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Biomedical subjects

C J James

Publications and source records attributed to C J James.

15 recordsLinked to original sources

Nitrite inhibits hydrogen production and kills the cattle parasite Tritrichomonas foetus.

AIMS: To investigate the effects of NaNO2 on the microaerophilic flagellated protozoan, Tritrichomonas foetus KV1, an economically important cattle parasite that inhabits the vagina and can spread rapidly through herds of animals by sexual transmission and leads to abortion of foetal calves. METHODS AND RESULTS: Growth of the parasite was inhibited by 50% in the presence of 4 mm NaNO2; immediate killing occurred at 10 mm. Mass spectrometric monitoring of gases showed that H2 and CO2 evolution were inhibited by NaNO2, and electron paramagnetic resonance spectrometry revealed a signal similar to that of a thiolate-iron-NO complex. Growth with sublethal concentrations of NaNO2 yielded organisms that produced ethanol rather than H2. CONCLUSIONS: NaNO2 probably inactivates FeS protein(s) of hydrogenosomes so as to inhibit the conversion of pyruvate (derived from maltose in the growth medium) to H2 and acetate. SIGNIFICANCE AND IMPACT OF THE STUDY: The use of NaNO2 as a topical antitrichomonal agent in veterinary practice is a possibility. At present, slaughter of infected animals is the favoured method of control.

Animals↗

The electroencephalogram through a software microscope: non-invasive localization and visualization of epileptic seizure activity from inside the brain.

OBJECTIVE: We developed a novel non-invasive analysis to localize the source and visualize the time course of electrical activity generated inside the brain but unclear from the scalp. This analysis applies to signals with unique waveform characteristics, such as seizures. METHODS: The method extracts activity from an EEG data matrix as a spatiotemporal component having waveforms uncorrelated to the other concurrent activities. The method also provides the location and orientation of the dipole generating this activity. We applied this method to ten scalp seizures in three patients with temporal lobe epilepsy and single-focus seizures confirmed by intracerebral recordings. A realistic head model based on MRI was used for computation of field distributions. RESULTS: When seizure activity was still not visually identifiable on the scalp, the method demonstrated in all scalp seizures a source in the temporal neocortex corresponding clearly to the region of seizure activity in intracerebral recordings. Frequency characteristics of the estimated activities also resembled those of the intracerebral seizures. CONCLUSIONS: This method enables estimation of focal brain activity when its effect on scalp EEG is unclear to visual examination. It works in situations where currently available source analyses methods, which require noiseless definite activity, are not applicable.

Brain↗

Using weighted linear spatial decomposition to investigate brain activity through a set of fixed current dipoles.

OBJECTIVES: We developed a method with the aim of decorrelating scalp EEG based on a set of spatial constraints. METHODS: We assume that the scalp EEG can be modelled by a small number of current dipoles of fixed location and orientation, placed at regions of interest. The algorithm is based on weighted linear spatial decomposition in order to obtain a weighted solution to the inverse problem. An EEG data matrix is first weighted in favour of a single dipole in the set. The dipole moment is then calculated from the weighted EEG by the pseudo-inverse method. This is repeated for each dipole. RESULTS: Six seizures were processed from 4 patients using the standard least-squares solution and our weighted version. The average cross-correlation between channels was calculated for each case. The first method resulted in a mean drop in cross-correlation of 16.5% from that of the scalp. Our method resulted in a reduction of 34.5%. CONCLUSIONS: Our method gives a more spatially decorrelated signal in regions of interest (although it is not intended as an accurate localization tool). Subsequent analysis is more robust and less likely to be dependent on specific recording montages. This is more than could be obtained using a standard least-squares solution using the same model.

Brain↗

Monaural and binaural loudness measures in cochlear implant users with contralateral residual hearing.

OBJECTIVE: The aim was to measure the loudness of monaural and binaural stimuli in a group of cochlear implant users who had residual hearing in the nonimplanted ear, and to consider the implications of these measures for a binaural fitting consisting of a hearing aid and an implant in opposite ears. Three independent hypotheses were addressed: that the shapes of the electric and acoustic loudness growth functions would be similar, although the dynamic ranges would differ; that standard implant and hearing aid fittings would result in substantial loudness mismatches between the acoustic and electric signals; and that loudness summation would occur for binaural combinations of electric and acoustic signals. DESIGN: A modified version of the "Loudness Growth in 1/2-Octave Bands" method (Allen, Hall, & Jeng, 1990) was used to measure loudness growth for each ear of nine subjects. At the time of the experiment, the subject group included all implant users in Melbourne and Denver who were available for research and who also had sufficient residual hearing to use a hearing aid in the nonimplanted ear. Five acoustic frequencies and five electrodes were measured for each subject. The same subjects also estimated the loudness of a set of stimuli including monaural and binaural signals chosen to cover the loudness range from very soft to loud. RESULTS: The shapes of the averaged loudness growth functions were similar in impaired and electrically stimulated ears, although the shapes of iso-loudness curves were quite different in the two ears, and dynamic ranges varied considerably. Calculations based on the psychophysical data demonstrated that standard fitting procedures for cochlear implants and hearing aids lead to a complex pattern of loudness differences between the ears. A substantial amount of loudness summation was observed for the binaural stimuli, with most summation occurring when the acoustic and electric components were of equal loudness. This is consistent with observations for subjects with normal hearing and subjects with bilaterally impaired hearing. CONCLUSIONS: These experiments provide data on which criteria and methods for the binaural fitting of cochlear implants and hearing aids may be based. It is unlikely that standard monaural fitting methods for cochlear implants and hearing aids will result in balanced loudness between the two ears across a reasonably broad range of frequencies and levels. It is also likely that output levels of both devices will need to be reduced relative to a monaural fitting to compensate for the binaural summation of loudness in some listeners.

Adult↗

Effect of current level on electrode discrimination in electrical stimulation.

The effect of the stimulation intensity (current amplitude) on the ability to discriminate electrodes was tested in an experiment with four adult users of the Nucleus-22 cochlear implant. A total of 12 adjacent pairs of electrodes were used in the four-interval forced-choice discrimination task with random current variation. Tests were carried out at three average stimulation levels: 40 and 70% of the dynamic range and close to maximum comfortable loudness. Analysis of variance revealed a significant (P<0.0001) deterioration in electrode discrimination with a decreasing level. However, the overall effect was very small, representing a deterioration in the discrimination score of only 18% correct from the highest to lowest levels tested. The reason for the small deterioration in discriminability with a decreasing level is difficult to determine from this experiment, however, the results are consistent with the hypothesis that changes in the 'peak' or 'edge' of the excitation pattern are more important for discrimination tasks than the relative amount of non-overlap of the excitation areas from the two electrodes.

Analysis of Variance↗

Isolation of epileptiform discharges from unaveraged EEG by independent component analysis.

OBJECTIVE: We propose a method that allows the separation of epileptiform discharges (EDs) from the EEG background, including the ED's waveform and spatial distribution. The method even allows to separate a spike in two components occurring at approximately the same time but having different waveforms and spatial distributions. METHODS: The separation employs independent component analysis (ICA) and is not based on any assumption regarding generator model. A simulation study was performed by generating ten EEG data matrices by computer: each matrix included real background activity from a normal subject to which was added an array of simulated unaveraged EDs. Each discharge was a summation of two transients having slightly different potential field distributions and small jitters in time and amplitude. Real EEG data were also obtained from three epileptic patients. RESULTS: Through ICA, we could isolate the two epileptiform transients in every simulation matrix, and the retrieved transients were almost identical as the originals, especially in their spatial distributions. Two epileptic components were isolated by ICA in all patients. Each estimated epileptic component had a consistent time course. CONCLUSION: ICA appears promising for the separation of unaveraged spikes from the EEG background and their decomposition in independent spatio-temporal components.

Algorithms↗

Detection of epileptiform discharges in the EEG by a hybrid system comprising mimetic, self-organized artificial neural network, and fuzzy logic stages.

OBJECTIVE: A multi-stage system for automated detection of epileptiform activity in the EEG has been developed and tested on pre-recorded data from 43 patients. METHODS: The system is centred on the use of an artificial neural network, known as the self-organising feature map (SOFM), as a novel pattern classifier. The role of the SOFM is to assign a probability value to incoming candidate epileptiform discharges (on a single channel basis). The multi-stage detection system consists of three major stages: mimetic, SOFM, and fuzzy logic. Fuzzy logic is introduced in order to incorporate spatial contextual information in the detection process. Through fuzzy logic it has been possible to develop an approximate model of the spatial reasoning performed by the electroencephalographer. RESULTS: The system was trained on 35 epileptiform EEGs containing over 3000 epileptiform events and tested on a different set of eight EEGs containing 190 epileptiform events (including one normal EEG). Results show that the system has a sensitivity of 55.3% and a selectivity of 82% with a false detection rate of just over seven per hour. CONCLUSIONS: Based on these initial results the overall performance is favourable when compared with other leading systems in the literature. This encourages us to further test the system on a larger population base with the ultimate aim of introducing it into routine clinical use.

Adult↗

Early developmental destruction of terminals in the striatal target induces apoptosis in dopamine neurons of the substantia nigra.

Many developing neural systems with peripheral projections depend on their target for trophic support during a critical period of natural cell death. Much less is known about central systems. That dopaminergic neurons of the substantia nigra may depend on their target, the striatum, during development is suggested by the presence of a natural apoptotic cell death event in these neurons that can be augmented by an early developmental axon-sparing striatal injury. To further assess the target dependence of these neurons, we have used the selective neurotoxin 6-hydroxydopamine to lesion their terminals within the striatum during development, while sparing intrinsic striatal target neurons. This lesion results in an induction of apoptotic cell death in phenotypically defined dopaminergic neurons that appears on the third postlesion day and persists until the tenth. This inducibility of cell death is dependent on developmental age: it is most marked before postnatal day (PND) 14. As late as PND42, inducibility is still detectable but much less so. In addition, at day 42 the morphology of cell death changes and becomes nonapoptotic in some cells. We conclude that terminal injury during a critical period of postnatal development, like axon-sparing target injury, induces augmented apoptotic death in mesencephalic dopaminergic neurons. These results suggest that these neurons have a period of target dependence. Regulation of this dependence is likely to influence the mature adult number of dopaminergic neurons.

Animals↗

Multireference adaptive noise canceling applied to the EEG.

The technique of multireference adaptive noise canceling (MRANC) is applied to enhance transient nonstationarities in the electroeancephalogram (EEG), with the adaptation implemented by means of a multilayer-perception artificial neural network (ANN). The method was applied to recorded EEG segments and the performance on documented nonstationarities recorded. The results show that the neural network (nonlinear) gives an improvement in performance (i.e., signal-to-noise ratio (SNR) of the nonstationarities) compared to a linear implementation of MRANC. In both cases an improvement in the SNR was obtained. The advantage of the spatial filtering aspect of MRANC is highlighted when the performance of MRANC is compared to that of the inverse auto-regressive filtering of the EEG, a purely temporal filter.

Algorithms↗

Mutations in phosphofructokinases alter the control characteristics of glycolysis in vivo in Saccharomyces cerevisiae.

Ethanol and CO2 production from glucose by non-proliferating suspensions of aerobically-grown, glucose-derepressed wild-type Saccharomyces cerevisiae is inhibited by O2; monitoring by mass spectrometry provides a direct method for measurement of the Pasteur effect. Under aerobic conditions, that part of the CO2 evolved equivalent to the O2 consumed, is produced by respiration: subtraction of this respiratory CO2 from the total gives CO2 produced by aerobic glycolysis. Pasteur quotients (anaerobic CO2/aerobic glycolytic CO2) were within the range 1.2 to 3.0. The Pasteur effect was not observed in the presence of carbonyl cyanide m-chlorophenylhydrazone, an uncoupler of mitochondrial energy metabolism, or in a rho degree cytoplasmic petite mutant. A 'non-allosteric' mutant with an altered regulatory subunit of phosphofructokinase showed no Pasteur effect. Strains bearing a nonsense mutation pfk1 in the catalytic subunit of soluble phosphofructokinase (PFKI) also showed no Pasteur effect; the residual fermentative activity of this strain was dependent on PFKII, the particulate phosphofructokinase. A double mutant lacking both PFKI and glucose-6-phosphate dehydrogenase showed similar characteristics to those of the single pfk1 mutant; this indicates that the hexose monophosphate shunt is not acting to bypass the phosphofructokinase block. A 'hyper-allosteric' mutant altered in the regulatory subunit encoded by the gene PFK2 showed characteristics of glucose fermentation and ethanol oxidation very similar to those of wild-type organisms. These results indicate that either of the two phosphofructokinases can carry out glycolysis.

Aerobiosis↗

Speech audiometry: digitization effects and the non-equivalence of isophonemic word lists.

Phonetically balanced word lists have many applications, including the field of audiometric testing, as equivalent test material. An experiment designed to assess the effects of digitizing parameters on speech intelligibility has shown, following detailed analysis, that the lists show a degree of non-equivalence. The reasons for this are explored and questions asked about the fundamental principles involved in describing speech forms. Other approaches to this kind of assessment are discussed.

Adult↗

Facilitated light microscopic cytochemical diagnosis of acute myelogenous leukemia.

Hydroperoxidase-positive Phi bodies and rods are much more prominent and prevalent than rods visualized with a Romanovsky-type stain (Auer rods) in immature leukocytes of patients with active acute myelogenous leukemia (AML). They are readily observed with the light microscope in peripheral blood or marrow films of AML patients stained to show their peroxidatic activity. In many of these patients, Auer rods, which apparently constitute only a small subpopulation of the hydroperoxidase-positive Phi bodies and rods, were detected with difficulty, if at all. The hydroperoxidase-positive Phi bodies and rods were observed in 92% of 36 patients with active disease. They were never observed in leukocytes of patients with other hematopoietic disorders or of normal individuals. Thus, they facilitated the distinction of AML from acute lymphocytic leukemia and chronic granulocytic leukemia in blast crisis. They were absent in full clinical remission after chemotherapy and were greatly diminished in partial remission. They were present in disease relapse and reappeared in five patients who had been in full remission. These results suggest that these hydroperoxidase-positive enlarged particles are pathognomonic of AML and that monitoring them with the light microscope may aid in guiding its clinical management.

Adolescent↗