Histamine release from rat mast cells induced by the metabolic activation of drugs of abuse into free radicals

Techniques such as positron-emission tomography, single-photon-emission computed tomography, functional magnetic-resonance imaging and magnetoencephalography permit the observation of biological processes in the brain in a noninvasive manner. They have yielded new insights into the biological interrelations of sensory, motor and cognitive functions, as well as into brain diseases. Combined use of these techniques may provide more information than just the sum of its constituents, and this may narrow the gap between the biological data provided by these techniques and the mental models described by clinicians, mathematicians, psychologists and philosophers.     

10 kHz-linewidth diode-pumped Er:Yb:glass laser

A single-mode Er:Yb:phosphate glass laser pumped at 980 nm by an InGaAs diode laser is reported. The laser emits over 15 mW output power with 6% slope efficiency. The measured linewidth is 10.6 kHz and the RIN power is less than 140 dB/Hz.<>     

MPEG-4-based error resilient coding with closed-loop interaction among peripheral and centralised processing modules

Proposed is a novel MPEG-4-based video coding the resilience of which is implemented by exploiting region-of-interest scalability together with a closed-loop interaction between a central processing system, devoted to object detection and tracking, and the video coding embedded at sensor level. Results in terms of processing reliability, achieved in a formal way, prove the usefulness of the proposed approach in the context of scene monitoring applications     

Leucine transport in Xenopus laevis oocytes: functional and morphological analysis of different defolliculation procedures

L-leucine uptake in stage V Xenopus laevis oocytes was affected by the specific methods used to remove the follicle cells. In the presence of 100 mM NaCl, L-leucine uptake was reduced by 67.5% +/- 5.7 when defolliculation was performed enzymatically by collagenase treatment, whereas the reduction was 30.5% +/- 6.4 after mechanical defolliculation. The Na(+)-dependent uptake of 0.1 mM L-leucine was 18.6 +/- 4.6 pmol oocyte-1 40 min-1 in folliculated oocytes and 5.6 +/- 1.9 in collagenase defolliculated oocytes (means +/- SE). L-leucine uptake was not affected by the removal of the follicular layer if defolliculation occurred after the transport period; radiolabeled L-leucine is therefore not taken up into a compartment that is removed by the defolliculation process. The different L-leucine uptake rates observed in folliculated and defolliculated oocytes were not due to non-specific L-leucine binding to membranes. L-leucine kinetics showed that the L-leucine Vmax and Km values were lower in oocytes deprived of the follicular layer than in control oocytes enveloped in intact follicular layers. The Vmax and Km values of Na(+)-dependent L-leucine transport, calculated from data obtained the day after defolliculation by collagenase treatment, were: 16 +/- 1.5 pmol oocyte-1 40 min-1 and 57 +/- 21 mumol (mean +/- SD). The Na(+)-activation curve of 0.1 mM L-leucine was hyperbolic in folliculated oocytes and sigmoidal in defolliculated oocytes. The morphological analysis performed in parallel with the transport experiments showed that after defolliculation, the fibers forming the vitelline membrane tended to be arranged in a more regular orthogonal array, and the number of oocyte microvilli was reduced after collagenase treatment. Mechanical defolliculation did not appreciably affect the oocyte microvilli, however this procedure did not completely remove all follicle cells. The damage to collagenase treated oocytes was reversible, and the functional and structural features of most oocytes improved upon subsequent in vitro incubation. The recovery process seemed to involve protein synthesis in view of the increased value of L-leucine Vmax, and microscopic observation showing recovery of the microvillar apparatus.     

Wt-p53 action in human leukaemia cell lines corresponding to different stages of differentiation

Recent studies support the potential application of the wt-p53 gene in cancer therapy. Expression of exogenous wt-p53 suppresses a variety of leukaemia phenotypes by acting on cell survival, proliferation and/or differentiation. As for tumour gene therapy, the final fate of the neoplastic cells is one of the most relevant points. We examined the effects of exogenous wt-p53 gene expression in several leukaemia cell lines to identify p53-responsive leukaemia. The temperature-sensitive p53Val135 mutant or the human wt-p53 cDNA was transduced in leukaemia cell lines representative of different acute leukaemia FAB subtypes, including M1 (KG1), M2 (HL-60), M3 (NB4), M5 (U937) and M6 (HEL 92.1.7), as well as blast crisis of chronic myelogenous leukaemia (BC-CML: K562, BV173) showing diverse differentiation features. By morphological, molecular and biochemical analyses, we have shown that exogenous wt-p53 gene expression induces apoptosis only in cells corresponding to M1, M2 and M3 of the FAB classification and in BC-CML showing morphological and cytochemical features of undifferentiated blast cells. In contrast, it promotes differentiation in the others. Interestingly, cell responsiveness was independent of the vector used and the status of the endogenous p53 gene.     

Effect of dietary versus pharmacological correction of hypertriglyceridemia on red blood cell membrane sodium/lithium countertransport activity

An elevated red blood cell Na/Li countertransport (Na/Li CT) is often associated with high blood pressure and metabolic abnormalities. Recent studies suggested that a reduction in serum TG levels is associated with a decrease in Na/Li CT activity. However, it is still unclear if this phenomenon could be originated from systemic metabolic alterations or from modifications of the membrane dynamic properties. Aim of the present study was to investigate whether dietary or pharmacological TG lowering therapy might have a different effect on Na/Li CT activity and related metabolic parameters. Twenty normotensive hyper-TG patients were recruited from the Lipid outpatient Clinic: they had a baseline Na/Li CT activity significantly higher compared with age- and BMI-matched normolipidemic controls (386+/-33 vs 274+/-39 umol/l RBC/h, p<0.05). The patients were randomly prescribed one of the following two-months treatment: Group 1)-triglyceride lowering diet; Group 2)-lipid lowering drug (Gemfibrozil 600 mg b.i.d.). Na/Li CT and metabolic and anthropometric variables were measured at baseline and after 1 and 2 months of treatment. At the end of intervention, there was in both groups a significant and comparable fall in plasma triglyceride (group 1: -2.61+/-0.73 mmol/l p<0.01; group 2: -4.29+/-1.20 mmol/l p<0.01). In the diet-treated group there were, in addition small but significant reductions in body weight (-3.7+/-0.8 kg p<0.01), fasting glucose (-0.36+/-0.14 mmol/l p<0.05) and insulin levels (-2.1+/-0.5 mU/l, p<0.01), while no such changes were observed in the fibrate treated patients. Na/Li CT activity was significantly and comparably reduced at the end of treatment in both groups (group 1: -97+/-28 umol/l cell/h, p<0.01; group 2: -89+/-30 umol/l cell/h, p<0.01). In conclusion, these results indicate that the decrease in Na/Li CT associated with both dietary and drug treatment of hypertriglyceridemia is to be traced to a direct effect of plasma TG concentration on this transport system (probably as a result of modification in the membrane lipid environment) rather than to changes in plasma insulin levels or insulin resistance.     

Long-term follow-up results of alpha-interferon-based regimens in patients with late chronic phase chronic myelogenous leukemia

The aim of this analysis was to evaluate the efficacy of alpha-interferon (alpha-IFN) regimens in late chronic phase (diagnosis >12 months) chronic myelogenous leukemia (CP-CML). Long-term follow-up results were evaluated in 137 patients with Philadelphia chromosome (Ph)-positive late CP-CML. The alpha-IFN programs were sequential studies with human leukocyte alpha-IFN (seven patients), recombinant alpha-IFN alone (15 patients) or with IFN-gamma (29 patients), hydroxyurea (HU) (19 patients), or low-dose cytarabine (Ara-C) (67 patients). Overall, 57% of the patients achieved complete hematological response (CHR), and 7% obtained partial hematological response. Nineteen patients (15% of the 123 evaluable patients) had a cytogenetic response which was major (Ph-positive <35%) in 10 patients (8%). A trend for better responses was observed with shorter disease duration. The median overall survival from start of therapy was 49 months, with an estimated 5-year survival rate of 41%. Some common pretreatment prognostic factors associated with response did not show statistical associations when applied in late CP-CML; however, characteristics such as smaller spleen size, and lower percentages of peripheral blood and marrow blasts and basophils were associated with better survival experience. When patients were subgrouped according to risk, no significant differences in the incidence of cytogenetic response and in survival outcomes were observed among various risk groups. This study confirms that alpha-IFN-based regimens have a modest activity in late CP-CML, and supports the need to develop investigational strategies aimed at improving patient prognosis in this phase.     

Synaptic current at the rat ganglionic synapse and its interactions with the neuronal voltage-dependent currents

The membrane current activated by fast nicotinic excitation of intact and mature rat sympathetic neurons was studied at 37 degrees C, by using the two-microelectrode voltage-clamp technique. The excitatory postsynaptic current (EPSC) was modeled as the difference between two exponentials. A fast time constant (tau2; mean value 0.57 ms), which proves to be virtually voltage-independent, governs the current rise phase and a longer time constant (tau1; range 5.2-6.8 ms in 2 mM Ca2+) describes the current decay and shows a small negative voltage dependence. A mean peak synaptic conductance of 0.58 muS per neuron is measured after activation of the whole presynaptic input in 5 mM Ca2+ external solution (0.40 muS in 2 mM Ca2+). The miniature EPSCs also rise and decay with exponential time constants very similar to those of the compound EPSC recorded at the same voltage. A mean peak conductance of 4.04 nS is estimated for the unitary event. Deconvolution procedures were employed to decompose evoked macrocurrents. It is shown that under appropriate conditions the duration of the driving function describing quantal secretion can be reduced to <1 ms. The shape of the EPSC is accurately mimicked by a complete mathematical model of the sympathetic neuron incorporating the kinetic properties of five different voltage-dependent current types, which were characterized in a previous work. We show that IA channels are opened by depolarizing voltage steps or by synaptic potentials in the subthreshold voltage range, provided that the starting holding voltage is sufficiently negative to remove IA steady-state inactivation (less than -50 mV) and the voltage trajectories are sufficiently large to enter the IA activation range (greater than -65 mV). Under current-clamp conditions, this gives rise to an additional fast component in the early phase of membrane repolarization-in response to voltage pulses-and to a consistent distortion of the excitatory postsynaptic potential (EPSP) time course around its peak-in response to the synaptic signal. When the stimulation initiates an action potential, IA is shown to significantly increase the synaptic threshold conductance (up to a factor of 2 when IA is fully deinactivated), compared with that required when IA is omitted. The voltage dependence of this effect is consistent with the IA steady-state inactivation curve. It is concluded that IA, in addition to speeding up the spike repolarization process, also shunts the excitatory drive and delays or prevents the firing of the neuron action potential.