Summary Twenty‐two patients with acute myeloid leukaemia were recruited into a phase I/II clinical trial investigating the vaccination of patients in complete remission (CR) with autologous dendritic‐like leukaemia cells (DLLC). At trial entry, leukaemia cells were harvested and tested for their ability to undergo cytokine‐induced dendritic cell differentiation. Patients were then treated with intensive chemotherapy. Five patients achieved both CR and had leukaemia cells that successfully underwent differentiation and therefore proceeded to vaccination. Four escalating doses of DLLC were administered weekly by subcutaneous injection. Vaccination was generally well tolerated although one patient developed extensive eczema and an increased antinuclear factor titre possibly indicating induction of autoimmunity. Development of anti‐leukaemic T‐cell responses was assessed by enzyme‐linked immunospot analysis of gamma‐interferon secreting T lymphocytes and by human leucocyte antigen tetramer analysis for WT1‐specific T cells. Increases in anti‐leukaemic T‐cell responses were demonstrated in four patients, but only two of the five remained in remission more than 12 months postvaccination. The study has demonstrated that generation of DLLC is feasible in only a subgroup of patients and is currently neither broadly applicable or clinically effective.
Extracts of involved and uninvolved skin from nine patients with untreated psoriasis were studied for chemotactic activity. Psoriatic plaque contains increased amounts of a complement-dependent chemotactic factor that is inhibited by diisopropyl fluorophosphate. This factor may be human skin serine proteinase.
Abstract— (1) The effects of thiamine deficiency as produced by pyrithiamine injections have been studied in the weanling mouse. Selected metabolites were measured in extracts from brain and liver of quick‐frozen animals. Pyruvate and α‐oxoglutarate dehydrogenases and transketolase were also measured. (2) In deficient brain, pyruvate and α‐oxoglutarate levels were greatly increased. Xylulose‐5‐P and 6‐P‐gluconate were more than doubled. Lactate, glucose‐6‐P, glucose and P‐creatine were moderately elevated, and ATP was increased a little. Glutamate was depressed. (3) In deficient liver, α‐oxoglutarate was much increased and ATP was twice normal. Glycogen, glucose, glucose‐6‐P, 6‐P‐gluconate, pyruvate, and glutamate were not different from the controls. Lactate was depressed. (4) Pyruvate dehydrogenase activity was reduced to 25 per cent or less in brain and liver. Transketolase and α‐oxoglutarate dehydrogenase activities were reduced to 50 per cent in both organs. (5) Thiamine treatment, within 5 hr, largely reversed the metabolite changes brought on by pyrithiamine in brain. At the same time pyruvate and α‐oxoglutarate dehydrogenase activities were increased 60 per cent or more in both brain and liver. Transketolase activity in liver was only increased 20 per cent at this time, however, and in brain was unchanged. (6) The results are interpreted to indicate that inhibition of pyruvate and α‐oxoglutarate dehydrogenases in brain is sufficient to depress in vivo function. The same seems true for the inhibition of α‐oxoglutarate dehydrogenase in liver. However, the changes seen in brain 6‐P‐gluconate and xyluIose‐5‐P probably depend on factors other than, or in addition to, the decrease in transketolase activity. It seems worthy of emphasis that in spite of the partial metabolic blocks high‐energy phosphate stores were actually increased.
Abstract— The levels of the main cerebral energy reserves, ATP, P‐creatine, glycogen and glucose, and of several glycolytic intermediates and lactate, were measured in the brains of fish (Carassius auratus), turtle (Pseudemys scripta elegans) and frog (Rana pipiens). The levels of glycogen in these brains were 2‐9 times higher than those reported for mammals. In frog, cerebral glycogen levels were 35 per cent higher during the winter than in spring. The P‐creatine: ATP ratios were 3 instead of the more usual (mammalian) value of 1. The levels of other intermediates were similar to those found in mammalian brain. When anoxia was produced by decapitation, changes in the various substances measured were similar to those in mammalian brain, but were much slower. The initial rate at which high‐energy phosphate was used could be calculated from these changes. Values of 1.1 m‐equiv./kg/min for fish and frog and of 0.46 m‐equiv./kg/min for turtle were found, which are 1/20 and 1/50, respectively, of the rate in mouse brain. The rate of disappearance of high‐energy phosphate reserves followed first‐order kinetics for 4 hr in turtle and for at least an hour in the other species. Changes in metabolites as the experiment progressed were interpreted to indicate a progressively falling intracellular pH, prolonged inhibition of phosphofructokinase, and a long period of hexokinase inhibition.
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