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Decision-making is an important component in the perception–action coupling required for athletes to achieve fine performance. Signal detection theory (SDT) provides a means of quantifying athletes' decision-making processes, based on their ability to discriminate between different types of stimuli (sensitivity) and the locations of their response criteria along a decision axis in a given situation. Studies have shown differences in these two indices between athletes and less-experienced counterparts, although these studies were limited to unidimensional decision-making problems. In the present study, SDT analysis was applied to two-dimensional decision-making by volleyball players regarding their opponents' attacks, using a four-alternative forced-choice task combining judgments of the type (spike or tip) and direction (cross-court or down-the-line) of attacks. Furthermore, a temporal occlusion task was used to reveal the timecourses of changes in sensitivity and the location of response criteria relating to judgments of attack type and direction. There were three groups of participants, eight top-league players, ten collegiate players, and ten novices. The results showed clear effects of expertise and distinct timecourses for the two types of judgment. For the attack type judgments, the sensitivities of the top-league players were relatively low at the early occlusion points, and their response criteria were biased toward judging attacking actions as spikes. At the late occlusion points, their sensitivity peaked, and there was no bias in their response criteria. For the directional judgments, the sensitivity of the three groups improved as the occlusion point advanced, while their response criteria tended to become more similar, which was not the case for the attack type judgments. These results are discussed together with previous studies of volleyball players' decision-making and judgments regarding deceptive actions in sports. [ABSTRACT FROM AUTHOR]

Background: Advanced glycation end products (AGEs) are heterogeneous proinflammatory molecules produced by a non-enzymatic glycation reaction between reducing sugars (and their metabolites) and biomolecules with amino groups, such as proteins. Although increases in and the accumulation of AGEs have been implicated in the onset and exacerbation of lifestyle- or age-related diseases, including diabetes, their physiological functions have not yet been elucidated in detail. Methods and results: The present study investigated the cellular responses of the macrophage cell line RAW264.7 stimulated by glycolaldehyde-derived AGEs (Glycol-AGEs) known as representative toxic AGEs. The results obtained showed that Glycol-AGEs significantly promoted the proliferation of RAW264.7 cells at a low concentration range (1–10 µg/mL) in a concentration-dependent manner. On the other hand, neither TNF-α production nor cytotoxicity were induced by the same concentrations of Glycol-AGEs. The increases observed in cell proliferation by low concentrations of Glycol-AGEs were also detected in receptor triple knockout (RAGE-TLR4-TLR2 KO) cells as well as in wild-type cells. Increases in cell proliferation were not affected by various kinase inhibitors, including MAP kinase inhibitors, but were significantly suppressed by JAK2 and STAT5 inhibitors. In addition, the expression of some cell cycle-related genes was up-regulated by the stimulation with Glycol-AGEs. Conclusions: These results suggest a novel physiological role for AGEs in the promotion of cell proliferation via the JAK-STAT pathway. [ABSTRACT FROM AUTHOR]

Background: Methylglyoxal (MGO) is a known toxic byproduct of glycolysis, with MGO-induced cytotoxicity believed to contribute to the pathogenesis of several diseases. Glyoxalase I (GLO1) is a key enzyme for eliminating MGO in mammalian cells, therefore, compounds affecting GLO1 activity are potential therapeutic agents for MGO-induced disorders. Previously, we found nordihydroguaiaretic acid (NDGA) as a potent GLO1 inhibitor. Methods: The inhibitory characteristics of NDGA were determined spectrophotometrically with recombinant GLO1. NDGA-induced growth-inhibition and accumulation of MGO-derived advanced glycation end products (AGEs) were examined in EA.hy926 cells. Results: NDGA showed significant inhibition of GLO1 enzymatic activity in a dose-dependent manner. Its Ki value was estimated to be 146-fold lower than that of myricetin, a known GLO1 inhibitor. The co-addition of MGO with NDGA to the cells resulted in significant growth inhibition, suggesting that MGO accumulation, sufficient to affect cell growth, was caused by NDGA inhibiting GLO1. These findings were supported by the observations that the addition of aminoguanidine, a typical MGO scavenger, significantly reversed cell-growth inhibition by co-addition of MGO with NDGA, and that an increase in intracellular MGO-derived AGEs was observed during incubation with the co-addition of MGO with NDGA. Conclusion: NDGA was found to be a novel and potent inhibitor of GLO1. The co-addition of NDGA with MGO to the cells resulted in increased intracellular MGO accumulation followed by enhanced cell-growth inhibition. [ABSTRACT FROM AUTHOR]

Introduction: Past studies have provided evidence that the effects of tactile stimulation on binocular rivalry are mediated by primitive features (orientation and spatial frequency) common in vision and touch. In this study, we examined whether such effects on binocular rivalry can be obtained through the roughness of naturalistic objects. In three experiments, the total dominant time of visual percepts of two objects was measured under binocular rivalry when participants touched one of the objects. Result: In Experiment 1, the total dominant time for the image of artificial turf and bathmat was prolonged by congruent tactile stimulation and shortened by incongruent tactile stimulation. In Experiment 2, we used the same stimuli but rotated their visual images in opposite directions. The dominant time for either image was prolonged by congruent tactile stimulation. In Experiment 3, we used different types of stimuli, smooth marble and rough fabric, and noted significant effects of the congruent and incongruent tactile stimulation on the dominant time of visual percepts. Conclusion: These three experiments demonstrated that visuo-tactile interaction on binocular rivalry can be mediated by roughness. [ABSTRACT FROM AUTHOR]

Background: We previously reported that advanced glycation endproducts (AGEs) increase the proinflammatory activity of high mobility group box-1 (HMGB1), a representative damage-associated molecular pattern molecule (DAMP), through their direct interaction. This suggested that AGEs activate other DAMPs and led us to search for novel DAMPs capable of interacting with AGEs. Methods and results: The chromatographic analysis using AGE-immobilized gel revealed the ribosomal protein family to be a factor with binding activity to AGEs. Ribosomal protein L9 (RPL9), a member of the ribosomal protein family, was found in the centrifugal supernatant of ruptured cells and in the serum of lipopolysaccharide (LPS)-stimulated sepsis model mice, exhibiting similar characteristic properties to HMGB1. Although HMGB1 potentiated LPS-stimulated TNF-α expression in macrophage-like RAW264.7 cells, RPL9 hardly exhibited this activity. Of note, RPL9 significantly suppressed the potentiated mRNA expression and protein production of TNF-α by HMGB1 plus LPS stimulation, suggesting its regulatory roles in DAMP-induced proinflammatory activity. Based on the differential scanning fluorimetric analysis, the direct interaction between RPL9 and HMGB1 may play a role in the suppressive effects of RPL9. Conclusions: This study suggested that RPL9 is a novel type of DAMP with a regulatory role in the proinflammatory response and provided insight into the pathophysiology of inflammatory diseases. [ABSTRACT FROM AUTHOR]

Various biomarkers have been proposed for sepsis; however, only a few become the standard. We previously reported that plasma histidine-rich glycoprotein (HRG) levels decreased in septic mice, and supplemental infusion of HRG improved survival in mice model of sepsis. Moreover, our previous clinical study demonstrated that HRG levels in septic patients were lower than those in noninfective systemic inflammatory response syndrome patients, and it could be a biomarker for sepsis. In this study, we focused on septic patients and assessed the differences in HRG levels between the non-survivors and survivors. We studied ICU patients newly diagnosed with sepsis. Blood samples were collected within 24 h of ICU admission, and HRG levels were determined using an enzyme-linked immunosorbent assay. Ninety-nine septic patients from 11 institutes in Japan were included. HRG levels were significantly lower in non-survivors (n = 16) than in survivors (n = 83) (median, 15.1 [interquartile ranges, 12.7–16.6] vs. 30.6 [22.1–39.6] µg/ml; p < 0.01). Survival analysis revealed that HRG levels were associated with mortality (hazard ratio 0.79, p < 0.01), and the Harrell C-index (predictive power) for HRG was 0.90. These results suggested that HRG could be a novel prognostic biomarker for sepsis. [ABSTRACT FROM AUTHOR]

Previously, we found that advanced glycation endproducts (AGEs) directly interact with tumor necrosis factor (TNF)-like weak inducer of apoptosis, a cytokine that controls inflammation, and that this interaction inhibited its action. This finding raised the novel possibility that AGEs alter the function of other cytokines through direct interaction. To investigate this possibility, we performed comprehensive screening for candidates that interacted with AGEs using protein array analysis. The array analysis revealed that high mobility group box-1 (HMGB1) had a markedly high affinity for AGEs. HMGB1 is a representative proinflammatory damage-associated molecular pattern molecule, and is reported to interact with lipopolysaccharide (LPS) directly to exert its inflammatory function. When LPS, HMGB1, and AGEs were mixed, the mobility of HMGB1 had shifted significantly in native PAGE, suggesting that these three molecules formed a triplet complex. The addition of AGEs to the LPS–HMGB1 mixture synergistically potentiated LPS–HMGB1-stimulated TNF-α mRNA expression in macrophage-like RAW264.7 cells. In addition, using receptor knockout clones, the increased proinflammatory response by LPS–HMGB1–AGEs complex was demonstrated to be mediated via Toll-like receptor 4 and receptor for AGEs. Taken together, this study suggested that AGEs carry out their pathophysiological roles by potentiating the LPS–HMGB1-stimulated proinflammatory response through direct interactions. [ABSTRACT FROM AUTHOR]

This study investigated the effects of declined accommodation on reading performance in non-native and native languages. Eighteen native Japanese speakers participated: eight presbyopes and ten non-presbyopes. In the experiment, participants were asked to scan, or sequentially read six-word items presented in two-line texts, identify a non-word target as quickly as possible, and indicate its location. In addition to the participant type (presbyopes/non-presbyopes) and language of the reading material (Japanese/English), viewing distance (35 cm/70 cm) and contrast (18%/100%) were manipulated. The results showed that the presbyopes exhibited worse reading performance than the non-presbyopes at closer distances irrespective of the language. Notably, the inferiority of the presbyopes' reading performance was more pronounced when they read in a non-native language than in their native language. It should be noted that differences in reading performance between the presbyopes and non-presbyopes were subtle for high-contrast words at longer viewing distances, indicating that age- or cohort-related perceptual, motor, and cognitive differences were almost negligible, but accommodation mattered. These results suggest that the effect of accommodation decline is influenced by the language of the reading material. [ABSTRACT FROM AUTHOR]

There is ample evidence that motor learning changes the function of perceptual systems. Previous studies examining the interactions between speech production and perception have shown that the discrimination of phonetic contrasts characterized by the difference in articulatory place features is altered following their production changes caused by the perturbation of auditory feedback. The present study focused on a voiced–voiceless contrast in stop consonants, which is characterized by a temporal articulatory parameter, voice-onset time (VOT). In the experiment, we manipulated the participants' motor functions concerning VOT using a cross-categorical auditory feedback (CAF) paradigm (Mitsuya et al. in J Acoust Soc Am 135:2986–2994, 2014), in which a pre-recorded syllable sound starting with a voiced stop consonant (/da/) was fed back simultaneously with the participant's utterance of a voiceless stop consonant (/ta/), and vice versa. The VOT difference between /da/ and /ta/ productions was increased by the CAF, which is consistent with the result of Mitsuya's study. In addition, we conducted perceptual identification tasks of /da/-/ta/ continuum stimuli varying in VOT before and after the CAF task, and found that the identification function became sharper after as compared to before the CAF task. A significant positive correlation between such production and perception changes was also found. On the basis of these results, we consider that the change in motor function concerning VOT affected voiced–voiceless perceptual processing. The present study is the first to show the involvement of the speech production system in the perception of phonetic contrasts characterized by articulatory temporal features. [ABSTRACT FROM AUTHOR]

The detection of a silent interval or gap provides important insight into temporal processing by the auditory system. Previous research has uncovered a multitude of empirical findings leaving the mechanism of gap detection poorly understood and key issues unresolved. Here, we expand the findings by measuring psychometric functions for a number of conditions including both across-frequency and across-intensity gap detection as a first study of its kind. A model is presented which not only accounts for our findings in a quantitative manner, but also helps frame the body of work on auditory gap research. The model is based on the peripheral response and postulates that the identification of gap requires the detection of activity associated with silence. [ABSTRACT FROM AUTHOR]

Advanced glycation end products (AGEs) are formed from the non-enzymatic glycation reaction of reducing sugars or their metabolites with the free amino groups of several biomolecules and are known to play pathophysiological roles in various inflammatory diseases. In an earlier study, it was suggested that tumor necrosis factor-like weak inducer of apoptosis (TWEAK) has a unique role to regulate the tumor necrosis factor α (TNFα)-induced inflammatory response. In this study, we investigated the effect of the AGEs-TWEAK interaction on proinflammatory signaling responses in endothelial cells and the influence of AGEs on the cellular function of TWEAK in the inflammatory process. The effect of AGEs on the TWEAK/TNFα-induced gene expression of interleukin-8 (IL-8) was determined by real-time RT-PCR in endothelial-like EA.hy.926 cells. The pull-down assay was performed using recombinant His-tagged TWEAK and AGEs. The NF-κB activation was analyzed by Western blotting with canonical and non-canonical pathway-specific antibodies. AGEs dose-dependently inhibited TWEAK-induced IL-8 gene expression, whereas AGEs themselves had almost no effect on IL-8 expression. AGEs were found to bind directly to TWEAK in the pull-down assay. TNFα-induced IL-8 production and canonical NF-κB activation were suppressed by TWEAK pretreatment, whereas TWEAK-induced non-canonical NF-κB activation was enhanced by pretreatment. These effects induced by TWEAK pretreatment were abolished by the co-addition of AGEs. Our findings suggest that AGEs attenuate the function of TWEAK to regulate the TNFα-induced inflammatory responses, which provide important clues for understanding the significance of the AGEs-TWEAK interaction in inflammatory processes. [ABSTRACT FROM AUTHOR]

In the adult hypothalamus and ependymal lining of the third ventricle, tanycytes function as multipotential progenitor cells that enable continuous neurogenesis, suggesting that tanycytes may be able to mediate the restoration of homeostatic function after stroke. Voluntary wheel running has been shown to alter neurochemistry and neuronal function and to increase neurogenesis in rodents. In the present study, we found that voluntary exercise improved the survival rate and energy balance of stroke-prone spontaneously hypertensive rats (SHRSP/Kpo). We also investigated the effect of exercise on the proliferation and differentiation of hypothalamic cells using immunoreactivity for tanycytes and neural markers. The proliferation of elongated cells, which may be the tanycytes, was enhanced in exercising SHRSP compared to sedentary rats before and after stroke. In addition, the proliferation of cells was correlated with the induction of fibroblast growth factor-2 in the subependymal cells of the third ventricle and in the cerebrospinal fluid. Some of the newborn cells of exercising SHRSP showed differentiation into mature neurons after stroke. Our results suggest that voluntary exercise correlates with hypothalamic neurogenesis, leading to recovery of homeostatic functions in the adult brain after stroke. [ABSTRACT FROM AUTHOR]

To examine the tradeoff between manual reaction times (RTs) and smooth pursuit accuracy, we manipulated manual RTs to a visual target presented during pursuit by using a deadline procedure that required different response speeds to a target (300, 400, or 500 ms). Participants attempted to pursue a moving row of circles as accurately as possible, while responding to a target within a preset time. Stimulus velocity and target position were manipulated. As the preset time became shorter, participants responded with faster manual RTs and larger pursuit velocity errors, irrespective of the stimulus velocity, indicating a tradeoff between manual RTs and pursuit accuracy. Pursuit velocity errors were also larger after target onset. These results not only suggest that attentional resources as well as spatial shifts of attention play an important role in maintaining accurate pursuit, but also support the notion that a manual RT task is useful for revealing the operation of attention during pursuit. [ABSTRACT FROM AUTHOR]

Expertise in sports enhances the ability to anticipate forthcoming events from the observation of a player's actions. In the present study, we investigated whether this ability is applicable to deceptive action. In three experiments, performance at anticipating the direction change of a running opponent was examined with experienced rugby players and novice counterparts. These experiments were conducted with reaction-time and temporal-occlusion tasks, in combination with eye movement recordings and the presentation of filmed actions and their point-light representations. The main finding was that the experienced players were superior to the novices in their anticipation of deceptive actions, although their performance was still impaired by the deception, in comparison with their anticipation of nondeceptive actions. We also found that the experienced players anticipated nondeceptive actions less accurately than the novices, suggesting that the players' expectations of deceptive actions worked negatively on their judgments of nondeceptive actions. The results obtained with the point-light representations closely resembled those obtained with the filmed sequences, indicating that anticipation was based on the kinematics of the running action. These results are discussed in the context of recent developments in research on expertise and deception in sports. [ABSTRACT FROM AUTHOR]

The present study investigated the effects of presbyopia on the reading ability of middle-aged adults in a Japanese reading context, using the rapid serial visual presentation paradigm. Japanese words, each consisting of three characters, were sequentially presented at the same location on a display screen. Participants were instructed to read the words aloud as accurately as possible, irrespective of their order within the sequence. Experiment 1 showed that the reading performance for the presbyopes was far worse for the near-viewing (35 cm) than for the far-viewing (70 cm) conditions when the words were presented at 0.4° in character size. Experiment 2 investigated in detail the effect of luminance contrast on reading at a viewing distance of 35 cm. The minimums of the exposure durations within which the participants could read the words above 89.9 % correct (minimum exposure duration) were 498 ms/word for the presbyopes and 134 ms/word for the nonpresbyopes, both of which values were obtained at 100 % contrast. The critical contrast-that is, the contrast that doubled the minimum exposure duration that had been obtained at 100 % contrast-was considerably higher for the presbyopes (39.2 %) than for the nonpresbyopes (16.4 %). However, the reading performance for the presbyopes was improved more than threefold when the contrast was increased to 100 % in both experiments. Thus, our results provide psychophysical evidence for the dependency of presbyopes' reading on viewing distance and luminance contrast. [ABSTRACT FROM AUTHOR]

Post-ischemic inflammation is an essential step in the progression of brain ischemia-reperfusion injury. However, the mechanism that activates infiltrating macrophages in the ischemic brain remains to be clarified. Here we demonstrate that peroxiredoxin (Prx) family proteins released extracellularly from necrotic brain cells induce expression of inflammatory cytokines including interleukin-23 in macrophages through activation of Toll-like receptor 2 (TLR2) and TLR4, thereby promoting neural cell death, even though intracellular Prxs have been shown to be neuroprotective. The extracellular release of Prxs in the ischemic core occurred 12 h after stroke onset, and neutralization of extracellular Prxs with antibodies suppressed inflammatory cytokine expression and infarct volume growth. In contrast, high mobility group box 1 (HMGB1), a well-known damage-associated molecular pattern molecule, was released before Prx and had a limited role in post-ischemic macrophage activation. We thus propose that extracellular Prxs are previously unknown danger signals in the ischemic brain and that its blocking agents are potent neuroprotective tools. [ABSTRACT FROM AUTHOR]

To examine the spatial shift of attention during smooth pursuit, we measured reaction times (RTs) to a visual target that appeared during pursuit. Participants pursued a moving row of circular frames and responded to a target presented within one of the frames. The results showed large RT differences between stimulus velocities up to 5º/s and 10º/s or above. RTs were faster for a target appearing in the pursuit direction than for one in the opposite direction. When an auditory precue was presented, the RTs during pursuit at 10º/s were faster with increases in the stimulus onset asynchrony (SOA) between the cue and the target. Furthermore, RTs were faster in the cued than in the uncued direction. These results not only support the idea that RTs during pursuit reflect the operation of attention, but also suggest that attention during pursuit can be shifted by the abrupt onset of a target stimulus and/or by prior information regarding the onset of a target stimulus. [ABSTRACT FROM AUTHOR]

Vascular smooth muscle cell (SMC) hyperplasia is known to be an important component in the pathogenesis of arteriosclerosis and restenosis. Although heparin has been well recognized as the representative molecule suppressing SMC growth in vitro, attempts to use heparin as a therapeutic anti-restenosis drug have not favorably influenced the angiographic or clinical outcome after angioplasty in some clinical trials. In this study, we have examined the effect of histidine-rich glycoprotein (HRG), a relatively abundant serum glycoprotein (~100 μg/ml in human serum), on the growth inhibition of cultured vascular SMC by heparin. Vascular SMC growth was significantly inhibited by heparin, giving nearly 85% inhibition with 100 μg/ml heparin. HRG reversed heparin-induced SMC growth inhibition in a dose dependent manner; 75% restoration of cell growth was observed when 100 μg/ml of HRG was co-added with 100 μg/ml heparin. Interestingly, micromolar concentrations of the zinc ion (0–10 μM), compatible with concentrations released from activated platelets, were found to enhance the restorative action of HRG. Western blot experiment demonstrated no significant amounts of the HRG moiety in fetal bovine serum, eliminating the possible contribution of contaminant HRG from culture media. These findings indicate that HRG, in combination with the zinc ion, plays a role in modulating the SMC growth response in pathophysiological states and explain the lack of success of heparin as a therapeutic anti-restenosis drug in clinical trials. [ABSTRACT FROM AUTHOR]

IL-18 (0–100 ng/ml) specifically upregulated ICAM-1 expression on monocytes in human PBMC as demonstrated in our previous study. In the present study, we examined whether the synergistic upregulation of ICAM-1 occurred after the stimulation with the combination of IL-18 and IL-12 and whether the synergistic production of IFN-γ was dependent on the interaction between ICAM-1 on monocytes and LFA-1 on NK/T cells. The effect of IL-12 on ICAM-1 expression on monocytes was marginal even at the highest concentration (100 ng/ml). However, in the presence of IL-12 (100 ng/ml), the expression of ICAM-1 induced by IL-18 was significantly enhanced as compared with that obtained by IL-18 alone. In addition to the expression of ICAM-1 on monocytes, IFN-γ production was synergistically stimulated by IL-18 and IL-12. Anti-ICAM-1 and anti-LFA-1 Abs exhibited significant inhibitory effect on enhanced production of IFN-γ by the combination of two cytokines, in particular, anti-ICAM-1 showing the complete inhibition. These results as a whole indicated that synergistic effect of IL-18 and IL-12 on IFN-γ production in human PBMC is ascribed to the synergism of the effect of two cytokines on ICAM-1 expression on monocytes and that the subsequent ICAM-1/LFA-1 interaction plays an important role in the enhanced production of IFN-γ. [ABSTRACT FROM AUTHOR]

Developmental changes in the distribution of brain-specific chondroitin sulfate proteoglycans, neurocan and phosphacan/RPTPζ/β, in the hippocampus of the Sprague-Dawley rat were examined using monoclonal antibodies 1G2 and 6B4. The 1G2 immunoreactivity was predominant in the neonatal hippocampus while the 6B4 immunoreactivity was predominant in the mature hippocampus. Moderate 1G2 immunoreactivity was detected in the dentate gyrus and subiculum immediately after birth. Immunoreactivity reached a peak on postnatal days 7–10 (P7–P10) when intense 1G2 labeling was present throughout the neuropil layers of the hippocampus except the mossy fiber tract. 6B4 immunoreactivity was limited in the stratum lacunosum moleculare of CA1 in the neonatal hippocampus. It gradually increased by P21 when diffuse 6B4 immunoreactivity was detected in the stratum oriens and radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of the dentate gyrus, while 1G2 immunoreactivity decreased after P21. In the adult hippocampus, moderate 6B4 immunoreactivity was present in the stratum oriens and radiatum of Ammon's horn, and in the hilus and inner one-third molecular layer of the dentate gyrus, but not in the mossy fiber tract. In addition, strong 6B4 labeling appeared around a subset of neurons after P21. The results suggest that neurocan may have a role in the development of neuronal organization, while phosphacan/RPTPζ/β may contribute to the maintenance and plasticity of synaptic structure and function. Furthermore, the absence of 1G2 and 6B4 immunoreactivities in the stratum lucidum suggests that neurocan and phosphacan/RPTPζ/β may function as a barrier for the extension of mossy fibers and provide an environment permissive for fasciculation of the mossy fibers. [ABSTRACT FROM AUTHOR]

Severe nausea and vomiting are common side effects of anti-cancer chemotherapy. 5-HT3 receptor antagonists have been used for the treatment of these gastrointestinal symptoms. The purpose of this study was to examine whether specific changes in serotonin dynamics occurred in the gastrointestinal tract in mice in which Colon-26 adenocarcinoma cells were injected s.c., especially after treatment with cisplatin. The serotonin content of the small intestine of mice inoculated s.c. with Colon-26 adenocarcinoma increased significantly 2 weeks after the inoculation of the tumor cells; this was associated with an increase in tryptophan hydroxylase activity and the number of enterochromaffin cells as compared with control mice. Intravenous injection of cisplatin significantly reduced the serotonin content in the small intestine of Colon-26 tumour-bearing mice but not in control mice. The spontaneous release of serotonin from isolated intestine was not different between Colon-26 tumour-bearing and control mice; however, pretreatment of mice with cisplatin induced two fold increases in serotonin release from duodenum, jejunum and ileum in Colon-26 tumour-bearing mice but not in control mice. These results indicate that a region-specific increase in the number of enterochromaffin cells is observed in the intestine of Colon-26 tumour-bearing mice, associated with an increase in the serotonin content and tryptophan hydroxylase activity. Cisplatin treatment induced the release of serotonin from affected enterochromaffin cells in the gastrointestinal tract, which may be related to the occurrence of nausea in clinical use. [ABSTRACT FROM AUTHOR]

Abstract The traditional paradigm For studying the magical number is questioned and a new approach is sought in order to obtain a better conceptual understanding of this phenomenon. Building on earlier work, a theory is proposed whereby the results of an absolute identification experiment can be characterized by a single parameter to a reasonable approximation. This parameter is the variance in the subject's response to a sensory input. By reducing the magical number to a single parameter, we see that the value of the upper limit in information transmission depends not so much on the absolute magnitude of the response error, but actually on how Fast this error grows with range. The theory also predicts a little known characteristic of the magical number. If this prediction can be demonstrated experimentally, we shall need to reinterpret the magical number. [ABSTRACT FROM AUTHOR]

As one of the most lethal stroke subtypes, intracerebral hemorrhage (ICH) is acknowledged as a serious clinical problem lacking effective treatment. Available evidence from preclinical and clinical studies suggests that inflammatory mechanisms are involved in the progression of ICH-induced secondary brain injury. High mobility group box-1 (HMGB1) is a ubiquitous and abundant nonhistone DNA-binding protein, and is also an important proinflammatory molecule once released into the extracellular space from the nuclei. Here, we show that treatment with neutralizing anti-HMGB1 mAb (1 mg/kg, i.v. twice) remarkably ameliorated ICH-injury induced by local injection of collagenase IV in the striatum of rats. Administration of anti-HMGB1 mAb inhibited the release of HMGB1 into the extracellular space in the peri-hematomal region, reduced serum HMGB1 levels and decreased brain edema by protecting blood-brain barrier integrity, in association with decreased activated microglia and the expression of inflammation-related factors at 24 h after ICH. Consequently, anti-HMGB1 mAb reduced the oxidative stress and improved the behavioral performance of rats. These results strongly indicate that HMGB1 plays a critical role in the development of ICH-induced secondary injury through the amplification of plural inflammatory responses. Intravenous injection of neutralizing anti-HMGB1 mAb has potential as a novel therapeutic strategy for ICH. [ABSTRACT FROM AUTHOR]

Although delayed cerebral vasospasm (DCV) following subarachnoid hemorrhage (SAH) is closely related to the progression of brain damage, little is known about the molecular mechanism underlying its development. High mobility group box-1 (HMGB1) plays an important role as an initial inflammatory mediator in SAH. In this study, an SAH rat model was employed to evaluate the effects of anti-HMGB1 monoclonal antibody (mAb) on DCV after SAH. A vasoconstriction of the basilar artery (BA) associated with a reduction of nuclear HMGB1 and its translocation in vascular smooth muscle cells were observed in SAH rats, and anti-HMGB1 mAb administration significantly suppressed these effects. Up-regulations of inflammation-related molecules and vasoconstriction-mediating receptors in the BA of SAH rats were inhibited by anti-HMGB1 mAb treatment. Anti-HMGB1 mAb attenuated the enhanced vasocontractile response to thrombin of the isolated BA from SAH rats and prevented activation of cerebrocortical microglia. Moreover, locomotor activity and weight loss recovery were also enhanced by anti-HMGB1 mAb administration. The vasocontractile response of the BA under SAH may be induced by events that are downstream of responses to HMGB1-induced inflammation and inhibited by anti-HMGB1 mAb. Anti-HMGB1 mAb treatment may provide a novel therapeutic strategy for DCV and early brain injury after SAH. [ABSTRACT FROM AUTHOR]