Analysis of the growth kinetics of murine erythroleukaemia cells following commitment to terminal differentiation

Abstract Differentiation of murine erythroleukaemia cells by various inducers involves a step of irreversible commitment, after which the presence of the inducer is not required for completion of the process. Some cells become partially committed and give rise to differentiated as well as undifferentiated progeny. Commitment occurs asynchronously; under suboptimal inducing conditions, such as low concentration of inducer or short duration of exposure, both committed and uncommitted cells co-exist. In the present study the growth of these subpopulations was compared. Murine erythroleukaemia cells were exposed to the inducer hexamethylene-bisacetamide for 24 hr, then the inducer was removed by washing and the rate of proliferation of committed and uncommitted cells was measured. Commitment was scored by cloning the cells in inducer-free semi-solid medium and determining the cellular composition of the colonies with respect to haemoglobin content. The results indicated that following removal of the inducer the rate of proliferation was retarded similarly for both committed and uncommitted cells. Partially committed cells disappeared rapidly due to assymetrical cell division into fully committed and uncommitted cells. Both committed and uncommitted cells resumed logarithmic growth at 53 hr, but while uncommitted cells continued this pace until saturation was achieved, committed cells stopped multiplying earlier as a result of terminal differentiation.     

Antioxidant effect of diethyldithiocarbamate on microsomal lipid peroxidation assessed by low-level chemiluminescence and alkane production

Different thiol-containing compounds, such as diethyldithiocarbamate (DDC), glutathione, penicillamine, and dithioerythritol have been chosen to study their effect on ascorbate/Fe-ADP-induced lipid peroxidation, detected by low-level chemiluminescence and alkane production. In the concentration range used, these thiols exerted a temporary protection against lipid peroxidation by lengthening the induction period; after overcoming this induction period, no substantial inhibition of either chemiluminescence or alkane production was observed. DDC was effective in protecting against lipid peroxidation in the nanomolar range, whereas the group of other thiol-containing molecules operated in the millimolar range.     

Effect of sodium and chloride depletion on urinary prostaglandin F2α excretion in potassium loaded rats

Previous studies have shown that the urinary excretion of prostaglandin (PG) F2 alpha is stimulated by potassium (K) loading. Because changes of sodium chloride (NaCl) intake also affect renal PG production, in this study we investigated the interaction between the effect of K and that of concomitant reduction of Na and Cl intake. The urinary excretion of PGF2 alpha and PGE2 was measured in 12 groups of female rats on normal, high or low K intake. Na and Cl intake were adjusted so that rats had normal intake (controls, C), were selectively Cl depleted (CD), selectively Na depleted (ND) or Na and Cl depleted (NCD). In rats with normal K intake, urinary PGF2 alpha was not modified by changes of Na or Cl intake, whereas PGE2 was increased in by Cl depletion (in both NCD or CD groups). Potassium chloride loading increased urinary PGF2 alpha and selective Na depletion (ND group) induced a further increase. On the other hand, PGF2 alpha was not stimulated when K load was associated with Cl depletion. Urine PGF2 alpha was directly correlated with plasma aldosterone and urinary kallikrein. Urinary PGE2 did not change with K-loading. The results suggest that PGF2 alpha participates in the renal adaptation to KCl-loading but not when K is accompanied by non-Cl anions.     

Evidence for a single glutamate receptor of the ionotropic kainate/quisqualate type

The kainate (KA) and the quisqualate (QUIS) receptors that activate cation channels in the central nervous system have previously been defined as two of the major glutamate receptor types. In amphibian brain, an exceptionally rich source of these sites, they can be coextracted by octylglucoside and shown to behave as one entity in all analyses made in solution. When partly purified by lectin affinity, ion-exchange chromatography or by sucrose gradient centrifugation, the two activities comigrate in a 1:1 ratio. When the QUIS component is bound to an immobilized specific QUIS agonist, the KA component is extracted in parallel with it. There are equivalent numbers of the QUIS and KA sites and the two sites show a single affinity series for the binding of glutamatergic agonists. We deduce that KA or QUIS select different conformations of a single KA/QUIS receptor binding site, leading thus to the different channel-opening events that have been reported for these two agonists.     

Use of acyclovir in the prevention of herpes infections after allogenic bone marrow grafts

In a double-bind controlled study, oral Acyclovir has been compared to a placebo in a series of 39 consecutive patients undergoing bone marrow transplantation. A dose of 200 mg was given every 6 h from day 8 to day 35 after transplantation. Pharmacokinetic studies have shown the good absorption of the drug despite intestinal damage related to chemoradiotherapy or gut graft-versus-host disease (GVHD), there was no sign of toxicity. The protection against herpes simplex virus (HSV) infection was complete in the treated group when compared to the control group even in patients with high anti-HSV antibody titres. The same protection was observed against cytomegalovirus (CMV) infection. The incidence of HSV and CMV was the same in both groups after treatment ended. This study confirms the efficacy of Acyclovir against HSV infection and possibly against CMV infection when it is given prophylactically after bone marrow transplantation.     

The radiosensitivity of cultured human and mouse keratinocytes

Clonogenic survival assays after gamma-radiation in vitro were performed on freshly isolated and subcultured keratinocytes from mouse skin, mouse tongue and human skin. Survival curves were constructed by fitting the data to a multi-target model of cell survival. When subcultured, keratinocytes from all sites produced survival curves which showed a reduced shoulder region and an increased D0 when compared with their freshly isolated counterparts. Freshly isolated human skin keratinocytes were more radiosensitive than mouse keratinocytes from either skin or tongue.     

A neural-network system for control of eye movements: basic mechanisms

This paper presents a neural-network-based system that can generate and control movements of the eyes. It was inspired by a number of experimental observations on the saccadic and gaze systems of monkeys and cats. Because of the generality of the approach undertaken, the system can be regarded as a demonstration of how parallel distributed processing principles, namely learning and attractor dynamics, can be integrated with experimental findings, as well as a biologically inspired controller for a dexterous robotic orientation device. The system is composed of three parts: a dynamic motor map, a push-pull circuitry, and a plant. The dynamics of the motor map is generated by a multi-layer network that was trained to compute a bidimensional temporal-spatial transformation. Simulation results indicate (1) that the system is able to reproduce some of the properties observed in the biological system at the neural and movement levels and (2) that the dynamics of the motor map remains stereotyped even when the motor map is subject to abnormal stimulation patterns. The latter result emphasizes the role of the topographic projection that connects the motor map to the push-pull circuitry in determining the features of the resulting movements.     

Immunohistochemical and electron microscopic identification of serotonin, melatonin and beta-endorphin in the granules of natural killers

The ability of serotonin, melatonin and beta-endorphin synthesis by secreting granules of natural killer cells (NK cells) was established by immunohistochemical method. It was shown that cytotoxic effect of NK cells can be to a certain extent related to the presence of secreting granules. A possible direct contribution of NK cell-synthesized hormones to the natural killer antitumour effect is discussed.