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Biomedical subjects

J Van den Berg

Publications and source records attributed to J Van den Berg.

11 recordsLinked to original sources

BCL-2 expression and mitochondrial activity in leukemic cells with different sensitivity to glucocorticoid-induced apoptosis.

The present study investigates the relationship between mitochondrial activity and the expression of the BCL-2 gene in a panel of six human and murine leukemia/lymphoma cell lines. The cell lines all contained normal glucocorticoid receptors but differed widely in sensitivity to dexamethasone, ranging from very sensitive S49 lymphoma to completely resistant HL-60 acute leukemia cells. In this panel, 10- to 15-fold differences in basal adenosine triphosphate (ATP) content and adenosine diphosphate (ADP)/ATP ratio were correlated with up to fivefold differences in bcl-2 protein (in human cells) and approximately 25-fold difference in bcl-2 mRNA content (all cell lines). Moreover, ATP content and BCL-2 gene expression were inversely correlated with glucocorticoid sensitivity and cell cycle length. In resistant cell lines, sensitivity to dexamethasone was restored by the mitochondrial inhibitors rotenone and meta-iodobenzylguanidine. This sensitization was not accompanied by detectable reductions in bcl-2 mRNA or protein content, suggesting that the inhibitors were capable of overriding BCL-2-mediated inhibition of apoptosis. Increased mitochondrial activity and (overexpressed) BCL-2 appeared closely related properties of glucocorticoid-resistant cells, sharing common cellular targets in hormone-induced apoptosis.

Adenosine Diphosphate

Calf muscle moment, work and efficiency in level walking; role of series elasticity.

Moment and work of the human calf muscles in level walking were determined by means of an EMG to force processor, based on a muscle analogue (Hof and Van den Berg (1981) J. Biomechanics, 14, 747-758, 759-770, 771-785, 787-792). Nine subjects (four women, five men) walked on a level treadmill at speeds between 0.5 and 2.5 ms-1, in their self-chosen pace and at forced pace with steplengths between 0.3 and 1.1 m. The calf muscles are normally only active in the stance phase. The moment increases, with a variable course, to a peak just before push-off. This peak moment increases with the walking speed, from the reference moment (the value in standing on the toes with one leg) at zero speed, to 1.5-2.1 times this value at a speed of 2 ms-1, and decreases at still greater speeds. During the roll-over phase work is done on the calf muscles ('negative work'), followed by positive work in push-off. The negative work is constant, 0.20-0.36 J kg-1, depending on the subject. The positive work increases linearly with steplength--not with speed--from zero at ca. 0.35 m to 0.50 J kg-1 at a steplength of 1.1 m. The interaction between the contractile and the series elastic component in the muscle could be studied by means of the analogue. A great part of the work done on the muscle and of the positive work done by the contractile component are stored in the series elastic component. The stored energy is released at a high rate in push-off. This mechanism ideally requires a concerted contraction, i.e. a contraction in which the activation is matched to the load to the effect that the length of the contractile component remains constant. The muscle then behaves like a spring. Consequences are (a) only little of the negative work gets lost, (b) the length of the contractile component remains close to the optimum of the force-length relation, (c) the shortening speed of the contractile component is now in the range where the muscle works at a high efficiency, and (d) high power peaks can be delivered due to the 'catapult action'.

Adult

Hepatoma cells adapted to proliferate under normally lethal hyperthermic stress conditions show rapid decay of thermoresistance and heat shock protein synthesis when returned to 37 degrees C.

H35 hepatoma cultures were adapted to sustained growth at 41.3 degrees C. In these variant cells the 'basic' levels of various heat shock proteins (hsps), especially those of hsp60, 70 and 100, are significantly raised. These cells exhibit a thermoresistance comparable with the induced thermotolerance in normal hepatoma cells heat shocked at 42.5 degrees C for 30 min. However, this resistance of variant cells shows a rapid, exponential decay with a half-time of 2.2 h when the temperature is lowered to 37 degrees C, with a concomitant decrease of the synthesis of hsp60 and 70. Heat shock experiments with variant cells grown at 41.3 degrees C lead to increased thermoresistance and synthesis of hsps when further incubation was performed at the original temperature but not at 37 degrees C. In the latter case, only a 3-h delay in the onset of decay of thermoresistance is observed. However, when the variant cells were incubated at 37 degrees C prior to heat stress normal induction of thermoresistance and hsp synthesis return inversely proportional to the progression of thermoresistance decay. Thermoresistant cells thus seem to be valuable tools in the study of the down-regulation of thermoresistance as well as of hsp synthesis.

Adaptation, Physiological