THE EFFECTS OF CHANGES IN AROUSAL LEVEL ON CRITICAL FLICKER FUSION FREQUENCY AND FIGURAL REVERSAL TASKS

The present study was designed to investigate the relationship between intra-and inter-individual differences in arousal level and performance on both critical flicker fusion frequency and figural reversal tasks. Forty male undergraduate Ss were used. Electrical skin conductance was used as the indicant of arousal level. For the intra-individual comparisons white noise was used to increase the Ss’arousal levels. Significant inverted U-shaped relationships were found between both flicker fusion thresholds and rates of figural reversal and skin conductance between individuals. A significant curvilinear relationship was found between rates of figural reversal and level of conductance within individuals. No significant curvilinear relationship was found between flicker fusion thresholds and level of conductance within individuals.     

Retention of successive position reversals in rats with septal and fronto-polar lesions

Eight successive position reversals were given preoperatively to establish position reversal sets in rats. Six animals received septal lesions, six fronto-polar cortex ablations, and six normals served as a control group. During a series of eight postoperative reversals, rats with septal lesions committed significantly more errors and approach errors than normals while fronto-polar ablations had no detectable effect.     

模式翻转视觉诱发电位快速提取的可行性再研究

目的把模式翻转视觉诱发电位快速提取法应用于视神经病变的病人,探讨其临床应用价值。方法应用Galileo视觉诱发电位检测系统对30例正常健康人和17例视神经疾病病人分别进行全视野的PRVEP检测熏每一结果重复检测3次。所得结果应用少次提取法进行处理而得VEP波形。然后将正常对照组3次重复结果两两间分别进行配对t检验,探讨其可重性,并计算出正常值范围,最后参照正常值,分析视神经疾病组的检测结果。结果3次重复结果两两间配对t检验,得P1=0.425>0.05,P2=0.179>0.05,P3=0.110>0.05;参照本研究得出的正常值范围,对病人组的检测结果进行分析,得出这种少次提取法对视神经疾病检测的敏感度90.0%(18/20),特异度92.5%(13/14),准确度91.1%(31/34)。结论用这种少次提取法提取PRVEP,可重性好,稳定可靠。很有临床应用价值。     

Potent induction of human colon cancer cell uptake of chemotherapeutic drugs by N-myristoylated protein kinase C-α (PKC-α) pseudosubstrate peptides through a P-glycoprotein-independent mechanism

Phorbol ester protein kinase C (PKC) activators and PKC isozyme over-expression have been shown to significantly reduce intracellular accumulation of chemotherapeutic drugs, in association with the induction of multidrug resistance (MDR) in drug-sensitive cancer cells and enhancement of drug resistance in MDR cancer cells. These observations constitute solid evidence that PKC plays a significant role in the MDR phenotype of cancer cells. PKC-catalyzed phosphorylation of the drug-efflux pump P-glycoprotein was recently ruled out as a contributing factor in MDR. At present, the sole drug transport-related event that has been identified as a component of the role of PKC in MDR is PKC-induced expression of the P-glycoprotein-encoding gene mdr1. The objective of this study was to test the hypothesis that PKC can modulate the uptake of chemotherapeutic drugs in cancer cells independently of P-glycoprotein. We analyzed the effects of selective PKC activators/inhibitors on the uptake of radiolabelled cytotoxic drugs by cultured human colon cancer cells that lacked P-glycoprotein activity and did not express the drug efflux pump at the level of message (mdr1) or protein. We found that the selective PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) significantly reduced uptake of [¹⁴C] Adriamycin and [³H] vincristine in human colon cancer cells devoid of P-glycoprotein activity, and that PKC-inhibitory N-myristoylated PKC- pseudosubstrate synthetic peptides potently and selectively induced uptake of the cytotoxic drugs in the phorbol ester-treated and non-treated colon cancer cells. TPA treatment of the cells did not induce expression of either P-glycoprotein or its message mdr1. In contrast with [¹⁴C]Adriamycin and [³H] vincristine uptake, [³H] 5-fluorouracil uptake by the cells was unaffected by TPA and reduced by the PKC-inhibitory peptides. These results indicate that PKC activation can significantly reduce the uptake of multiple cytotoxic drugs by cancer cells independently of P-glycoprotein, and that N-myristoylated PKC- pseudosubstrate peptides potently and selectively induce uptake of multiple cytotoxic drugs in cultured human colon cancer cells by a novel mechanism that does not involve P-glycoprotein and may involve PKC isozyme inhibition. Thus, N-myristoylated PKC- pseudosubstrate peptides may offer a basis for the development of agents that reverse intrinsic drug resistance in human colon cancer.     

Excitatory amino acid release from astrocytes during energy failure by reversal of sodium-dependent uptake

Non-synaptic release may be the major route of excitatory amino acid (EAA) efflux during cerebral ischemia. Possible routes of non-synaptic release include non-specific anion channels, reversal of Na⁺-, CI^?-, or Ca²⁺-dependent uptake, and cell lysis. In the present study we employ a novel approach to show reversal of Na⁺-dependent uptake as a major route of EAA efflux from astrocyte cultures under conditions of energy failure. Primary rat astrocyte cultures were subjected to combined blockade of glycolytic and oxidative metabolism after incubation with [³H]-D-aspartate (D-ASP). Energy failure produced an efflux of D-ASP that was maximal by 90 minutes. The efflux over this period was reduced by more than 50% in cells that had been pre-loaded with PDC (L-transpyrrolidine-2,4-dicarboxylic acid) or TBHA (threo-β-hydroxyaspartic acid), compounds that are competitive inhibitors of Na⁺-dependent glutamate uptake. The effect of pre-loading with the inhibitors was concentration dependent. No effect was seen if the inhibitors were added after induction of energy failure, suggesting that the attenuation of D-ASP efflux resulted from binding of the inhibitors to an intracellular site. These results provide strong evidence that EAA efflux from astrocytes under conditions of energy failure occurs largely through reversal of Na⁺-dependent uptake. © 1995 Wiley-Liss, Inc.

1 This article is a US Government work and, as such, is in the public domain in the United States of America.

     

Discriminative power of visual evoked potential characteristics in multiple sclerosis

To investigate the discriminative power of pattern-reversal visual evoked potential characteristics (peak latencies and amplitude) and to test whether the addition of visual evoked potential amplitude can increase the power of the visual evoked potential in the diagnosis of multiple sclerosis, we retrospectively studied visual evoked potentials in 59 patients with definite multiple sclerosis and 126 control subjects. Two check sizes (17 and 10) were used. Females had significantly higher amplitudes and shorter latencies than males. N80 latency showed a gradual increase and P100 amplitude a decrease with age. P100 latency was stable between the ages of 20 and 55 years but was increased in childhood and the elderly. The significance of visual evoked potential peak latencies and amplitude in separating the two groups was investigated by means of a (multivariate) discriminant analysis. The visual evoked potential with a pattern of 10 could be measured in 58% of patients with multiple sclerosis. The exclusive use of the P100 amplitude in the discriminant analysis resulted in a percentage of correctly classified cases of 84%, whereas for P100 and N80 latency it was 85% and 90%, respectively. With the 17 pattern, the N80 latency yielded also a higher correct percentage than did the P100 latency. Although N80 latency is, to a greater extent than P100 latency, influenced by age, sex and size of stimulus pattern, when these influences are accounted for, the N80 latency is a more sensitive measure than P100 latency in the classification of multiple sclerosis. Combined use of latency and amplitude for discriminant analysis yielded no significant improvement of the percentage of correctly classified cases.Abbreviations MS multiple sclerosis - SD standard deviation     

Early postnatal maturation of GABAA-mediated inhibition in the brainstem respiratory rhythm-generating network of the mouse

It is well established that GABA_A‐mediated postsynaptic potentials are excitatory in many brain regions during embryonic and early postnatal life. The pre‐Bötzinger complex (PBC) in the brainstem is an essential component of the respiratory rhythm‐generating network, where GABA_A‐mediated inhibition plays a critical role in generating a stable respiratory rhythm in adult animals. In the present study, using the perforated patch technique, we investigated the maturation of GABA_A receptor‐mediated effects on rhythmically active PBC neurons and on the motor output in slice preparations from P0–15 neonatal mice. The reversal potential of GABA_A receptor‐mediated current (E_GABA‐A) switched from depolarizing to hyperpolarizing within the first postnatal week. E_GABA‐A was ?13.7 ± 9.8 mV at P0, then it changed to ?44.8 ± 7.0 mV at P2 and ?71.5 ± 6.8 mV at P4. Perfusion of bicarbonate‐free saline has no detectable influence on E_GABA‐A, indicating that a lack of Cl^– extrusion during P0–3 is mainly responsible for early GABA_A‐ergic excitation. At the network level, blockade of GABA_A receptors with bicuculline did not significantly change the frequency of rhythmic bursts recorded from hypoglossal nerve roots before P3, whereas it increased the coefficient of variation. After P3, bicuculline increased burst frequency with little effect on the coefficient of variation. Thus, chloride‐mediated inhibition, which appears in PBC neurons after P3, coincides with the appearance of GABA_A‐mediated modulation of the respiratory rhythm. GABA_A receptor‐activated inhibition may therefore be necessary for frequency modulation in the respiratory network beginning on the fourth postnatal day in the mouse brainstem.