Effects of interleukin-12 on natural killer cell cytotoxicity and the production of interferon-7 and tumour necrosis factor-a in patients with myelodysplastic syndromes

The effects of Interleukin 12 (IL-12) on natural killer (NK) cell cytotoxicity and on the production of interferon-7 (IFN-7) and tumour necrosis factor-a (TNF-a) were examined in 15 patients with myelodysplastic syndromes (MDS), which are well known to have immunologic defects, and in 11 normal subjects. The NK cell cytotoxicity of all of the normal subjects was augmented by incubation with IL-12 alone, and co-incubation with interleukin 2 (IL-2) further augmented it (type A response). The MDS patients showed varied responses to IL-12/IL-2. Seven patients showed the type A response, resulting in augmented NK cell cytotoxicity which was similar to that in the normal subjects. In five other patients the cytotoxicity was not increased by IL-12 alone, but the combination of IL-12 and IL-2 did augment the cytotoxicity (type B response). The augmented cytotoxicity in these type B patients was lower than that in the normal subjects. In the final three MDS patients the cytotoxicity was low and not affected by IL- 12 and/or IL-2 (type C response). AH patients with refractory anaemia with excess blasts (RAEB) and patients with RAEB in transformation showed a type B or C response. Conversely, six of eight refractory anaemia patients showed a type A response. In MDS patients there was a positive correlation between the percentage of CD3CD56⁺ cells in pre-incubated cells and the cytotoxicity of cells incubated with IL-12/IL-2. The combination of IL-12 and IL-2 augmented IFN-7 and TNF-Q production by nonadherent mononuclear cells in a synergistic or cumulative manner, respectively, in most patients. These results suggest that IL-12, alone or with IL-2, may modulate these important immunologic functions in most MDS patients.     

Disparity between in vivo and in vitro synthesis of yolk protein by fat bodies of vitellogenic Locusta migratoria after allatectomy

Allatetomy of female locusts at an early stage of oocyte maturation halts subsequent development of terminal oocytes, but this is not due to lack of vitellogenin in the hemolymph. The fat body ceases to secrete vitellogenin in vivo shortly after allatectomy. When excised and incubated in vitro such fat bodies do actively synthesize vitellogenin even 3 days after allatectomy. These results suggest a negative control of vitellogenesis, released as a consequence of allatectomy, and only operative on the fat body in vivo.     

Amine accumulation in behavioural pathology

When nigro-striatal and meso-cortical neurons degenerate there is a loss of dopamine in the terminal fields and an accumulation of amines in the axons of these systems as they traverse the hypothalamus through the medial forebrain bundle. Traditional lines of thought have attributed the occurrence of motor and consummatory deficits which occur after dopamine neuron degeneration to the loss of functional dopamine neurotransmitter in the terminal fields. However we have hypothesized that hypothalamic amine accumulation represents an area of brain tissue where processes such as neurotransmitter release ephaptic transmission or local axon swelling may be affecting adjacent neurons and may thereby participate in the production of behavioural deficits. There is a considerable amount of evidence from studies on both peripheral and central catecholamine-containing neurons indicating that when their axons degenerate a release of functional neurotransmitter can occur. Information from neuropharmacological studies indicates that several drugs which facilitate behavioural recovery from dopamine-depleting lesions may do so by affecting amine release or receptor sensitivity near areas of accumulation rather than depleted terminal fields. We conclude that amine accumulation is a component of dopamine neuron degeneration which should be considered when assessing the role of the central catecholamine systems in the control of various behavioural and physiological processes.     

The effects of guanethidine, bretylium and debrisoquine on the accumulation of noradrenaline in constricted postganglionic sympathetic nerves in vitro

The accumulation of noradrenaline proximal to a constriction applied to cat hypogastric nerves in vitro has been studied in preparations treated with bretylium, guanethidine and debrisoquine. All three drugs reduced the accumulation of the amine. This was paralleled by a decrease in the accumulation of dense vesicles seen with the electron microscope. Evidence is presented which suggests that the drugs e xert a noradrenaline-depleting action upon the amine-storage vesichles. At leat 18 hrs' treatment with bretylium and debrisoquine were necessary before the amine-depleting action of these drugs was evident. It is suggested that the method employed is of value in the correlation of the ultrastructural and biochemical effects of drugs on sympathetic nerves.     

Effects of ingesting 6% and 12% glucose/electrolyte beverages during prolonged intermittent cycling in the heat

Summary This study compared the effects of ingesting 6% (MC) and 12% (HC) glucose/electrolyte beverages, and a flavored water placebo (P) on markers of fluid absorption, palatability, and physiological function during prolonged intermittent cycling in the heat. On three occasions, 15 trained male cyclists performed two 60 min cycling bouts at 65% (E ₁ and E ₂). A brief exhaustive performance ride (3 min) was completed after E ₁ and E ₂, and after 20 min recovery (P ₁, P ₂, P ₃). Every 20 min, subjects consumed 275 mL of P, MC or HC. The first drink contained 20 mL of D₂O, a tracer of fluid entry into blood plasma. Plasma D₂O accumulation was slower for HC than for P and MC (P<0.001). HC caused more nausea (P<0.01) and fullness (P<0.05) than MC or P, and subjects said they would be less likely to consume HC during training or competition (P<0.10). Sweat rates, HR, T _re, T _sk, , and PV were similar for all drinks. Performance of P ₁, P ₂, P ₃ were not different among drinks. However, four cyclists failed to maintain the prescribed work rate during E ₂ for HC but only one failed for MC and P. These data suggest that the slow absorption of a 12% glucose/electrolyte beverage during prolonged intermittent exercise in the heat may increase the risk of gastrointestinal distress and thereby limit performance.     

Electrophoretic patterns of gamma-glutamyltransferase activity eluted from liver tissue.

Up to three zones of gamma-glutamyltransferase activity were present in 89 samples of human serum after agarose-gel electrophoresis at pH 8.6. Their mobilities relative to albumin were zero, 0.3--0.5, and 0.7--0.9. Incubation of human liver tissue in serum increased the activity of the zones with zero and 0.7--0.9 mobilities, and transiently, of the zone of intermediate mobility. More prolonged incubation caused the intermediate zone to decline, and produced new zones of mobility greater than that of albumin which were not seen in native sera. The mobility of partially-purified liver gamma-glutamyltransferase incubated in serum or protein-free solutions was 0.7--0.8. The intermediate zone was not produced when liver tissue was incubated in protein-free solutions, nor with the purified enzyme in serum or protein-free solutions. The possible relevance of these observations to the electrophoretic patterns of gamma-glutamyltransferase in pathological sera is discussed.