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PubMed1976

Changes in the electric dipole vector of human serum albumin due to complexing with fatty acids.

The magnitude of the electric dipole vector of human serum albumin, as measured by the dielectric increment of the isoionic solution, is found to be a sensitive, monotonic indicator of the number of moles (up to at least 5) of long chain fatty acid complexed. The sensitivity is about three times as great as it is in bovine albumin. New methods of analysis of the frequency dispersion of the dielectric constant were developed to ascertain if molecular shape changes also accompany the complexing with fatty acid. Direct two-component rotary diffusion constant analysis is found to be too strongly affected by cross modulation between small systematic errors and physically significant data components to be a reliable measure of structural modification. Multicomponent relaxation profiles are more useful as recognition patterns for structural comparisons, but the equations involved are ill-conditioned and solutions based on standard least-squares regression contain mathematical artifacts which mask the physically significant spectrum. By constraining the solution to non-negative coefficients, the magnitude of the artifacts is reduced to well below the magnitudes of the spectral components. Profiles calculated in this way show no evidence of significant dipole direction or molecular shape change as the albumin is complexed with 1 mol of fatty acid. In these experiments albumin was defatted by incubation with adipose tissue at physiological pH, which avoids passing the protein through the pH of the N-F transition usually required in defatting. Addition of fatty acid from soluion in small amounts of ethanol appears to form a complex indistinguishable from the "native" complex.

Binding Sites↗
PubMed2006

Fetal hypoxic and ischemic injuries.

PURPOSE OF REVIEW: The principles of neonatal neurological protection following intrapartum hypoxia are briefly reviewed. The physiological principles behind the use of cardiotocograph patterns in defining the timing and mechanism of fetal hypoxia and injury are then demonstrated. RECENT FINDINGS: Fetal neurological injury may result from progressive hypoxemia, acidosis, diminished cardiac output and cerebral ischemia, manifested at birth as low Apgar scores, multisystem compromise, severe acidosis and encephalopathy. More commonly, however, intrapartum injury results from often intermittent, regional ischemia secondary to umbilical cord or head compression resulting in hemorrhage or infarction. Under these circumstances, the amount of umbilical acidosis and neonatal encephalopathy varies and the potential candidate for neuroprotection may escape recognition and timely treatment. Selecting infants likely to benefit from neuroprotection requires information on the timing, duration and mechanism of hypoxia. Neonatal parameters, including low Apgar scores, acidosis, even seizures, lack sensitivity and specificity. Cardiotocograph patterns are capable of determining the duration, mechanism and severity of hypoxia and occasionally, the timing of neurological injury. SUMMARY: Protecting the newborn from the neurological consequences of intrapartum hypoxia requires critical definition of the mechanism and timing of this exposure. cardiotocograph tracings offer the opportunity to refine the selection of candidates for neonatal rescue.

Cardiotocography↗
PubMed2004

Bilateral mesial temporal lobe epilepsy: comparison of scalp EEG and hippocampal MRI-T2 relaxometry.

OBJECTIVE: Bilateral hippocampal abnormality is frequent in mesial temporal lobe sclerosis and might affect outcome in epilepsy surgery. The objective of this study was to compare the lateralization of interictal and ictal scalp EEG with MRI T2 relaxometry. MATERIAL AND METHODS: Forty-nine consecutive patients with intractable mesial temporal lobe epilepsy (MTLE) were studied with scalp EEG/video monitoring and MRI T2 relaxometry. RESULTS: Bilateral prolongation of hippocampal T2 time was significantly associated with following bitemporal scalp EEG changes: (i) in ictal EEG left and right temporal EEG seizure onsets in different seizures, or, after regionalized EEG onset, evolution of an independent ictal EEG over the contralateral temporal lobe (left and right temporal asynchronous frequencies or lateralization switch; P = 0.002); (ii) in interictal EEG both left and right temporal interictal slowing (P = 0.007). Bitemporal T2 changes were not, however, associated with bitemporal interictal epileptiform discharges (IED). Lateralization of bilateral asymmetric or unilateral abnormal T2 findings were associated with initial regionalization of the ictal EEG in all but one patient (P < 0.005), with lateralization of IED in all patients (P < 0.005), and with scalp EEG slowing in 28 (82,4%) of 34 patients (P = 0.007). CONCLUSION: Our data suggest that EEG seizure propagation is more closely related to hippocampal T2 abnormalities than IED. Interictal and ictal scalp EEG, including the recognition of ictal propagation patterns, and MRI T2 relaxometry can help to identify patients with bitemporal damage in MTLE. Further studies are needed to estimate the impact of bilateral EEG and MRI abnormal findings on the surgical outcome.

Action Potentials↗
PubMed2002

Growth and failure to thrive.

Monitoring of growth in early life is particularly important as growth is elastic and sensitive to environmental factors, especially nutrition. Deficits are unlikely to be recovered fully in a later period and early growth patterns contribute to many diseases of adulthood. Assessment of rate of growth, rather than attained size, is possible with today's charts and accurate measurement. Growth monitoring is important for recognition of failure to thrive and it is valuable as a proxy measure for wellbeing. Many factors can contribute to failure to thrive which is best managed using a multidisciplinary approach.

Body Height↗
PubMed2006

Perceptual adaptation to spectrally shifted vowels: training with nonlexical labels.

Although normal-hearing (NH) and cochlear implant (CI) listeners are able to adapt to spectrally shifted speech to some degree, auditory training has been shown to provide more complete and/or accelerated adaptation. However, it is unclear whether listeners use auditory and visual feedback to improve discrimination of speech stimuli, or to learn the identity of speech stimuli. The present study investigated the effects of training with lexical and nonlexical labels on NH listeners' perceptual adaptation to spectrally degraded and spectrally shifted vowels. An eight-channel sine wave vocoder was used to simulate CI speech processing. Two degrees of spectral shift (moderate and severe shift) were studied with three training paradigms, including training with lexical labels (i.e., "hayed," "had," "who'd," etc.), training with nonlexical labels (i.e., randomly assigned letters "f," "b," "g," etc.), and repeated testing with lexical labels (i.e., "test-only" paradigm without feedback). All training and testing was conducted over 5 consecutive days, with two to four training exercises per day. Results showed that with the test-only paradigm, lexically labeled vowel recognition significantly improved for moderately shifted vowels; however, there was no significant improvement for severely shifted vowels. Training with nonlexical labels significantly improved the recognition of nonlexically labeled vowels for both shift conditions; however, this improvement failed to generalize to lexically labeled vowel recognition with severely shifted vowels. Training with lexical labels significantly improved lexically labeled vowel recognition with severely shifted vowels. These results suggest that storage and retrieval of speech patterns in the central nervous system is somewhat robust to tonotopic distortion and spectral degradation. Although training with nonlexical labels may improve discrimination of spectrally distorted peripheral patterns, lexically meaningful feedback is needed to identify these peripheral patterns. The results also suggest that training with lexically meaningful feedback may be beneficial to CI users, especially patients with shallow electrode insertion depths.

Adaptation, Physiological↗
PubMed1989

Sports nutrition. Approaching the nineties.

A sophisticated appreciation of the role of nutrition in athletic performance has been made possible by increasing knowledge of the physiology of exercise. The nutritional issues of training are of primary importance, since this occupies most of the athlete's effort. The nutritional support of an intense daily training programme includes an appropriately high energy intake, predominantly in the form of carbohydrate in order to continually replenish muscle glycogen stores. Recent review of the protein needs of athletes indicates that requirements may be substantially above those of sedentary subjects, to account for the oxidation of amino acids during exercise as well as the retention of nitrogen during periods of muscle building. However, these increased requirements are likely to be met by the generous protein intakes anticipated in a high energy diet. The same would seem to hold true for micronutrient considerations, although there is no evidence that vitamin requirements are considerably increased by exercise. Nevertheless, a high energy diet chosen from a sufficiently varied range of foods should allow micronutrient intakes well in excess of population recommended dietary intake levels. Current interest is focused on the mineral status of athletes, particularly that of iron and calcium. In the case of iron, there is a possibility that the increased level of loss by some endurance athletes will not be met by their usual dietary patterns. Screening for early signs of iron deficiency, and appropriate supplementation and dietary counselling seem warranted in high risk groups. Competition poses the challenge of identifying possible factors limiting performance, and taking steps to delay or reduce these. Of paramount importance is body temperature regulation through the maintenance of hydration levels. This issue has long been recognised, but recent studies of gastric emptying and the benefits of carbohydrate supplementation during exercise have caused an update of the advice to athletes regarding fluid intake during exercise. It now seems possible to simultaneously achieve fluid and carbohydrate requirements for endurance exercise within a wide range of choice of beverages containing up to 10% carbohydrate. Concern about the adequacy of carbohydrate fuel stores in endurance exercise situations is also well known. The recognition that training achieves various physiological adaptations to enhance the lifespan of fuel stores has taken away some of the attention previously focussed on carbohydrate-loading techniques.(ABSTRACT TRUNCATED AT 400 WORDS)

Humans↗
PubMed1984

A multiple-channel model for grating detection.

The multiple-channel model that was proposed in 1974 by MacLeod and Rosenfeld to describe the sensitivity of the visual system to complex gratings has been applied to a variety of complex gratings. The model predicts correctly the contrast sensitivity at both high and low spatial frequencies to square-wave gratings, square-wave with missing fundamental, sawtooth-wave, and trapezoid-wave gratings of different ramp widths. It provides a physiologically reasonable explanation of the detection of luminance gradients without requiring special gradient detectors. The model resembles the threshold behavior of the visual system in that it is sensitive to the relative phase of frequency components at low frequencies, but not at high frequencies.

Form Perception↗
PubMed1997

An electrophysiological metric of activity within the ON- and OFF-pathways in humans.

Several animal studies have shown an anatomical and functional separation between the ON- and OFF-pathways in the retina and in the lateral geniculate nucleus. Psychophysical studies in humans have also documented separate pathways that process increments and decrements of light. However, at the level of the visual cortex, there is electrophysiological evidence of interactions between the ON- and OFF-pathways. In addition, psychophysical studies have shown that these pathways can exhibit differential sensitivity and be differentially adapted. These findings motivated an electrophysiological study to gather further evidence of processing within the ON- and OFF-pathways in the human visual system. Using sawtooth stimulus modulation, we measured the visual evoked potential (VEP) before and after adaptation to both rapid-on and rapid-off sawtooth stimuli. The effect of adaptation was determined by comparing the VEP response in three test conditions: without adaptation, after adaptation to the same sawtooth polarity, and after adaptation to the opposite sawtooth polarity. The results reveal a selective adaptation effect, which provides physiological evidence for separate processing of increments and decrements in the human visual system. We conclude that with appropriate stimulus parameters, the VEP can serve as an objective measure of processing within the ON- and OFF-pathways in humans.

Adaptation, Ocular↗
PubMed2005

Colour helps to solve the binocular matching problem.

The spatial differences between the two retinal images, called binocular disparities, can be used to recover the three-dimensional (3D) aspects of a scene. The computation of disparity depends upon the correct identification of corresponding features in the two images. Understanding what image features are used by the brain to solve this binocular matching problem is an important issue in research on stereoscopic vision. The role of colour in binocular vision is controversial and it has been argued that colour is ineffective in achieving binocular vision. In the current experiment subjects were required to indicate the amount of perceived depth. The stimulus consisted of an array of fronto-parallel bars uniformly distributed in a constant sized volume. We studied the perceived depth in those 3D stimuli by manipulating both colour (monochrome, trichrome) and luminance (congruent, incongruent). Our results demonstrate that the amount of perceived depth was influenced by colour, indicating that the visual system uses colour to achieve binocular matching. Physiological data have revealed cortical cells in macaque V2 that are tuned both to binocular disparity and to colour. We suggest that one of the functional roles of these cells may be to help solve the binocular matching problem.

Color↗
PubMed2005

The antimicrobial properties of C-reactive protein (CRP).

C-reactive protein, CRP, is a predominant pattern-recognition receptor (PRR) in the plasma of the horseshoe crab, which recognizes lipopolysaccharide (LPS). Native CRP2 has previously been shown to exhibit agglutination activity against the polysialic capsule of Escherichia coli K1 but its role in bacterial clearance is not well characterized. In this work, the antimicrobial activity of a recombinant CRP2 isoform (rCRP2) was tested against E. coli, Pseudomonas aeruginosa and Staphylococcus aureus. rCRP2 agglutinates bacteria and exhibits bactericidal activity against Gram-negative bacteria. In addition, the antimicrobial activity of rCRP2 is calcium-independent. GST pulldown experiments suggest that in the naïve physiological state, CRP2 interacts with hemocyanin, native CRPs, a 35-kDa plasma lectin and an as yet unidentified 40-kDa protein. This interaction was enhanced upon Pseudomonas infection. We propose that rCRP2 is a PRR with potent antimicrobial activity and its interacting partners contribute to effective bacterial clearance.

Agglutination Tests↗
PubMed2000

A central-peripheral asymmetry in masked priming.

Masked primes presented prior to a target result in behavioral benefits on incompatible trials (in which the prime and the target are mapped onto opposite responses) when they appear at fixation, but in behavioral benefits on compatible trials (in which the prime and the target are mapped onto the same response) when appearing peripherally. In Experiment 1, the time course of this central-peripheral asymmetry (CPA) was investigated. For central primes, compatible-trial benefits at short stimulus onset asynchronies (SOAs) turned into incompatible-trial benefits at longer SOAs. For peripheral primes, compatible-trial benefits at short SOAs increased in size with longer SOAs. Experiment 2 showed that these effects also occur when primes and targets are physically dissimilar, ruling out an interpretation in terms of the perceptual properties of the stimulus material. In Experiments 3 and 4, the question was investigated as to whether the CPA is related to visual-spatial attention and/or retinal eccentricity per se. The results indicate that the CPA is independent of attentional factors but strongly related to the physiological inhomogeneity of the retina. It is argued that central and peripheral primes trigger an initial motor activation, which is inhibited only if primes are presented at retinal locations of sufficiently high perceptual sensitivity. The results are discussed in terms of an activation threshold model.

Adult↗
PubMed1992

Transvaginal ultrasonography.

Transvaginal ultrasonography has provided new anatomic and pathophysiologic information about the female pelvis. Because of probe proximity to the organ of interest and higher insonating frequency, resolution is dramatically improved. Problems previously encountered during transabdominal scanning, such as obesity, bowel gas, and a retroverted uterus, no longer preclude accurate diagnosis. Patient acceptance is nearly universal. Physiologic information concerning the endometrium and ovarian follicles has improved infertility diagnosis and treatment. Hormonal and vascular Doppler changes can be correlated with cyclic endometrial patterns and follicle size. Oocyte retrieval, management of pre-existing inflammatory disease, and treatment of complications of pregnancy are easier and safer with a transvaginal approach. Uterine malformations, leiomyomas, and cancers are more easily detected in premenopausal and postmenopausal women. The documentation of early intrauterine or ectopic pregnancy has decreased maternal morbidity and mortality. Tube-sparing procedures with preservation of reproductive potential are now more commonly employed due to earlier recognition of unruptured tubal pregnancy. Interventional TVS has led to improved recognition and treatment of pelvic cysts and abscesses and multiple pregnancy. Chorionic villous sampling can be performed more easily without the need for anesthesia, with adequate tissue obtained.

Female↗
PubMed1983

Spatio-temporal interaction in neurones of the cat's dorsal lateral geniculate nucleus.

Temporal contrast sensitivities in the range 0.33-42 Hz for optimum spatial frequency grating stimuli were measured for large populations of XG and YG neurones. For fewer cells, complete spatial contrast sensitivity profiles were measured at a series of temporal frequencies and, in some cases, at a range of levels of retinal illumination too. Contrast sensitivities were measured from responses of cells reliably different from their maintained discharges. The cells' discharges were recorded extracellularly from the binocular segment of the A laminae of the cat's dorsal lateral geniculate nucleus. At their respective optimum spatial frequencies, YG cell were more sensitive on average than XG cells for most temporal frequencies, though the average temporal contrast sensitivity profiles of both cell classes had similar shapes. The optimum temporal frequency for both cell types was around 5 Hz. XG and YG cells seem to be relatively less sensitive to low temporal frequencies than their ganglion cell counterparts. At a retinal illumination of 230 cd/m2 (pupil, 3 mm2), increasing temporal frequency in the range 0.65-21 Hz produced a relative improvement in low spatial frequency contrast sensitivity in most XG and all YG cells studied. There were some XG cells, though, which showed little or no effect of temporal frequency on their spatial contrast sensitivity curves. At all temporal frequencies, the shapes of spatial contrast sensitivity curves and the cells' temporal contrast sensitivity profiles were not markedly dependent on the criterion level set to measure 'threshold' contrast. Reducing the level of retinal illumination in the range 230-0.007 cd/m2 (pupil, 3 mm2) produced a fall in contrast sensitivities for both XG and YG cells. The loss in sensitivity was more marked at high spatial and high temporal frequencies. The similar shapes of the temporal contrast sensitivity curves of XG and YG cells weakens the suggestion that the human counterparts of these cells would provide a suitable physiological substrate for the psychophysical sustained and transient channels. Although the behaviour of XG and YG cells parallels quite closely changes in cat and human psychophysical spatial contrast sensitivities with temporal frequency and retinal illumination, many problems remain for equating results from the two fields.

Animals↗
PubMed1995

Posttranslational modifications of bovine osteopontin: identification of twenty-eight phosphorylation and three O-glycosylation sites.

Osteopontin (OPN) is a multiphosphorylated glycoprotein found in bone and other normal and malignant tissues, as well as in the physiological fluids urine and milk. The present study demonstrates that bovine milk osteopontin is phosphorylated at 27 serine residues and 1 threonine residue. Phosphoamino acids were identified by a combination of amino acid analysis, sequence analysis of S-ethylcysteine-derivatized phosphopeptides, and mass spectrometric analysis. Twenty-five phosphoserines and one phosphothreonine were located in Ser/Thr-X-Glu/Ser(P)/Asp motifs, and two phosphoserines were found in the sequence Ser-X-X-Glu/Ser(P). These sequence motifs are identical with the recognition sequences of mammary gland casein kinase and casein kinase II, respectively. Examination of the phosphorylation pattern revealed that the phosphorylations were clustered in groups of approximately three spanned by unphosphorylated regions of 11-32 amino acids. This pattern is probably of importance in the multiple functions of OPN involving interaction with Ca2+ and inorganic calcium salts. Furthermore, three O-glycosylated threonines (Thr 115, Thr 124, and Thr 129) have been identified in a threonine- and proline-rich region of the protein. Three putative N-glycosylation sites (Asn 63, Asn 85, and Asn 193) are present in bovine osteopontin, but sequence and mass spectrometric analysis showed that none of these asparagines were glycosylated in bovine mammary gland osteopontin. Alignment analysis showed that the majority of the phosphorylation sites in bovine osteopontin as well as all three O-glycosylation sites were conserved in other mammalian sequences. This conservation of serines, even in otherwise less well-conserved regions of the protein, indicates that the phosphorylation of osteopontin at specific sites is essential for the function of the protein.

Amino Acid Sequence↗
PubMedDate not supplied

A novel method for GPCR recognition and family classification from sequence alone using signatures derived from profile hidden Markov models.

G-protein coupled receptors (GPCRs) constitute a broad class of cell-surface receptors, including several functionally distinct families, that play a key role in cellular signalling and regulation of basic physiological processes. GPCRs are the focus of a significant amount of current pharmaceutical research since they interact with more than 50% of prescription drugs, whereas they still comprise the best potential targets for drug design. Taking into account the excess of data derived by genome sequencing projects, the use of computational tools for automated characterization of novel GPCRs is imperative. Typical computational strategies for identifying and classifying GPCRs involve sequence similarity searches (e.g. BLAST) coupled with pattern database analysis (e.g. PROSITE, BLOCKS). The diagnostic method presented here is based on a probabilistic approach that exploits highly discriminative profile Hidden Markov Models, excised from low entropy regions of multiple sequence alignments, to derive potent family signatures. For a given query, a P-value is obtained, combining individual hits derived from the same family. Hence a best-guess family membership is depicted, allowing GPCRs' classification at a family level, solely using primary structure information. A web-based version of the application is freely available at URL: http:/bioinformatics.biol.uoa.gr/PRED-GPCR.

Databases, Factual↗
PubMed2005

Motor-maps, navigation and implicit space representation in the hippocampus.

Multiple sensory-motor maps located in the brainstem and the cortex are involved in spatial orientation. Guiding movements of eyes, head, neck and arms they provide an approximately linear relation between target distance and motor response. This involves especially the superior colliculus in the brainstem and the parietal cortex. There, the natural frame of reference follows from the retinal representation of the environment. A model of navigation is presented that is based on the modulation of activity in those sensory-motor maps. The actual mechanism chosen was gain-field modulation, a process of multimodal integration that has been demonstrated in the parietal cortex and superior colliculus, and was implemented as attraction to visual cues (colour). Dependent on the metric of the sensory-motor map, the relative attraction to these cues implemented as gain field modulation and their position define a fixed point attractor on the plane for locomotive behaviour. The actual implementation used Kohonen-networks in a variant of reinforcement learning that are well suited to generate such topographically organized sensory-motor maps with roughly linear visuo-motor response characteristics. In the following, it was investigated how such an implicit coding of target positions by gain-field parameters might be represented in the hippocampus formation and under what conditions a direction-invariant space representation can arise from such retinotopic representations of multiple cues. Information about the orientation in the plane--as could be provided by head direction cells--appeared to be necessary for unambiguous space representation in our model in agreement with physiological experiments. With this information, Gauss-shaped "place-cells" could be generated, however, the representation of the spatial environment was repetitive and clustered and single cells were always tuned to the gain-field parameters as well.

Algorithms↗
PubMed1996

The rationale and utility of neurophysiological investigations in clinical monitoring for brain and spinal cord ischaemia during surgery and intensive care.

This review concerns the role of neurophysiological monitoring in prevention of damage to the brain or spinal cord from inadequate supply of oxygenated blood during surgery and intensive care. The spontaneous and evoked electrical activity from neurones depends on oxidative metabolism of glucose, the substrate being delivered via the arterial blood supply and not stored locally. In critical situations electrical activity declines as oxygen delivery fails. Since this happens before neuronal death occurs it can provide early warning of risk. Methods for signal processing of EEG for this purpose must include time domain assessment and recognition of burst suppression pattern, as well as frequency domain information, and provide multivariate pattern recognition. Models for monitoring systems require analysis of data sets based on clinical studies where accurate outcome data is available so that valid comparisons between different approaches can be made. Neurophysiological features must be considered in the context of other relevant clinical parameters in the design of effective warning systems for prevention of brain damage due to inadequate oxygen supply.

Brain Ischemia↗
PubMed2005

Single molecule studies of antibody-antigen interaction strength versus intra-molecular antigen stability.

We investigated molecular recognition of antibodies to membrane-antigens and extraction of the antigens out of membranes at the single molecule level. Using dynamic force microscopy imaging and enzyme immunoassay, binding of anti-sendai antibodies to sendai-epitopes genetically fused into bacteriorhodopsin molecules from purple membranes were detected under physiological conditions. The antibody/antigen interaction strength of 70-170 pN at loading rates of 2-50 nN/second yielded a barrier width of x = 0.12 nm and a kinetic off-rate (corresponding to the barrier height) of k(off) = 6s(-1), respectively. Bacteriorhodopsin unfolding revealed a characteristic intra-molecular force pattern, in which wild-type and sendai-bacteriorhodopsin molecules were clearly distinguishable in their length distributions, originating from the additional 13 amino acid residues epitope in sendai purple membranes. The inter-molecular antibody/antigen unbinding force was significantly lower than the force required to mechanically extract the binding epitope-containing helix pair out of the membrane and unfold it (126 pN compared to 204 pN at the same loading rate), meeting the expectation that inter-molecular unbinding forces are weaker than intra-molecular unfolding forces responsible for stabilizing native conformations of proteins.

Antibodies↗