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PubMed2005

Attentional biases to internal and external sources of potential threat in social anxiety.

D. M. Clark and A. Wells (1995) proposed that a shift of attention inward toward interoceptive information is a central feature of social phobia. However, few studies have examined attentional biases toward internal physiological cues in social phobia. The current experiment assessed whether socially anxious individuals exhibit an attentional bias (a) toward cues for an internal source of potential threat (heart-rate information), (b) toward cues for an external source of potential threat (threatening faces) or (c) both. Ninety-one participants who were selected to form extreme groups based on a social anxiety screening measure performed a dot-probe task to assess location of attention. Results showed that socially anxious participants exhibited an attentional bias toward cues of internal, but not external, sources of potential threat.

Association↗

PubMed1979

The Alopex process: visual receptive fields by response feedback.

The determination of trigger features of single neurons in afferent pathways has been one of the central problems in sensory physiology. A novel method, called Alopex, has been developed, in which response feedback is used to construct visual patterns that optimize the responses. Data are presented which show the emergence of trigger features of cells monitored in frog visual tectum. The method id checked against results obtained by scanning the visual field with a small spot. Correlations between Alopex pattern and scann patterns are generally between 0.3 and 0.5 but may be as high as 0.9 when smoothing and/or averaging procedures are applied to the Alopex patterns. The dynamics of the Alopex process are discussed and details of the algorithms are presented. The series of experiments presented here has established the validity of the method and suggests that this approach should find wide application in receptive field studies. For that purpose data on the instrumentation and software are also presented.

Afferent Pathways↗

PubMed2000

Chylomicron processing in familial dysbetalipoproteinemia and familial combined hyperlipidemia studied with vitamin A and E as markers: a new physiological concept.

In previous work we identified a transfer/diffusion process occurring in the postprandial state that more or less contributes to the accumulation of beta-VLDL in familial dysbetalipoproteinemia (FD). Here we present a new theoretical concept underlying chylomicron processing developed on the basis of extended quantitative analyses of fat loading experiments, with both vitamins A and E, performed in patients with familial combined hyperlipidemia (FCH) in comparison to patients with FD and control subjects. Recovery of triglycerides from the fat load in the plasma triglyceride pool was <4%, indicating a very effective lipolysis process with an active remnant generation. Vitamin A from the fat load was, over 48 h, quantitatively recovered in the plasma lipoprotein pool; vitamin E was recovered to 2241%. Nevertheless, transfer/diffusion of both vitamins showed similar patterns. At equilibrium, their contents correlated strongly with the lipoprotein concentrations, the slopes being similar for control subjects and both groups of patients. Only in those FD patients with the highest lipid values, did the vitamin A/lipoprotein mass ratio in the Sf>100 fraction deviate from the total group mean. In the Sf 15-100 fraction, most specific for 'remnants', vitamin A/cholesterol ratios for all subjects were uniform proving that beta-VLDL formation is a thermodynamic process regulated by concentration gradients and the lipophilicity of lipoprotein constituents, not a typical feature for patients with FD. In patients with FD, vitamin A in the plasma pool was recovered excessively (276%) in line with recognition in various pools as a result of the transfer/diffusion process in plasma.

Adult↗

PubMed1989

Effects of phosphor persistence on perception and the control of eye movements.

When a rapid eye movement (saccade) is made across material displayed on cathode ray tube monitors with short-persistence phosphors, various perceptual phenomena occur. The phenomena do not occur when the monitor has a long-persistence phosphor. These phenomena were observed for certain spatial arrays, their possible physiological basis noted, and their effect on the control of eye movements examined. When the display consisted simply of two dots, and a saccade was made from one to the other, a transient ghost image was seen just beyond the destination target. When the display consisted of vertical lines, tilting and displacement of the lines occurred. The phenomena were more intrusive for the latter display and there was a significant increase in the number of corrective saccades. These results are interpreted in terms of the effects of fluctuating illumination (and hence phosphor persistence) on saccadic suppression.

Adult↗

PubMed2006

Electrophysiological correlates of similarity-based interference during detection of visual forms.

Illusory figure completion demonstrates the ability of the visual system to integrate information across gaps. Mechanisms that underlie figural emergence support the interpolation of contours and the filling-in of form information [Grossberg, S., & Mingolla, E. Neural dynamics of form perception: Boundary completion, illusory figures and neon colour spreading. Psychological Review, 92, 173-211, 1985]. Although both processes contribute to figure formation, visual search for an illusory target configuration has been shown to be susceptible to interfering form, but not contour, information [Conci, M., Müller, H. J., & Elliott, M. A. The contrasting impact of global and local object attributes on Kanizsa figure detection. Submitted]. Here, the physiological basis of form interference was investigated by recording event-related potentials elicited from contour- and surface-based distracter interactions with detection of a target Kanizsa figure. The results replicated the finding of form interference and revealed selection of the target and successful suppression of the irrelevant distracter to be reflected by amplitude differences in the N2pc component (240-340 msec). In conclusion, the observed component variations reflect processes of target selection on the basis of integrated form information resulting from figural completion processes.

Adult↗

PubMed1992

Behavioural and physiological evidence for covert face recognition in a prosopagnosic patient.

In a previous report, Bauer (1984) described the patient LF, who was unable to recognise familiar faces. Despite the inability to verbally identify familiar faces, psychophysiological examination revealed preserved covert processing of facial identity. Subsequent studies have demonstrated covert face recognition using behavioural tasks. Investigations of the patient PH showed normal face familiarity effects on matching, interference, priming, and learning tasks, while overt recognition was completely absent (De Haan, Young and Newcombe, 1987b). The use of different methodologies has led to different theoretical conceptualisation of the "covert recognition" phenomenon. Until now, no individual patient has been exposed to both methodologies. In this study we evaluated LF, who shows psychophysiological evidence of covert recognition, using behavioural tasks previously used with PH. The results reveal clear behavioural evidence of preserved face recognition without awareness. These findings suggest that both methodologies tap similar phenomena, and have important implications for theoretical models of covert face recognition. A conceptual model designed to integrate psychophysiological and behavioural evidence of covert face recognition is proposed.

Agnosia↗

PubMed2003

Olfaction and face encoding in humans: a magnetoencephalographic study.

Magnetic field changes were recorded while 20 healthy young participants performed a deep face encoding task. Some of the faces were randomly associated with a simultaneously presented odor. A recognition test, during which all faces were presented again together with the same number of new faces, followed. The task was to discriminate between repeated and new faces. During the recognition test no odor was presented. The recognition performance was significantly influenced by the simultaneously associated odor during the encoding phase. Faces associated with odor were less accurately recognized. In addition, we found significant physiological differences between 'encoded faces without odor' and 'encoded faces with odor'. In particular, two effects occurred. Between about 200 and 300 ms after stimulus onset 'encoded faces without odor' evoked higher brain activity than 'encoded faces with odor'. Between about 600 and 900 ms after stimulus onset 'encoded faces with odor' evoked higher brain activity than 'encoded faces without odor'. Whereas the latter effect is interpreted as reflecting conscious olfactory information processing, the earlier effect is suggested to reflect an odor influence on face encoding. We suggest that the simultaneous odor association distracted face encoding resulting in a significantly reduced recognition performance. These findings are suggested to represent evidence of multimodal sensoric interactions between visual face processing and olfactory information.

Adult↗

PubMed2003

Receptor subtypes: species variations in secretin affect potency for pancreatic but not gastric secretion.

INTRODUCTION: Receptor subtypes can be distinguished by different actions of agonists on physiologic responses. In this study, we compared effects of four species variants of secretin (rat, porcine, canine, and human) on pancreatic secretion and gastrin-induced acid secretion in urethane-anesthetized rats. These secretins differ by one to three residues in position 14, 15, or 16 and were used to probe for the presence of different secretin receptor subtypes in the rat. METHODOLOGY: Pancreatic responses were measured in a two-point parallel line bioassay with porcine secretin (3 and 30 pmol/kg IV bolus) as standard. Inhibition of gastric acid secretion by each secretin (100 pmol/[kg x h]) was quantitated against a threshold dosage of gastrin-17 (200 pmol/[kg x h]), and percent inhibition of incremental acid responses was determined. RESULTS: Rat secretin was significantly more potent than other secretins for pancreatic secretion, in the order of rat > porcine > canine > human. The four secretins significantly inhibited gastrin-induced acid secretion by 37% to 49%, with no statistically significant differences among the forms. CONCLUSIONS: Stimulation of pancreatic secretion was influenced by species variations in secretin structure, but inhibition of gastric acid secretion was not. This finding suggests that secretin receptor subtypes with different recognition patterns mediate these responses.

Amino Acid Sequence↗

PubMed1969

Reaction pattern to three stresses--electroplexy, surgery, and myocardial infarction--of fibrinolysis and plasma fibrinogen.

The effects of three types of stress-electroplexy, surgery, and myocardial infarction-on blood fibrinolytic activity and plasma fibrinogen levels were studied in 10, eight, and six patients respectively. The fibrinolytic response to electroplexy consisted of an initial short increase followed in half the patients by reduced fibrinolytic activity lasting two to four days. After surgery and myocardial infarction normal fibrinolytic activity was followed by a period of reduced activity; the timing of the measurements on these patients may have precluded recognition of an initial increase in fibrinolysis similar to that following electroplexy. The fibrinolytic ;shutdown' which lasted for about 10 days in the coronary patients was evidently due to reduction of plasminogen activator, as judged by prolongation of the euglobulin lysis times as well as of the blood clot lysis times. Plasma fibrinogen levels rose in the surgical and coronary patients but not in the patients given electroplexy which indicates that fibrinolytic activity changes independently of plasma fibrinogen level. The results suggest that the fibrinolytic system exhibits a common reaction pattern to stress, irrespective of its nature and of tissue damage. They call for caution in assuming a specific causal association in acute diseases such as pancreatitis and haematemesis where similar fibrinolytic changes may be encountered.

Adult↗

PubMed2005

Highly consistent patterns for inherited human diseases at the molecular level.

Over 1600 mammalian genes are known to cause an inherited disorder, when subjected to one or more mutations. These disease genes represent a unique resource for the identification and quantification of relationships between phenotypic attributes of a disease and the molecular features of the associated disease genes, including their ascribed annotated functional classes and expression patterns. Such analyses can provide a more global perspective and a deeper understanding of the probable causes underlying human hereditary diseases. In this perspective and critical view of disease genomics, we present a comparative analysis of genes reported to cause inherited diseases in humans in terms of their causative effects on physiology, their genetics and inheritance modes, the functional processes they are involved in and their expression profiles across a wide spectrum of tissues. Our analysis reveals that there are more extensive correlations between these attributes of genetic disease genes than previously appreciated. For instance, the functional pattern of genes causing dominant and recessive diseases is markedly different. Also, the function of the genes and their expression correlate with the type of disease they cause when mutated. The results further indicate that a comparative genomics approach for the analysis of genes linked to human genetic diseases will facilitate the elucidation of the underlying molecular and cellular mechanisms.

Biomarkers↗

PubMed1996

Spatial and temporal aspects of cellular calcium signaling.

Cytosolic Ca2+ signals are often organized in complex temporal and spatial patterns, even under conditions of sustained stimulation. In this review we discuss the mechanisms and physiological significance of this behavior in nonexcitable cells, in which the primary mechanism of Ca2+ mobilization is through (1,4,5)IP3-dependent Ca2+ release from intracellular stores. Oscillations of cytosolic free Ca2+ ([Ca2+]i) are a common form of temporal organization; in the spatial domain, these [Ca2+]i oscillations may take the form of [Ca2+]i waves that propagate throughout the cell or they may be restricted to specific subcellular regions. These patterns of Ca2+ signaling result from the limited range of cytoplasmic Ca2+ diffusion and the feedback regulation of the pathways responsible for Ca2+ mobilization. In addition, the spatial organization of [Ca2+]i changes appears to depend on the strategic distribution of Ca2+ stores within the cell. One type of [Ca2+]i oscillation is baseline spiking, in which discrete [Ca2+]i spikes occur with a frequency, but not amplitude, that is determined by agonist dose. Most current evidence favors a model in which baseline [Ca2+]i spiking results from the complex interplay between [Ca2+]i and (1,4,5)IP3 in regulating the gating of (1,4,5)IP3-sensitive intracellular Ca2+ channels. Sinusoidal [Ca2+]i oscillations represent a mechanistically distinct type of temporal organization, in which agonist dose regulates the amplitude but has no effect on oscillation frequency. Sinusoidal [Ca2+]i oscillations can be explained by a negative feedback effect of protein kinase C on the generation of (1,4,5)IP3 at the level of phospholipase C or its activating G-protein. The physiological significance of [Ca2+]i oscillations and waves is becoming more established with the observation of this behavior in intact tissues and by the recognition of Ca2+-dependent processes that are adapted to respond to frequency-modulated oscillatory [Ca2+]i signals. In some cells, these [Ca2+]i signals are targeted to control processes in limited cytoplasmic domains, and in other systems [Ca2+]i waves can be propagated through gap junctions to coordinate the function of multicellular systems.

Animals↗

PubMed2004

Initiation of endospore formation in Clostridium acetobutylicum.

Endospore formation in bacilli and clostridia shows remarkable similarities in morphology as well as in physiological and molecular biological cellular events. Major differences are the formation of clostridial stage cells and granulose accumulation in clostridia. In both genera, a cascade of sigma factors is activated after septation (by help of sigma(H) and Spo0A approximately P) in the sequence sigma(F), sigma(E), sigma(G), and sigma(K). Of these, sigma(F) and sigma(G) are active inside the forespore and are regulated by anti-sigma factors and anti-anti-sigma factors, whereas sigma(E) and sigma(K) (mother cell-specific sigma factors) are synthesized as precursor proteins and activated by proteolysis. Each of these sigma factors allows transcription of a specific set of genes and operons, thus leading to the orchestral expression of stage-specific proteins required for successful sporulation. Both, the genetic organization of the respective operons and the expression pattern of the sigma factors are very similar in Bacillus subtilis and Clostridium acetobutylicum, the model organisms of the two genera. However, a major regulatory difference is found in initiation of endospore formation. Genome sequencing revealed that clostridia do not contain components of the so-called phosphorelay, with the exception of the essential transcription factor Spo0A. This might reflect recognition of different environmental signals, as for clostridia nutrient limitation is no prerequisite for sporulation. In contrast to Bacillus, the clostridial sigH gene is constitutively expressed at a low level, with no increase at the onset of spore formation. The spo0A gene in C. acetobutylicum is also constitutively expressed, but Spo0A synthesis only occurs during the early and mid-exponential growth phase, indicating a posttranscriptional or cotranslational regulation. Mutational studies revealed an important regulatory function of a dual palindrome region upstream of the spo0A gene of C. acetobutylicum, part of which overlaps with a Spo0A-binding site. In addition to controlling sporulation genes, phosphorylated clostridial Spo0A is involved in regulation of acetone and butanol synthesis.

Journal Article↗

PubMed1993

Human Zn-alpha 2-glycoprotein: complete genomic sequence, identification of a related pseudogene and relationship to class I major histocompatibility complex genes.

The human gene (AZGP1) encoding Zn-alpha 2-glycoprotein (Zn-alpha 2-gp), a protein present in several biological fluids and produced by a subtype of breast carcinomas, has been cloned and its complete nucleotide sequence determined. The gene spans over 9.7 kb, and its overall organization and nucleotide sequence are very similar to those of the first four exons of class I MHC genes. However, the Zn-alpha 2-gp gene differs from these genes in several significant ways. It lacks the coding information for the transmembrane and cytoplasmic domains typical of MHC genes, which is consistent with its presence as a soluble protein in different physiological and pathological fluids. In addition, it contains a high density of repetitive sequences, including Alu, MER, and MIR elements, which are not present at equivalent positions in class I MHC genes. Finally, its 5'-flanking region lacks the class I MHC regulatory complex and the interferon consensus sequence characteristic of class I MHC genes. These findings may explain the different expression pattern of Zn-alpha 2-gp and class I MHC genes in human tissues. Southern blot hybridization of DNA from several species with a cDNA probe indicated that Zn-alpha 2-gp genes are present in a wide variety of animal species, including monkey, rat, mouse, dog, cow, and rabbit. The human genome also contains a putative Zn-alpha 2-gp pseudogene that has been isolated and partially characterized. This pseudogene has an intron-exon organization identical to that of the functional gene, but it presents two deleterious mutations in the third exon that lead to the appearance of premature stop codons. Finally, considering the lack of polymorphism in the Zn-alpha 2-gp gene in comparison with MHC genes, putative roles for this human glycoprotein in the transport of nonpolymorphic substances or in intercellular recognition processes are proposed.

Amino Acid Sequence↗

PubMed1994

Temporal summation of visual motion.

The sensitivity of the visual system to changes in velocity over time was investigated using the approach that Rashbass [(1970) Journal of Physiology, 210, 165-186] applied to luminance. Pairs of motion impulses (jumps) were presented, and thresholds for discriminating these pairs of impulses from a stationary display were determined. The results were consistent with a model that posits linear filtering of the input velocity, squaring, and integration over some duration. According to the model, the degree of interaction between the impulses reveals the autocorrelation of the impulse response of the motion system. The data were well fit by a three-element cascade of leaky integrators. In the temporal frequency domain, the visual motion system is a lowpass filter. This means that the visual system is quite insensitive to acceleration.

Discrimination, Psychological↗

PubMed2004

Visual lateralization in response to familiar and unfamiliar stimuli in fish.

Left- and right-monocular viewing during inspection of their own mirror-image was measured in fish (Xenopoecilus sarasinorum) that had been kept for 20 days in a tank with a mirror or in a tank in which conspecifics were visible behind a transparent glass partition. Results revealed a preferential use of the monocular visual field of the left eye in both conditions. The asymmetry was stronger during the first 5 min of observation and tended to fade slightly thereafter. In a second experiment left- and right-monocular viewing was measured in presence of artificial stimuli. Fish were kept for 20 days in a tank with either horizontal or vertical stripes positioned along one wall and then tested for eye use in a tank with a familiar (same orientation) or an unfamiliar (different orientation) pattern of stripes. Fish showed a preferential use of the monocular field of the left eye when presented with the familiar pattern and a slight preferential use of the right eye with the unfamiliar pattern. The former bias was stronger in the first minutes of test, after which it tended first to reverse and then to fade away; the latter bias, in contrast, appeared only after some minutes of observation. It is argued that the preferential use of the monocular visual field of the left eye (mainly serving structures located to the right side of the encephalon) is probably part of a more general specialization to establish identity, i.e. that an apparently familiar stimulus is indeed identical with one previously experienced. Preferential use of the monocular field of the right eye, in contrast, is argued to be associated with visual control of response.

Animals↗

PubMed1988

Heterogeneity of apolipoprotein E epitope expression on human lipoproteins: importance for apolipoprotein E function.

The conformations of apolipoproteins on the surfaces of lipoprotein particles affect their physiologic functions. The conformations of apoE on plasma lipoproteins were examined using a panel of eight anti-apoE monoclonal antibodies (MAbs). The antibodies, which reacted with the major isoforms of apoE (E2, E3, and E4), defined at least five epitopes on apoE. Proteolytic fragments and synthetic peptides of apoE were used in binding assays to assign antibody epitopes; the epitopes were all localized to the middle third of the apoE molecule. The expression of apoE epitopes on isolated apoE and on lipoproteins was probed in competitive microtiter plate immunoassays using the anti-apoE MAbs, 125I-labeled apoE as tracer, and isolated apoE, intermediate density (IDL), very low density (VLDL1-3), and high density (HDL2 and HDL3) lipoproteins as competitors. The antibodies determined the patterns of competition exhibited by the lipoprotein preparations. Antibodies of the IgM class (WU E-1, WU E-2, WU E-3) defined two sets of conformation-dependent epitopes that were assigned towards the middle and the carboxyl terminal of the middle third of apoE. Competition curves using these antibodies, apoE, and lipoproteins showed a large variability in ED50 values. MAbs WU E-4, WU E-7, and WU E-10 defined epitopes near the receptor recognition site on apoE. Competition curves demonstrated small ranges of ED50 values. MAbs WU E-11 and WU E-12, which defined epitopes toward the amino-terminal region of apoE, exhibited competition curves for apoE and lipoproteins that had consistent, but wider ranges of ED50 values. There was no strict relationship between lipoprotein flotation rates and epitope expression for any of the MAbs. Immunoaffinity chromatography of VLDL subfractions on four different MAb columns indicated that the differences in the competitive abilities of VLDL subfractions were partly due to heterogeneity of apoE epitope expression within any population of particles. VLDL particles specifically retained on two different anti-apoE MAb columns were better competitors than unretained fractions for 125I-labeled LDL binding to the apoB, E-receptor of cultured human fibroblasts, suggesting that increased accessibility of apoE on the surface of VLDL is associated with increased receptor recognition. These data suggest that individual epitopes of apoE can be modulated; epitope expressions are not determined solely by the sizes and/or densities of lipoprotein particles; and differences in apoE conformation have significant metabolic consequences.

Antibodies, Monoclonal↗

PubMed1976

Continuous dynamic monitoring of pressure and flow patterns during assisted ventilation.

A system for continuous, dynamic monitoring of children requiring ventilatory assistance has been developed and used in a critical care setting. Breath by breath airway pressure changes are measured on a specially adapted meter with high-and low-pressure limit alarms, and are displayed graphically on a bedside oscilloscope. This system has proved to be beneficial in detecting ventilator system malfunction; in adjusting ventilator settings, such as inspiratory/expiratory ratios, end-expiratory pressure, and phase duration and flow ratios; in assessing compliance of a child requiring ventilatory assistance and his capability for spontaneous breathing; and in the early recognition of potentially harmful problems attendant upon assisted ventilation. The system provides additional educational benefit for the I.C.U. personnel, who become more knowledgeable regarding ventilatory problems, and more apt to discover them promptly. The simplicity of the system, compatibility with other I.C.U. monitoring equipment, capability for continuous, dynamic monitoring, and broad scope recommended it for infants and children requiring assisted ventilation.

Child↗

PubMed1984

Molecular heterogeneity of canine cholecystokinin in portal and peripheral plasma.

The release of molecular forms of cholecystokinin (CCK) into the portal and peripheral blood in response to an intraduodenal perfusion of sodium oleate (9 mmol X h-1) was studied in six conscious dogs with chronic portal vein catheters. Immunoreactive CCK as concentrated from 20 ml plasma by C18 SEP PAK cartridges and the pattern of molecular forms of CCK were studied by G50 gel filtration. CCK-like immunoreactivity (CCK-LI) was measured in the column eluates with antibody 5135, which measures gastrin and CCK equally and requires the intact carboxyl-terminus for full recognition. Gastrin was measured specifically with antibody 1611. Intraduodenal perfusion with oleate did not alter basal gastrin release. Release of CCK-LI by intraduodenal oleate was calculated by the increments of the integrated CCK-LI peaks over basal. Total CCK-like immunoreactivity (CCK-LI), calculated by integration of all CCK-LI peaks in gel filtration eluates, increased over basal by 12 fmol/ml in the portal and by 6 fmol/ml in the peripheral plasma after intraduodenal perfusion with sodium oleate. The main molecular forms eluted on gel filtration in positions of CCK33,39 and of CCK8. The pattern of CCK in the peripheral plasma was similar to that in the portal plasma except that in the peripheral plasma large molecular forms were more abundant than small forms. This finding was confirmed when CCK39 and CCK8 were infused either into the portal vein or into the peripheral vein and peripheral plasma CCK levels were measured. Elimination of CCK8 after portal vein infusion compared to peripheral vein infusion was about 3 times higher than that of CCK39. The abundance of large molecular forms of CCK in the circulating blood which are similar in potency to small forms, underlines their role in the physiology of CCK.

Animals↗