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PubMed2003

The acquisition, retention and reversal of spatial learning in the morris water maze task following withdrawal from an escalating dosage schedule of amphetamine in wistar rats.

Two experiments were carried out to evaluate the effects of amphetamine withdrawal in rats on spatial learning in the water maze. A schedule of repeated d-amphetamine administration lasting for 6 days, with three injections per day (1-5 mg/kg, i.p.), was employed. Experiment 1 demonstrated that amphetamine withdrawal did not impair the acquisition of the water maze task (third to fourth withdrawal days), but amphetamine-withdrawn rats made more target-zone visits and reached the former location of the platform quicker than controls during the probe test (fifth withdrawal day). In experiment 2, retention of the location of the escape platform was assessed in animals having been pre-trained on the water maze task before treatment. On the third withdrawal day, retention of the former platform location was assessed in a probe test. Retention was only clearly seen in the measure of target zone visits, and performance did not differ between groups. Next, the animals were trained to escape to a new location in the water maze on withdrawal days 4-5. A reversal effect could be discerned across the first four trials, as evident by the animals' tendency to search in the former target quadrant. This interfered with the new learning, but amphetamine-withdrawn animals appeared to overcome it more rapidly than saline-treated controls. This finding is consistent with the view that amphetamine withdrawal can enhance behavioural switching, which could be expressed as a reduction of proactive interference during learning; and, it is in line with our previous finding that latent inhibition is also attenuated during amphetamine withdrawal.

Amphetamine↗
PubMed1999

The neural substrate and temporal dynamics of interference effects in working memory as revealed by event-related functional MRI.

Research on the prefrontal cortex (PFC) of monkeys and humans indicates that this region supports a heterogeneous repertoire of mental processes that contribute to many complex behaviors, such as working memory. Anatomical evidence for some of these processes derives from functional neuroimaging experiments using blocked experimental designs, which average signal across all components of many trials and therefore cannot dissociate distinct processes with different time courses. Using event-related functional MRI, we were able to isolate temporally the neural correlates of processes contributing to the target presentation, delay, and probe portions of an item-recognition task. Two types of trials were of greatest interest: those with Recent Negative probes that matched an item from the target set of the previous, but not the present, two trials, and those with Nonrecent Negative probes that did not match a target item from either the present or the two previous trials. There was no difference between the two trial types in target presentation (i.e., encoding) or delay-period (i.e., active maintenance) PFC activation, but there was significantly greater activation for Recent Negatives than Nonrecent Negative activation associated with the probe period within left ventrolateral PFC. These findings characterize spatially and temporally a proactive interference effect that may reflect the operation of a PFC-mediated response-inhibition mechanism that contributes to working memory performance.

Adult↗
PubMed1991

Long-lasting depression of the factor XII-dependent fibrinolytic system in patients with myocardial infarction undergoing thrombolytic therapy with recombinant tissue-type plasminogen activator: a randomized placebo-controlled study.

In a randomized placebo-controlled study, seven patients with acute myocardial infarction allocated to intravenous treatment with 100 mg of recombinant tissue-type plasminogen activator (rt-PA) and seven patients allocated to placebo were studied during eight sampling periods before and after treatment. Seven patients with acute myocardial infarction treated intravenously with 1.5 million U of streptokinase were later studied during two sampling periods before and after treatment. The placebo group showed no significant deviations of endogenous factor XII-dependent fibrinolytic activity (p greater than 0.05). In the rt-PA group, this activity decreased significantly (p less than 0.001) after the infusion and remained depressed throughout the 1st 4 days. A significant decrease in activity (p less than 0.05) was also found in the streptokinase-treated patients. The depletion of factor XII-dependent fibrinolytic activity was not due to generation of inhibition or a depletion of factor XII, prekallikrein and plasminogen, but could be related to the proactivator of this system. It is concluded that rt-PA (and streptokinase) treatment in patients with acute myocardial infarction causes a prolonged depletion of factor XII-dependent fibrinolytic activity. This depression of endogenous fibrinolytic activity needs to be evaluated in relation to the enhanced risk of coronary reocclusion after thrombolytic therapy.

Depression, Chemical↗
PubMed2005

TGF-beta antisense oligonucleotides reduce mRNA expression of matrix metalloproteinases in cultured wound-healing-related cells.

The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix. The transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. We investigated the effect of TGF-beta antisense oligonucleotides on the mRNA expression of matrix metalloproteinases in cultured human keratinocytes, fibroblasts and endothelial cells using multiplex RT-PCR. The treatment of keratinocytes and fibroblasts with TGF-beta antisense oligonucleotides resulted in a significant decrease of expression of mRNA of MMP-1 and MMP-9 compared to controls. Accordingly, a decreased expression of MMP-1 mRNA in endothelial cells was detectable. Other MMPs were not affected. Affecting all dermal wound-healing-related cell types, TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction in chronic wounds. Pharmaceutical intervention in this area ultimately may help clinicians to proactively intervene in an effort to prevent normal wounds from becoming chronic.

Cell Line↗
PubMed1975

Alternate complement pathway induction of aggregation and release of 5-hydroxytryptamine and adenosine diphosphate by rabbit platelets.

The present studies investigated patterns of rabbit platelet aggregation and release of 5-hydroxytryptamine (5HT) utilizing nine variables: three different types of challenge, soluble antigen and antibody (AG-AB), zymosan (Z), an agent known to activate the alternate complement pathway (ACP), and Z preincubated in lightly heparinized plasma so as to become coated with complement (ZC); three different types of platelet-rich plasma (PRP), lightly heparinized PRP in which both complement pathways are active, ethylene glycol tetraacetic acid-PRP (EGTA-PRP) in which only the ACP is active, and ethylene diamine tetraacetic acid PRP (EDTA-PRP), which inhibits both complement pathways; three different types of inhibitors, cobra venom factor (CoF), which causes activation of C3 proactivator (C3PA) to C3 activator (C3A) and fluid phase decomplementation of C3 and C5 through C9, adenosine monophosphate (AMP), a specific antagonist of ADP, and tosyl arginine methyl ester (TAME), an inhibitor thought to act not only on the first component of complement, but also on a platelet membrane site of mediating complement-induced platelet injury as well as on C3PAse. In heparinized PRP, both AG-AB and Z produced biphasic aggregation and prompt and extensive 5HT release. A brief lag period noted with both AG-AB and Z challenge was not observed with ZC challenge, indicating that this lag period represented time required for generation of the necessary complement-dependent membrane-injuring activity. Prior decomplementation by CoF entirely prevented both aggregation and release by either AG-AB or Z but by ZC, indicating first that fluid-phase ACP activation did not produce platelet injury, and second that ZC had on its surface an activity capable of producing immediate biphasic aggregation and prompt 5HT release without the further participation of later acting complement components. Both AMP and TAME eliminated the second phase of aggregation and diminished or eliminated 5HT release with all three challenges, suggesting that both inhibitors might be operative on similar or identical platelet membrane receptors mediating complement-dependent platelet injury. In EGTA-PRP, AG-AB and Z produced delayed monophasic aggregation and delayed and diminished 5HT release, whereas ZC produced immediate although monophasic aggregation but delayed and diminished 5HT release. This suggested that all three challenges were capable of producing ACP-mediated platelet injury.

Adenosine Diphosphate↗
PubMed1985

Short-term memory for simultaneously presented visual and auditory signals in the pigeon.

A series of divided-attention experiments in which matching to the visual or auditory component of a tone-light compound was compared with matching to visual or auditory elements as sample stimuli were carried out. In 0-s delayed and simultaneous matching procedures, pigeons were able to match visual signals equally well when presented alone or with a tone; tones were matched at a substantially lower level of accuracy when presented with light signals than when presented as elements. In further experiments, it was demonstrated that the interfering effect of a signal light on tone matching was not related to the signaling value of the light, and that the prior presentation of light proactively interfered with auditory delayed matching. These findings indicate a divided attention process in which auditory processing is strongly inhibited in the presence of visual signals.

Animals↗
PubMed1993

Context, time, and memory retrieval in the interference paradigms of Pavlovian learning.

In this article I review research and theory on the "interference paradigms" in Pavlovian learning. In these situations (e.g., extinction, counterconditioning, and latent inhibition), a conditioned stimulus (CS) is associated with different unconditioned stimuli (USs) or outcomes in different phases of the experiment; retroactive interference, proactive interference, or both are often observed. In all of the paradigms, contextual stimuli influence performance, and when information is available, so does the passage of time. Memories of both phases are retained, and performance may depend on which is retrieved. Despite the similarity of the paradigms, conditioning theories tend to explain them with separate mechanisms. They also do not provide an adequate account of the context's role, fail to predict the effects of time, and overemphasize the role of learning or storage deficits. By accepting 4 propositions about animal memory (i.e., contextual stimuli guide retrieval, time is a context, different memories are differentially dependent on context, and interference occurs at performance output), a memory retrieval framework can provide an integrated account of context, time, and performance in the various paradigms.

Animals↗
PubMedDate not supplied

An in-depth analysis of lead effects in a delayed spatial alternation task: assessment of mnemonic effects, side bias, and proactive interference.

This study examined the effects of chronic postweaning lead (Pb) exposure in Long-Evans rats on a series of spatial alternation tasks. All tasks were administered in automated testing chambers, with a nosepoke as the critical response. While neither Pb-exposed group (median blood lead levels: 19 and 39 micrograms/dl, respectively) was impaired in learning the alternation rule, both groups performed more poorly than controls on the alternation task with variable intertrial delays (0, 10, 20, and 40 s). The deficit was constant across delays, arguing against memory dysfunction. Analyses of the responses on individual trials shed further light on the impaired and spared processes in the Pb-exposed rats. First, these analyses revealed stronger side biases in the higher exposure group. One interpretation is that these animals experienced impatience when the longer delays were included, making it more difficult for them to inhibit a prepotent response to a preferred side. In contrast, these trial-by-trial analyses revealed that several other factors-retention interval, semantic proactive interference, and temporal discriminability-exerted similar effects on performance in the control and lead-exposed animals. The use of logistic regression for these trial-by-trial analyses provided a means of simultaneously assessing the influence of several variables on performance, a significant advantage when there is confounding or interactions between variables.

Animals↗
PubMed2005

Aggression, social cognitions, anger and sadness in bullies and victims.

BACKGROUND: The present study aimed to investigate children's social information processing (SIP) and emotions in the bullying situation, taking into account reactive and proactive aggression. More specifically, we investigated the way in which children interpret social information, which goals they select, how they evaluate their responses and which emotions they express in hypothetical situations. METHOD: The participants comprised 242 Dutch children (120 girls and 122 boys; mean age: 117.2 months), who were assigned by means of peer nominations (Salmivalli, Lagerspetz, et al., 1996) to one of the following roles: bully (n=21), follower of the bully (n=38), victim (n=35), defender of the victim (n=48), outsider (n=52) and not involved (n=32). Sixteen children (including 3 bully/victims) were not given any role. The reactive and proactive aggression scale (Dodge, & Coie, 1987) was filled out by teachers in order to test the association between these types of aggression and involvement in bullying. Children were presented with ambiguous scenarios and responded to questions about attribution of intent, goal selection and emotions (anger and sadness). In addition, two questionnaires were administered to children: one assessed perceived self-efficacy in performing aggression, inhibiting aggression and using verbal persuasion skills, and the other assessed expected outcomes from behaving aggressively or prosocially. RESULTS: Results showed that while reactive aggression was common in bullies and victims, proactive aggression was only characteristic of bullies. Both bullies and victims, compared to the other children, scored higher on hostile interpretation, anger, retaliation and ease of aggression. Bullies and followers claimed that it was easy for them to use verbal persuasion, while victims turned out to be the saddest group. All children, irrespective of their role in the peer group, thought that aggressive as well as prosocial behavior was more likely to produce desired results from a friendly peer than from an aggressive one. CONCLUSIONS: Bullies and victims seem to be similar in reactive aggression, SIP, and in the expression of anger, but the motivations which lead to their behavior may be different, as well as the final outcomes of their acts.

Aggression↗
PubMed1990

The haemostatic balance in groups of thrombosis-prone patients. With particular reference to fibrinolysis in patients with myocardial infarction.

The concept of the haemostatic balance was reviewed, and its potential role in the regulation of tissue repair and the pathogenesis of thrombotic processes was surveyed. Physiological activation of coagulation appears to be dominated by effects of degenerated and injured cells of the vascular wall causing local release of thromboplastin and exposition of activating surfaces. Inhibition of coagulation impairs its progression and the non-thrombogenic nature of the normal endothelium is chiefly caused by the binding of inhibitory components (antithrombin-III, protein C) to specific receptor sites. Physiological activation of fibrinolysis appears to be triggered by and limited to the fibrin because of a specific affinity to fibrin of plasminogen and plasminogen activators. Systemic activation of fibrinolysis is prevented by primary (alpha 2-antiplasmin) and secondary (alpha 2-macroglobulin, alpha 1-antitrypsin) plasmin inhibitors. A plasminogen binding protein (histidine-rich glycoprotein), plasmin inhibitors and activator inhibitors appear to contribute to the regulation of the initial phase of fibrinolysis. A deviation from normal of the dynamic balance, regulating fibrin formation and resolution, may lead to a haemorrhagic and/or a thrombophilic state. Described were the optimization of selected methods for assessment of variables involved in the haemostatic balance. An overestimation of plasminogen concentrations in plasma may occur in patients with elevated levels of fibrinogen or fibrin degradation products, when using assays based on the activation of plasminogen by streptokinase followed by the hydrolysis of a synthetic chromogenic substrate. This source of error could be eliminated by presence of fibrinogen in excess in the plasminogen assay, thereby securing maximum stimulation of the plasminogen-streptokinase complex. The presence of cryoglobulin in plasma interferes with the assessment in euglobulins of plasminogen activator activities. Experiments indicate that tissue-type plasminogen activator adsorb cryoglobulins and that a cold-promoted activation of the factor XII-dependent proactivator system of fibrinolysis is related to the presence of cryoglobulins. Experiments supported the existence of an as yet not characterized factor XII-dependent proactivator. Strictly optimized procedures for the preparation of euglobulins for the accurate determination of plasminogen activators were recommended. The determination of plasminogen activator inhibition in plasma was optimized and simplified. The amidolytic assay of antithrombin-III was shown to be influenced by adsorption to laboratory utensils and aggregation of thrombin. This error could be corrected by protection with additives (Tween 80, polyethyleneglycol 6,000), which also improved the solubility of the chromogenic substrates in aqueous media. The role of thrombosis in myocardial infarction was reviewed.(ABSTRACT TRUNCATED AT 400 WORDS)

Antithrombin III↗
PubMed2005

Glucocorticoid interaction with aggression in non-mammalian vertebrates: reciprocal action.

Socially aggressive interaction is stressful, and as such, glucocorticoids are typically secreted during aggressive interaction in a variety of vertebrates, which may both potentiate and inhibit aggression. The behavioral relationship between corticosterone and/or cortisol in non-mammalian (as well as mammalian) vertebrates is dependent on timing, magnitude, context, and coordination of physiological and behavioral responses. Chronically elevated plasma glucocorticoids reliably inhibit aggressive behavior, consistent with an evolutionarily adaptive behavioral strategy among subordinate and submissive individuals. Acute elevation of plasma glucocorticoids may either promote an actively aggressive response via action in specialized local regions of the brain such as the anterior hypothalamus, or is permissive to escalated aggression and/or activity. Although the permissive effect of glucocorticoids on aggression does not suggest an active role for the hormone, the corticosteroids may be necessary for full expression of aggressive behavior, as in the lizard Anolis carolinensis. These effects suggest that short-term stress may generally be best counteracted by an actively aggressive response, at least for socially dominant proactive individuals. An acute and active response may be evolutionarily maladaptive under chronic, uncontrollable and unpredictable circumstances. It appears that subordinate reactive individuals often produce compulsorily chronic responses that inhibit aggression and promote submissive behavior.

Aggression↗
PubMed1976

Studies on the properties of a streptococcal preparation OK-432 (NSC-B116209) as an immunopotentiator. I. Activation of serum complement components and peritoneal exudate cells by group A streptococcus.

The inhibition of transplanted tumors in animals, which were previously injected with a streptococcal preparation, OK-432, has been suggestible to be induced by direct or host mediated effects. In this paper, it was examined of immunopotentiating ability of Group A streptococcus (Su-strain), which is a active component of OK-432, with respects to reticuloendotherial system and serum complement components. Human fresh serum incubated with the heated streptococcus (HSu-coccus) was analyzed by means of immunoelectrophoresis. Activated component of C3 proactivator was observed in gamma region as immunoprecipitin line developed by rabbit anti human C3 proactivator serum, and conversion of C3 component (beta1C) to beta1A was observed in alpha region by rabbit anti human beta1C/beta1A serum. The activation of serum complement components might be occurred via alternate pathway, because EDTA inhibited the activation but EGTA did not. Meanwhile, the peritoneal exudate cells from mice injected intraperitoneally with HSu-coccus were examined with respects to cell population and their antitumor effect. On the 7th day after injection of HSu-coccus, about 90% of the peritoneal cells was lymphocytes, and 70% of these lymphocytes was susceptible to rabbit anti mouse thymus cell serum or to AKR anti thetaC3H serum. When L1210 leukemia cells preincubated with these peritoneal cells were inoculated intraperitoneally into BALB/c mice, the leukemic cells could not allowed the growth, resulting in prolongation of life-span of the experimental animals. These results suggested that nonspecific effector activity of T-derived lymphocyte induced by HSu-coccus could be one of the factors participating in antitumor activity of OK-432. Additionally, the results obtained with OK-432 were most the same as those with HSu-coccus in these respects. Further, the relation between the stimulation of leucocytes and activation of complement components was discussed.

Animals↗
PubMed2001

Proactive interference, accessibility bias, and process dissociations: valid subjective reports of memory.

Proactive interference was assessed with a variant of the process-dissociation procedure, which separates effects of habit (accessibility bias) and recollection (discriminability). In three cued-recall experiments, proactive interference was shown to be an effect of bias rather than an effect on actual remembering. Divided attention, age, and study duration selectively influenced the recollection parameter, whereas training probability selectively influenced the habit parameter. Furthermore, in Experiments 2 and 3, subjective reports of remembering were highly correlated with, and nearly identical to, objective estimates of recollection gained from the process-dissociation procedure. The authors discuss the relevance of the results to theories of proactive interference and argue that older adults' greater susceptibility to interference effects is sometimes caused by an inability to recollect rather than by an inability to inhibit a preponderant response.

Adult↗
PubMed2004

Targeting TGF-beta in human keratinocytes and its potential role in wound healing.

The pathology of chronic dermal ulcers is characterized by excessive proteolytic activity which degrades extracellular matrix (required for cell migration) and growth factors and their receptors. The transforming growth factor-beta (TGF-beta) has been identified as an important component of wound healing. Recent developments in molecular therapy offer exciting prospects for the modulation of wound healing, specifically those targeting TGF-beta. We investigated expression of angiogenic bFGF and VEGF, and collagenases MMP-2 and MMP-9 in tissue samples from chronic dermal wounds by immunohistochemistry. The effect of TGF-beta targeting using antisense oligonucleotides on the expression of these factors was analysed by ELISA in human keratinocytes. Immunohistochemical investigation demonstrated a decreased expression of bFGF and VEGF protein, and an increased expression of MMP-2 and MMP-9 in tissue samples from chronic dermal wounds compared to normal human skin. Antisense TGF-beta oligonucleotide treatment down-regulated collagenase secretion activity and up-regulated VEGF secretion in vitro. Therefore, TGF-beta antisense oligonucleotide technology may be a potential therapeutic option for the inhibition of proteolytic tissue destruction, and stimulation of angiogenesis in chronic wounds. Improving basic knowledge and pharmaceutical intervention in this area ultimately may help clinicians to identify and proactively intervene in an effort to prevent normal wounds from becoming chronic.

Cell Line↗