Platelet adhesion and fibrinogen deposition in murine microvessels upon inhalation of nanosized carbon particles.

SUMMARY BACKGROUND: The translocation of nanoparticles in the lung toward effector organs via the circulation is considered an important direct pathway for systemic effects of nanoparticles after inhalation. Recently, we have reported that a moderate dose of systemically administered nanosized carbon black particles exerted thrombogenic effects in hepatic microvessels of healthy mice. OBJECTIVES: This study addresses the questions of whether similar thrombogenic effects are also evoked upon inhalation of nanosized carbon particles (NCP) and whether NCP-induced hepatic platelet accumulation is associated with pulmonary or systemic inflammation. METHODS: Two and 8 h after a 24-h exposure to either filtered air or to NCP, intravital fluorescence microscopy of the hepatic microcirculation was performed in C57Bl/6 mice. Parameters of pulmonary or systemic inflammatory response were determined in bronchoalveolar lavage and blood/plasma samples. RESULTS: Inhalative exposure to NCP caused platelet accumulation in the hepatic microvasculature, whereas leukocyte recruitment and sinusoidal perfusion did not differ from controls. Fibrinogen deposition was detected by immunohistochemistry in both hepatic and cardiac microvessels from NCP-exposed mice. In contrast, inhalation of NCP affected neither the plasma levels of proinflammatory cytokines nor blood cell counts. Moreover, the bronchoalveolar lavage data indicate that no significant inflammatory response occurred in the lung. CONCLUSIONS: Thus, exposure to NCP exerts thrombogenic effects in the microcirculation of healthy mice independent of the route of administration (i.e. inhalation or systemic intra-arterial administration). The NCP-induced thrombogenic effects are not liver specific, are associated with neither a local nor a systemic inflammatory response, and seem to be independent of pulmonary inflammation.

fMLP-induced respiratory burst and the intracellular Ca2+ signal are not interrelated in neutrophils.

Reactive oxygen intermediate (ROI) production and the development of the intracellular (IC) Ca2+ ([Ca2+]i) signal by formyl-Met-Leu-Phe (fMLP) stimuli were investigated in neutrophils. When the concentration was varied between 2.3 nM-2.3 microM, ROI production and the [Ca2+]i signal showed different fMLP concentration dependencies. ROI production increased continuously with increasing fMLP concentrations, while the [Ca2+]i signal responses reached a plateau around 230 nM fMLP. Moreover, when a consecutive, 2.3 microM fMLP stimulus was applied 10 min after the first fMLP stimulus, the intensity of the ROI production and that of the [Ca2+]i signal showed a variable dependence on the fMLP concentration of the first stimulus. An initial fMLP dose of 2.3 nM and 23 nM sensitized the cells regarding their ROI production and [Ca2+]i signals. After a first fMLP stimulus of 230 nM, the second stimulus produced an increased [Ca2+]i signal, while no ROI production could be activated. A strong fMLP stimulus of 2.3 microM desensitized the cells regarding both [Ca2+]i signal and ROI production. However, even in these desensitized cells, a high level of ROI production could be evoked by other stimuli like PMA or opsonized zymosan. The differences observed between the fMLP concentration dependence of ROI production and the [Ca2+]i signal strongly suggest that these two phenomena are not interrelated.

Azurophil granules are heterogeneous with respect to mobilization induced by different concentrations of fMLP.

Azurophil granules of neutrophils beyond their already known heterogeneity of beta-glucuronidase and myeloperoxidase enzyme contents are heterogeneous with respect to a spontaneous or low concentration (2.3 or 23 nM) of formyl-Met-Leu-Phe-induced mobilization. This suggests that the heterogeneity of azurophil granules is manifested in their functions too.

A common perceptual space for harmonic and percussive timbres.

The goal of a series of listening tests was to better isolate the principal dimensions of timbre, using a wide range of timbres and converging psychophysical techniques. Expert musicians and nonmusicians rated the timbral similarity of three sets of pitched and percussive instruments. Multidimensional scaling analyses indicated that both centroid and rise time comprise the principal acoustic factors across all stimulus sets and that musicians and nonmusicians did not differ significantly in their weighting of these factors. Clustering analyses revealed that participants also categorized percussive and, to a much lesser extent, pitched timbres according to underlying physical-acoustic commonalties. The findings demonstrate that spectral centroid and rise time represent principal perceptual dimensions of timbre, independent of musical training, but that the tendency to group timbres according to source properties increases with acoustic complexity.

Haptic form perception: relative salience of local and global features.

When we examine objects haptically, do we weight their local and global features as we do visually, or do we place relatively greater emphasis on local shape? In Experiment 1, subjects made either haptic or visual comparisons of pairs of geometric objects (from a set of 16) differing in local and global shape. Relative to other objects, those with comparable global shape but different local features were judged less similar by touch than by vision. Separate groups of subjects explored the same objects while wearing either thick gloves (to discourage contour-following) or splinted gloves (to prevent enclosure). Ratings of similarity were comparable in these two conditions, suggesting that neither exploratory procedure was necessary, by itself, for the extraction of either local or global shape. In Experiment 2, haptic exploration time was restricted to 1, 4, 8, or 16 sec. Limiting exploration time affected relative similarity in objects differing in their local but not their global shape. Together, the findings indicate that the hepatic system initially weights local features more heavily than global ones, that this differential weighting decreases over time, and that neither contour-following nor enclosure is exclusively associated with the differential emphasis on local versus global features.

A multimodal assessment of sensory thresholds in aging.

Young and elderly subjects yielded forced-choice detection thresholds in each of seven sensory tasks: (1) taste of sodium chloride, (2) smell of butanol, (3) cooling, (4) low-frequency vibrotaction, (5) high-frequency vibrotaction, (6) low-frequency hearing, and (7) high-frequency hearing. Average scores across these tasks nearly perfectly separated the 22 elderly from the 15 young subjects. For individual modalities, however, separation between the groups varied from complete (high-frequency touch) to negligible (low-frequency hearing). Scores on the Boston Picture Naming Test and especially the Wechsler Logical Memory Test correlated strongly with average threshold score (Pearson r = .80) and moderately with scores on individual modalities. This sensory-cognitive link is not caused, as might be supposed, by diminishing age-related capacity to handle the detection task, because the very same task resulted in negligible age effect (low-frequency hearing) and large effect (high-frequency hearing) in the same subjects.

Drought stress, peroxidase activity and formaldehyde metabolism in bean plants.

In our investigations we have studied the changes of total peroxidase and isozyme activities, peroxidase isozyme pattern and the level of endogenous formaldehyde and trigonelline. We have examined the effect of drought stress resulted by Carbowax treatment (2, 5, 7, 10%) of two different snap bean (Phaseolus vulgaris L.) genotypes [drought tolerant (T) and drought sensitive (S)]. There were no detectable differences in the peroxidase isozyme patterns but the total peroxidase activity was increased. We have found similar steep enhancement in the peroxidase activities of one of three peroxidase fractions while the increase in the other isozyme fractions was not so significant in the two genotypes. Increasing peroxidase activities and changes in the amount of endogenous formaldehyde and trigonelline were detectable with increasing Carbowax treatment in both genotypes, but in different ways. According to our experiments, the total peroxidase and some isozyme activity correlated with the concentration of endogenous formaldehyde and trigonelline, playing an important role during drought stress.

Haptic underestimation of angular extent.

To what extent can individuals accurately estimate the angle between two surfaces through touch alone, and how does tactile judgment compare to visual judgment? Subjects' ability to estimate angle size for a variety of haptic and visual stimuli was examined in a series of nine experiments. Triangular wooden blocks and raised contour outlines comprising different angles and radii of curvature at the apex were used in experiments 1-4 and it was found that subjects consistently underestimated angular extent relative to visual baselines and that the degree of underestimation was inversely related to the actual size of the angle. Angle estimates also increased with increasing radius of curvature when actual angle size was held constant. In contrast, experiments 5-8 showed that subjects did not underestimate angular extent when asked to perform a haptic-visual match to a computerized visual image; this outcome suggests that visual input may 'recalibrate' the haptic system's internal metric for estimating angle. The basis of this cross-modal interaction was investigated in experiment 9 by varying the nature and extent of visual cues available in haptic estimation tasks. The addition of visual-spatial cues did not significantly reduce the magnitude of haptic underestimation. The experiments as a whole indicate that haptic underestimations of angle occur in a number of different stimulus contexts, but leave open the question of exactly what type of visual information may serve to recalibrate touch in this regard.

The representation of auditory source characteristics: simple geometric form.

Two experiments examined listeners' ability to discriminate the geometric shape of simple resonating bodies on the basis of their corresponding auditory attributes. In cross-modal matching tasks, subjects listened to recordings of pairs of metal bars (Experiment 1) or wooden bars (Experiment 2) struck in sequence and then selected a visual depiction of the bar cross sections that correctly represented their relative widths and heights from two opposing pairs presented on a computer screen. Multidimensional scaling solutions derived from matching scores for metal and wooden bars indicated that subjects' performance varied directly with increasing differences in the width/height (W/H) ratios of both sets of bars. Subsequent acoustic analyses revealed that the frequency components from torsional vibrational modes and the ratios of frequencies of transverse bending modes in the bars correlated strongly with both the bars' W/H ratios and bar coordinates in the multidimensional configurations. The results suggest that listeners can encode the auditory properties of sound sources by extracting certain invariant physical characteristics of their gross geometric properties from their acoustic behavior.

Constraints common to apparent motion in visual, tactile, and auditory space.

A point-like stimulus was presented in a clockwise or counterclockwise sequence at 3, 4, 6, or 12 uniformly spaced locations around a circle in visual, tactile, or auditory space. In 4 experiments, the stimulators were (a) light-emitting diodes in the frontal plane, (b) mechanical stimulators on the palm, (c) airpuff nozzles around the head, and (d) loudspeakers around the head. For each spatial separation and stimulus-onset asynchrony (SOA) between successive stimuli around the circle, participants reported the direction of motion. Within each modality, the SOA required for 75% accurate discrimination of direction increased with the spatial separations. A time-distance constraint akin to Korte's third law of visual apparent motion can thus be obtained from responses that are objectively classifiable as correct or incorrect (without relying on subjective reports of "goodness" of apparent motion). Moreover, this time-distance constraint evidently generalizes across sensory modalities.

Time-distance relations in shifting attention between locations on one's body.

Does the time to discriminate the presence or absence of a tactile stimulus depend on its distance from the bodily location to which one has been attending? Subjects were tested by the presentation of air puffs at four of eight possible locations on the body. In each trial of Experiment 1, (1) subjects attended auditorily to an announcement of one of the eight locations; (2) 2 sec later, a second location was announced and, simultaneously, air puffs were presented at a randomly selected four of the eight locations; (3) the subjects reported as quickly as possible on whether or not air puffs had been presented at the second-announced location. Overall, reaction times increased with the distance between the just-attended and the tested locations. Experiment 2 was undertaken to determine whether the operative distance was distance through the subject's body or directly through three-dimensional space. The subjects were tested as in Experiment 1, but with their arms and legs either side-by-side in front or spread out to each side. Reaction times then depended more on straight-line distance in space than on distance through the body.

Noncovalent interactions in maintaining the native structure of low density lipoprotein.

The integrity and the surface charge distribution of native low density lipoprotein (LDL) are prerequisites of its binding to the LDL receptor. Oxidation is one of the most important physiological effects resulting in an altered structure and metabolism of LDL. To reveal forces responsible for maintaining the intact structure of LDL in the absence of cells we have determined the kinetics of lipid peroxidation, changes in electrophoretic mobilities and size distributions of LDL samples as a function of Cu++ induced oxidative modification in a cell-free system at two different (50 mM and 150 mM) ionic strengths by electrophoretic and dynamic light scattering. Our data show that the lipid peroxidation is almost complete before LDL is degraded at 50 mM while a slight extent of lipid peroxidation is enough to result in the same effect at 150 mM. These suggest that both ionic and hydrophobic interactions are necessary to maintain the integrity of the LDL molecule.

The influence of visual cues on the localisation of circular auditory motion.

A relative inability of listeners to refer auditory motion properly to the front hemifield when a rapid circular trajectory is traced around them in the horizontal plane was investigated. It was hypothesised that the representations of visual space and auditory frontal space are linked in such a way that auditory cues alone are insufficient to determine the veridical path in the front hemifield when both the front and the rear hemifield receive circular auditory input in rapid sequence. Listeners discriminated the direction of a rapid apparent trajectory created by the sequential activation of various combinations of loudspeakers and light-emitting diodes spaced evenly in a circular array. The addition of visual stimuli to the front hemifield, even when lacking motional cues, improved discrimination significantly. Conversely, when the same portion of the trajectory presented to the front hemifield consisted only of visual stimuli, performance decreased markedly. Additional conditions, in which the trajectory was restricted to a 120 deg path in the frontal plane, confirmed these effects. The findings suggest that the presence of a visual cue enhances the perception of auditory directionality, even when it does not itself provide any motion information.

Temporal constraints on apparent motion in auditory space.

The hypothesis that the extent of spatial separation between successive sound events directly affects the perception of time intervals between these events was tested using an apparent motion paradigm. Subjects listened to four-tone pitch patterns whose individual tones were sounded alternately at one of two loudspeaker positions, and they adjusted the alternation rate until they could no longer distinguish the four-tone ordering of the pattern. Four horizontal and two vertical loudspeaker separations were tested. Results indicate a direct relation between horizontal separation and the critical stimulus onset asynchrony (SOA) between successive tones within a pattern. At the critical SOA, subjects reported hearing not a four-tone pattern, but two pairs of two-note groups overlapping in time. The findings are discussed in the context of auditory spatial processing mechanisms and possible sensory-specific representational constraints.

Recognition of complex auditory-spatial patterns.

Two experiments were carried out to investigate the perception of complex auditory-spatial patterns. Subjects were asked to identify alphanumeric characters whose patterns could be outlined acoustically through the sequential activation of specific units in a speaker array. Signal bandwidths were varied systematically in both experiments. Signals in experiment 1 had sharp onsets and offsets; envelope shapes in experiment 2 were much more gradual. Subjects showed considerable ability in recognizing alphanumeric patterns traced with signals of varying acoustical composition. Reductions in the steepness of signal attack and decay produced limited declines in pattern recognition ability. Systematic trends in the relation between patterns and the distribution of incorrect responses suggest that subjects performed a pattern-matching task, in which identifications were made on the basis of component features. The unexpected pattern recognition abilities that subjects demonstrated in both experiments suggest that spatial hearing, like vision, has access to mechanisms for amodal spatial representations.

[Exocrine pancreas involvement in chronic enteropathies in infants and children]. / Suferinta pancreasului exocrin în enteropatiile cronice ale sugarului si copilului.

On a number of 135 cases of chronic enteropathies in patients aged 6 months--15 years, the trypsin, amilasis and lipasis levels in duodenal aspirate were investigated. In a high number, the decrease of pancreatic enzymes activity was noted and the majority of cases were accompanied by a marked dystrophy (grades II or III). Thus, it was not possible to indicate whether the low levels were primary or secondary determined.

[The celiac syndrome. The clinico-histological correlations]. / Sindromul celiac. Corelatii clinico-histologice.

The authors studied a number of 445 children with malabsorption in which a jejunal biopsy was done. Concerning the celiac disease, they emphasized the value of jejunal biopsy in diagnosis and monitoring the treatment.

[Ultrastructural changes in the gastric mucosa in chronic gastritis in children]. / Modificari ultrastructurale ale mucoasei gastrice în gastrita cronica a copilului.

Studying a series of 30 children with chronic gastritis (diagnosed by optic fiber gastroscopy and by mucosal biopsy), authors have founded important changes of the superficial mucosa and gastric glands. The histologic changes could explain the well-known functional alterations in chronic gastritis. They discussed also a possible immuno-pathogenic mechanism for these mucosal ultrastructural changes.

Interactions between globular proteins and F-actin in isotonic saline solution.

Solutions of each of three different globular proteins (cytochrome c, chromophorically labeled serum albumin, and chromophorically labeled aldolase), mixed with another unlabeled globular protein or with fibrous actin, were prepared in pH 8.0 Tris-HCl buffer containing 0.15 M NaCl. Each solution was centrifuged at low speed, at 5 degrees C, until unassociated globular protein in solution achieved sedimentation equilibrium. Individual absorbance gradients of both macrosolutes in the mixtures subsequent to centrifugation were obtained via optical scans of the centrifuge tubes at two wavelengths. The gradients of each macrosolute in mixtures of two globular proteins revealed no association of globular proteins under the conditions of these experiments, but perturbation of the gradients of serum albumin, aldolase, and cytochrome c in the presence of F-actin indicated association of all three globular proteins with F-actin. Perturbation of actin gradients in the presence of serum albumin and aldolase suggested partial depolymerization of the F-actin by the globular protein. Analysis of the data with a simple phenomenological model relating free globular protein, bound globular protein, and total actin concentration provided estimates of the respective equilibrium constants for association of serum albumin and aldolase with F-actin, under the conditions of these experiments, of the order of 0.1 microM-1.