Breast cancer micrometastases: Different interactions of carcinoma cells with normal and cancer patients' bone marrow stromata

The apparently dormant breast cancer micrometastases in haemopoietic marrow are correlated with distant metastatic carcinoma dissemination. We studied in vitro interactions of carcinoma cells with adjacent stromata, using connective tissue cell cultures from breast and bone marrow samples of normal donors, comparing them to the pericancerous breast tissue and bone marrows of 12 selected patients with invasive breast carcinomas. Cancer cells were detected by immunocytochemistry and RT-PCR in all the bone marrows and in most blood samples of the studied patients. We monitored the growth and interaction of carcinoma MCF-7 cells with the stromata. The normal breast stroma sustained typical massive cancer growth. The pericancerous breast stroma induced the invasive mesenchymal pattern of growth. Normal bone marrow stroma induced the same conversion and was highly adhesive, retaining the cells in the stroma, but carcinoma patients' bone marrow stromata underwent low adhesive interactions with cancer cells, releasing them potentially into the circulation. The semi-quantitative RT-PCR indicated an enhanced expression of the hepatocyte growth factor and its receptor c-met in breast and bone marrow stromata of cancer patients. The input of cancer cells into the normal bone marrow may induce modifications of the local microenvironment, favourable for growth and release of carcinoma cells into the systemic circulation, which correlate with the poor prognosis of patients with bone marrow micrometastases. This revised version was published online in July 2006 with corrections to the Cover Date.     

Glutamate receptor antagonism in inferior colliculus attenuates elevated startle response of high anxiety diazepam-withdrawn rats

Rats segregated according to low (LA) or high (HA) anxiety levels have been used as an important tool in the study of fear and anxiety. Since the efficacy of an anxiolytic compound is a function of the animal's basal anxiety level, it is possible that chronic treatment with a benzodiazepine (Bzp) affects LA and HA animals differently. Based on these assumptions, this study aimed to provide some additional information on the influence of acute, chronic (18 days) and withdrawal effects (48 h) from diazepam (10 mg/kg), in rats with LA or HA levels, on startle response amplitude. For this purpose, the elevated plus-maze (EPM) test was used. In addition, the role of glutamate receptors of the central nucleus of the inferior colliculus (cIC), the most important mesencephalic tectum integrative structure of the auditory pathways and a brain region that is linked to the processing of auditory information of aversive nature, was also evaluated. Our results showed that, contrary to the results obtained in LA rats, long-term treatment with diazepam promoted anxiolytic and aversive effects in HA animals that were tested under chronic effects or withdrawal from this drug, respectively. In addition, since Bzp withdrawal may function as an unconditioned stressor, the negative affective states observed in HA rats could be a by-product of GABA-glutamate imbalance in brain systems that modulate unconditioned fear and anxiety behaviors, since the blockade of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) and N-methyl-d-aspartate (NMDA) glutamate receptors in the cIC clearly reduced the aversion promoted by diazepam withdrawal.     

Watching where you look: modulation of visual processing of foveal stimuli by spatial attention

Two experiments investigated the effect of sustained selective spatial attention upon the perceptual analysis of stimuli within the center of gaze. Spatial attention has typically been studied in relation to peripheral stimuli, and its relevance to the processing of central stimuli has remained relatively ignored. Here, behavioral measures in normal human volunteer participants showed that focused spatial attention can also influence responses to central stimuli, over and beyond the advantage conferred by their foveation. Event-related potentials (ERPs) showed that the action of attention upon foveal stimuli included the modulation of perceptual processing in extrastriate visual areas. Surprisingly, the visual modulation revealed an intriguing and consistent pattern of hemispheric asymmetry, in both experiments. These findings show that in addition to the established right hemisphere dominance of the brain areas that direct attention, the consequences of directed attention may also be asymmetrical.     

Amburoside A, a glucoside from Amburanacearensis, protects mesencephalic cells against 6-hydroxydopamine-induced neurotoxicity

This study evaluates the potential neuroprotective properties of amburoside A, a glucoside isolated from Amburana cearensis, on rat mesencephalic cell cultures exposure to the neurotoxin 6-hydroxydopamine (6-OHDA). The parameters determined were cell viability by the 3[4,5-dimethylthiazole-2-il]-2,5-diphenyltetrazolium bromide (MTT) method, nitric oxide (NO) and free radical formation by the measurement of nitrite concentration and thiobarbituric acid reacting substance (TBARS) formation as an indication of cellular lipid peroxidation. The results showed that AMB was less effective as a curative agent in the MTT assay, since its addition after 6-OHDA did not reverse the neurotoxin's effect, except at the highest concentration (AMB, 100 microg/ml). Similarly, the higher nitrite levels observed after exposure of the cells to 6-OHDA were only partially reversed by AMB, at this highest concentration. However, when AMB (0.5, 1, 10 and 100 microg/ml) was added before the toxin, it appeared to protect neuronal cells against 6-OHDA toxicity in a concentration-dependent manner, as shown by MTT assay. AMB also prevented free radical formation indicated by the increased nitrite concentration induced by 6-OHDA. Cells exposed to 6-OHDA showed a 3.4 times increase in TBARS concentration as compared to controls, and this effect was inhibited from 24% up to 64% by AMB (0.1-100 microg/ml), indicative of a neuroprotective effect. In conclusion, we show that AMB, acting as an antioxidant compound, presents a significant neuroprotective effect, suggesting that this compound could provide benefits as a therapeutic agent in neurodegenerative disease such as Parkinson's.     

Modulation of brain activity by selective task sets observed using event-related potentials

We investigated the ability of subjects to shift dynamically between selective task sets, using informative trial-by-trial cues. Two tasks were used which involved non-overlapping neural systems and different hemispheric specialization. In a verbal task, subjects decided whether a letter string was a real word or a non-word. In a spatial task, subjects decided whether an angle was acute or obtuse. A behavioural experiment showed that performance improved when cues predicted the upcoming task (80% validity), compared to when neutral cues did not afford selective task sets. Event-related potentials (ERPs) revealed brain activity related to forming selective task expectations, to switching tasks, and to the modulation of target processing as a function of such expectations and switches. Activity predicting the probable task started over parietal electrodes 160 ms after cue presentation, while activity related to task switching started at frontal electrodes around 280 ms. Both types of activities developed before target onset. Target processing was significantly influenced by the validity of the cue prediction, including strong modulation of language-related potentials. These results show that it is possible to switch dynamically between task sets involving distinct neural systems, even before the appearance of an imperative target stimulus, and that the nature of the task sets can influence neural activity related to task-set reconfiguration. Selective task sets can in turn modulate the processing of target stimuli. The effects also apply to the case of foveally presented words, whose processing has often been hypothesized to be automatic and outside the influence of selective attention.     

Early-onset bacterial infection in Brazilian neonates with respiratory distress: a hospital-based study

We investigated infants with respiratory distress within 4 days of birth whose mothers had not received antibiotic prophylaxis to evaluate the frequency and etiology of bacterial infection and associated risk factors. The study was conducted on 261 infants suffering respiratory distress admitted to a Brazilian neonatal intensive care unit, 94 per cent of whom were born prematurely. Gestational and delivery history; bacteriological cultures of blood, cerebrospinal fluid, tracheal aspirates and urine; complete and differential blood counts; a urinary group B streptococcal latex antigen test; and a chest radiograph were analysed. Indications of infection were found in 38.7 per cent and confirmed in 11.9 per cent of the neonates. Gram-positive (70.9 per cent) and gram-negative bacteria (29.1 per cent) were found in 31 cases of confirmed early bacteremia. Group B Streptococcus was the predominant causative agent (19.4 per cent) in infants exhibiting confirmed infection. Culture-proven infection was more frequent among infants delivered vaginally (adjusted OR = 2.53, p = 0.05) or born to mothers with signs of intra-amniotic infection (adjusted OR = 2.83, p = 0.04). Preventive measures against early bacterial infection in preterm infants from this population are strongly warranted.     

Orienting attention to locations in internal representations

Three experiments investigated whether it is possible to orient selective spatial attention to internal representations held in working memory in a similar fashion to orienting to perceptual stimuli. In the first experiment, subjects were either cued to orient to a spatial location before a stimulus array was presented (pre-cue), cued to orient to a spatial location in working memory after the array was presented (retro-cue), or given no cueing information (neutral cue). The stimulus array consisted of four differently colored crosses, one in each quadrant. At the end of a trial, a colored cross (probe) was presented centrally, and subjects responded according to whether it had occurred in the array. There were equivalent patterns of behavioral costs and benefits of cueing for both pre-cues and retro-cues. A follow-up experiment used a peripheral probe stimulus requiring a decision about whether its color matched that of the item presented at the same location in the array. Replication of the behavioral costs and benefits of pre-cues and retro-cues in this experiment ruled out changes in response criteria as the only explanation for the effects. The third experiment used event-related potentials (ERPs) to compare the neural processes involved in orienting attention to a spatial location in an external versus an internal spatial representation. In this task, subjects responded according to whether a central probe stimulus occurred at the cued location in the array. There were both similarities and differences between ERPs to spatial cues toward a perception versus an internal spatial representation. Lateralized early posterior and later frontal negativities were observed for both pre- and retro-cues. Retro-cues also showed additional neural processes to be involved in orienting to an internal representation, including early effects over frontal electrodes.     

Brain activations during visual search: contributions of search efficiency versus feature binding

We investigated the involvement of the parietal cortex in binding features during visual search using functional magnetic resonance imaging. We tested 10 subjects in four visual search tasks across which we independently manipulated (1) the requirement to integrate different types of features in a stimulus (feature or conjunction search) and (2) the degree of search efficiency (efficient or inefficient). We identified brain areas that were common to all conditions of visual search and areas that were sensitive to the factors of efficiency and feature binding. Visual search engaged an extensive network of parietal, frontal, and occipital areas. The factor of efficiency exerted a strong influence on parietal activations along the intraparietal sulcus and in the superior parietal lobule. These regions showed a main effect of efficiency and showed a simple effect when inefficient conditions were compared directly with efficient pop-out conditions in the absence of feature binding. Furthermore, a correlation analysis supported a tight correspondence between posterior parietal activation and the slope of reaction-time search functions. Conversely, feature binding during efficient pop-out search was not sufficient to modulate the parietal cortex. The results confirm the important role of the parietal cortex in visual search, but suggest that feature binding is not a requirement to engage its contribution.