.

doi: 10.1111/j.1365-2141.1969.tb00397.xpmid: 5795219

Summary: The serum levels of the amino acids, valine and methionine have been determined by a quantitative microbiological method in 17 cases of pernicious anaemia both before and on successive days after treatment. The results have been compared with the serum levels of the two amino acids in 16 normal subjects under similar conditions. The serum valine level is normal in pernicious anaemia in relapse. It falls sharply during the first 48 hours following treatment, thereafter rising gradually to reach about two‐thirds the pretreatment level by the fifth day. This confirms the fall in valine level in whole blood and marrow previously reported in pernicious anaemia under treatment. The serum methionine level is subnormal in pernicious anaemia in relapse. It rises to normal in 48 hours after treatment. Both vitamin B12 and folic acid are effective in lowering the serum valine and elevating the serum methionine. The rise in serum methionine can be explained in terms of the known actions of vitamin B12 and folic acid. The fall in serum valine cannot at present be explained but several possibilities are discussed.

Retief, F. P.; Vandenplas, L.; Visser, H.

doi: 10.1111/j.1365-2141.1969.tb00398.xpmid: 4183533

Summary: Vitamin B12 binding proteins were studied in patients with acute and chronic liver disease, and compared with vitamin B12 binders in chronic myeloid leukemia. In acute viral hepatitis marked elevation of serum vitamin B12 was common. Although the serum vitamin B12 rose as high as that found in chronic myeloid leukaemia the unsaturated vitamin B12 binding capacity (UBBC) was markedly elevated in the latter condition, whereas it was decreased in acute liver disease. In cirrhosis a moderate increase of serum vitamin B12 and UBBC was common. Urinary vitamin B12 excretion increased significantly only when the serum vitamin B12 became markedly elevated in hepatitis. As in chronic myeloid leukaemia the alpha‐globulin vitamin B12‐binder carried the bulk of the elevated serum vitamin B12 in acute liver disease; the beta‐globulin vitamin B12‐binder was decreased in serum but seemed to be the predominant binder in urine. This suggests that renal loss of beta‐globulin binder is greater than renal loss of alpha‐globulin binder. Only minor albumin binding of vitamin B12 in liver disease was found in spite of marked elevation of the serum vitamin B12 level. In cirrhosis the serum alpha‐globulin binder was often increased and beta‐globulin binder decreased. The cause and significance of these findings are discussed. The ability of serum vitamin B12‐binders of liver disease to ‘transfer’57Co‐B12 to tissue was investigated in an in vitro rat liver homogenate system. In a limited study, vitamin B12 uptake appeared to be within normal limits, except for suboptimal uptake from the beta‐globulin binder in cirrhotic serum. Poor vitamin B12 uptake from chronic myeloid leukaemia serum (in particular alpha‐globulin binder) was confirmed.

Hefner, G. W.

doi: 10.1111/j.1365-2141.1969.tb00399.xpmid: 5795220

Summary: Absorption of crystalline folic acid (pteroylglutamic acid—PGA) was studied in rats, using tritiated PGA and an in vivo absorption technique. Increasing doses of PGA were introduced into the jejunum and ileum: the percentage absorption fell with increasing doses in the jejunum, suggesting the presence of an active transport mechanism, whereas percentage absorption in the ileum remained constant for all doses, suggesting that absorption occurred by passive diffusion. Phenytoin and methotrexate put into the jejunum immediately before PGA partly inhibited its absorption, as did subcutaneous methotrexate given 3 hours before the PGA was administered. Methotrexate had no effect on the ileal absorption of PGA, nor on the absorption of D‐xylose in the jejunum.

Weatherall, D. J.; Clegg, J. B.; Na‐Nakorn, Supa; Wasi, Prawase

doi: 10.1111/j.1365-2141.1969.tb00400.xpmid: 5795221

Summary: The rate of globin chain production has been studied in patients with homozygous β‐thalassaemia, heterozygous β‐thalassaemia, haemoglobin E‐thalassaemia, and sickle‐cell‐thalassaemia, and compared with that in non‐thalassaemic individuals. A partial or total deficit of β‐chain synthesis has been demonstrated in all forms of β‐thalassaemia. This results in the production of a large intracellular pool of α‐chains, the kinetics of which have been worked out. The α‐chains in this pool appear to contain haem and are unstable, rapidly becoming associated with the stromal fraction. These findings are examined in terms of the pathogenesis of the anaemia of thalassaemia.

Sirchia, G.; Ferrone, S.; Mercuriali, F.

doi: 10.1111/j.1365-2141.1969.tb00401.xpmid: 4978548

Summary: The complement (c′) titre, the concentration of the third component of C’ (c′3) and the capacity of sera to lyse PNH cells in the acidified‐serum test and the sugar‐haemolysis test have been determined on the sera obtained from 100 healthy subjects and 103 patients with cirrhosis of the liver. The lytic capacity of normal sera for PNH cells is not correlated with the serum's C'titre or c′3 concentration. With cirrhotic sera, however, a significant correlation was found between c′3 concentration and PNH haemolytic capacity, especially in the sugar‐haemolysis test. It is concluded that, under certain conditions, c′3 can be rate‐limiting in PNH cell lysis in vitro.

Gröttum, Kjell A.; Solum, Nils Olav

doi: 10.1111/j.1365-2141.1969.tb00402.xpmid: 4893927

Summary: Three patients with congenital macrothrombocytic thrombocytopenia are described. The platelets had a reduced electrophoretic mobility, and the content of sialic acid was also abnormally low, suggesting a defect in the platelet membrane. Platelets were rapidly removed from the circulation, possibly because the platelet membrane defect was associated with reduced electrostatic repulsive forces.

Prentice, C. R. M.; Ratnoff, Oscar D.

doi: 10.1111/j.1365-2141.1969.tb00403.xpmid: 5815894

Summary: The effect of Russell's viper venom on Factor V was studied. It was found that the venom greatly increased the activity of Factor V and that the reaction was not dependent on the presence of calcium ions. This action appeared to be responsible for the time‐consuming reaction between activated Factor X and Factor V noted previously. When the venom was neutralized with a specific antiserum after Factor X had been activated, this time‐consuming reaction was no longer noted. Factor V, treated with Russell's viper venom, was not able by itself to convert pro‐thrombin to thrombin, and could not therefore be regarded as the final prothrom‐bin‐converting principle. The prothrombin‐converting principle, containing activated Factor X, Factor V, phospholipid and calcium was able to generate thrombin from prothrombin more rapidly when Factor V had been treated with venom than when it was untreated. The explanation for this was that, in the presence of untreated Factor V, there was a lag period before detectable thrombin appeared when the principle was added to prothrombin. When Factor V had been pre‐treated with venom, thrombin generation started immediately. In this respect, there was a similarity in action between thrombin and Russell's viper venom on Factor V. It was concluded that the venom has an action on at least two clotting factors, namely X and V, and for this reason caution must be used in interpreting the results of laboratory tests involving its use.

Dreyfus, B.; Sultan, C.; Rochant, H.; Salmon, Ch.; Mannoni, P.; Cartron, J. P.; Boivin, P.; Galand, C.

doi: 10.1111/j.1365-2141.1969.tb00404.xpmid: 4240220

Summary: Blood‐group antigens and erythrocyte glycolytic enzyme activities were studied in II cases of refractory anaemia consisting of seven cases of refractory anaemia with excess of myeloblasts in bone marrow and four cases of acquired sideroblastic anaemia. Some significant modifications of the amounts of A, A1, B, H, I and i antigens were found in 10 cases. Some enzyme deficiencies involving pyruvate kinase, 2–3‐diphosphoglycerate mutase and phosphofructokinase were observed. In addition, several populations of pathological red cells showing distinct antigenic abnormalities were demonstrated in one patient. A new type of anaemia with acquired multiple and varied enzyme anomalies of the red‐cell series has therefore been defined. Its links with acute leukaemia are discussed.

Caron, G. A.

doi: 10.1111/j.1365-2141.1969.tb00405.xpmid: 5795222

Summary: DNA synthesis, measured by tritiated thymidine uptake during the final 1 hour in vitro, has been used as a measure of blast transformation of human peripheral small lymphocytes cultured in media containing 20 per cent autologous plasma. Control cultures from two subjects of up to 12 and 15 days duration and from eight further subjects of 3 and 6 days duration have been studied and the degree of spontaneous transformation compared to the response to known stimulants of transformation, phytohaemagglutinin and specific antigens. Spontaneous transformation was consistently low for up to 6 days. Thereafter there was a relatively slight increase. Theoretical arguments why the increased proportion of labelled cells found in some of the older cultures may be an artifact of differential cell survival are presented. Review of previous reports of spontaneous lymphocyte transformation suggests that this is minimal when the cells are cultured in autologous plasma and that heterologous sera may act as an unsuspected transformation stimulant.