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Biomedical subjects

A C James

Publications and source records attributed to A C James.

At least 19 recordsLinked to original sources
PubMed2003

USTUR case 0259 whole body donation: a comprehensive test of the current ICRP models for the behavior of inhaled 238PuO2 ceramic particles. U.S. Transuranium and Uranium Registries.

An analysis of 238Pu in the whole body donation to the U.S. Transuranium and Uranium Registries (USTUR) is presented. This donor accidentally inhaled an unusual physical form of plutonium, predominantly the 238Pu isotope in the form of a highly insoluble ceramic. Along with six other workers accidentally exposed at the same time, this donor excreted little or no 238Pu in his urine for several months. Subsequently, however, and, with no further intakes, the urinary excretion of 238Pu by all of these workers increased progressively. Such a pattern of increasing urinary excretion of plutonium resulting from a single acute inhalation was unknown at the time. The subject of this study provided a unique opportunity to analyze not only the pattern of urinary excretion for 17 y following this unusual intake but also the complete distribution of 238Pu in his donated body tissues and skeleton at death. Radiochemical analyses of tissues from this whole body donation were used to perform critical tests of the applicability and accuracy of the respiratory tract model and the systemic biokinetic models for plutonium currently recommended by the International Commission on Radiological Protection. The respiratory tract model was applied to analyze the donor's long-term urinary excretion pattern. The facility provided by this model to represent progressive transformation of insoluble particles in the lungs into a more soluble form, applied in conjunction with the systemic biokinetic model, predicted the total amount of 238Pu measured in the donor's body to within 17% accuracy. The measured division of 238Pu between the donor's lungs and systemic organs was predicted to within 10%. Small adjustments to several rate constants in these models provided precise predictions of the absolute amounts of 238Pu in the lungs, thoracic lymph nodes, liver, red bone marrow, skeleton (including the distribution of 238Pu between trabecular and cortical bone matrices derived from the radiochemical analyses), kidneys, testes, and muscle. The resulting individual-specific parameters were applied to evaluate the equivalent dose rates and cumulative doses received by the donor's organs and the overall effective dose. Whereas these individual modifications to the ICRP models provided a more accurate representation of the distribution of dose between the donor's organs, it was determined that the ICRP models provided an adequate estimate of the overall effective dose.

Air Pollution, Radioactive↗
PubMed2002

Dynamics of double and single Wolbachia infections in Drosophila simulans from New Caledonia.

The bacterial symbiont Wolbachia can cause cytoplasmic incompatibility in Drosophila simulans flies: if an infected male mates with an uninfected female, or a female with a different strain of Wolbachia, there can be a dramatic reduction in the number of viable eggs produced. Here we explore the dynamics associated with double and single Wolbachia infections in New Caledonia. Doubly infected females were compatible with all males in the population, explaining the high proportion of doubly infected flies. In this study, males that carry only wHa or wNo infections showed reduced incompatibility when mated to uninfected females, compared with previous reports. These data suggest that either the DNA of these bacterial isolates have diverged from those previously collected, or the genetic background of the host has lead to a reduction in the phenotype of incompatibility. Mitochondrial sequence polymorphism at two sites within the host genome was assayed to investigate population structure related to infection types. There was no correlation between sequence polymorphism and infection type suggesting that double infections are the stable type, with singly infected and uninfected flies arising from stochastic segregation of bacterial strains. Finally, we discuss the nomenclature of Wolbachia strain designation.

Animals↗
PubMed2001

Enlargement of the fornix in early-onset schizophrenia: a quantitative MRI study.

Abnormalities of temporal lobe structure and frontal lobe function occur in schizophrenia. There have been few studies of young people with schizophrenia and little is known about temporo-frontal connectivity in the disease. Therefore, the cross-sectional area of the body of the fornix was measured on MR images from 17 young people with schizophrenia, nine with other serious psychiatric illnesses and eight without illness. The mean age of each group was 16-17 years. The mean cross-sectional fornix area in subjects with schizophrenia was significantly larger than that in subjects without illness ( approximately 40%) and psychiatric controls ( approximately 26%). There was no such significant difference between subjects without illness and psychiatric controls. The nature of the larger fornix in early-onset schizophrenia, whether it persists and whether it occurs in schizophrenia presenting in adulthood, remain to be elucidated.

Adolescent↗
PubMed2001

The role of feedback connections in shaping the responses of visual cortical neurons.

The results of a previous study [Hupé et al. (1998) Nature, 394: 784-787] led us to conclude that feedback connections are important for differentiating a figure from the background, particularly in the case of low salience stimuli. This conclusion was principally based on the observation in area V3 neurons that inactivating MT by cooling led to a severe weakening of the center response and of the center-surround interactions, and that these effects were particularly strong for low salience stimuli. In the present paper, we first show that the results extend to areas V1 and V2. In particular, the inhibitory center-surround interactions in areas V1, V2 and V3 disappear almost completely in the absence of feedback input from MT for low salience stimuli, whereas the effects are much more limited for stimuli of middle and high salience. We then compare the results obtained in studies of feedback connections from MT to those obtained in a study of the feedback action of area V2 onto V1 neurons [Hupé et al. (2001) J. Neurophysiol., 85: 146-163], in which the same effects were observed on the center mechanism (decrease in response), but no effects were seen on the center-surround interactions. We conclude that feedback connections act in a non-linear fashion to boost the gain of the center mechanism and that they combine with horizontal connections to generate the center-surround interactions.

Animals↗
PubMed2001

Feedback connections act on the early part of the responses in monkey visual cortex.

We previously showed that feedback connections from MT play a role in figure/ground segmentation. Figure/ground coding has been described at the V1 level in the late part of the neuronal responses to visual stimuli, and it has been suggested that these late modulations depend on feedback connections. In the present work we tested whether it actually takes time for this information to be fed back to lower order areas. We analyzed the extracellular responses of 169 V1, V2, and V3 neurons that we recorded in two anesthetized macaque monkeys. MT was inactivated by cooling. We studied the time course of the responses of the neurons that were significantly affected by the inactivation of MT to see whether the effects were delayed relative to the onset of the response. We first measured the time course of the feedback influences from MT on V1, V2, and V3 neurons tested with moving stimuli. For the large majority of the 51 neurons for which the response decreased, the effect was present from the beginning of the response. In the responses averaged after normalization, the decrease of response was significant in the first 10-ms bin of response. A similar result was found for six neurons for which the response significantly increased when MT was inactivated. We then looked at the time course of the responses to flashed stimuli (95 neurons). We observed 15 significant decreases of response and 14 significant increases. In both populations, the effects were significant within the first 10 ms of response. For some neurons with increased responses we even observed a shorter latency when MT was inactivated. We measured the latency of the response to the flashed stimuli. We found that even the earliest responding neurons were affected early by the feedback from MT. This was true for the response to flashed and to moving stimuli. These results show that feedback connections are recruited very early for the treatment of visual information. It further indicates that the presence or absence of feedback effects cannot be deduced from the time course of the response modulations.

Animals↗
PubMed2001

Response modulations by static texture surround in area V1 of the macaque monkey do not depend on feedback connections from V2.

We analyzed the extracellular responses of 70 V1 neurons (recorded in 3 anesthetized macaque monkeys) to a single oriented line segment (or bar) placed within the cell classical receptive field (RF), or center of the RF. These responses could be modulated when rings of bars were placed entirely outside, but around the RF (the "near" surround region), as described in previous studies. Suppression was the main effect. The response was enhanced for 12 neurons when orthogonal bars in the surround were presented instead of bars having the same orientation as the center bar. This orientation contrast property is possibly involved in the mediation of perceptual pop-out. The enhancement was delayed compared with the onset of the response by about 40 ms. We also observed a suppression originating specifically from the flanks of the surround. This "side-inhibition," significant for nine neurons, was delayed by about 20 ms. We tested whether these center/surround interactions in V1 depend on feedback connections from area V2. V2 was inactivated by GABA injections. We used devices made of six micropipettes to inactivate the convergent zone from V2 to V1. We could reliably inactivate a 2- to 4-mm-wide region of V2. Inactivation of V2 had no effect on the center/surround interactions of V1 neurons, even those that were delayed. Therefore the center/surround interactions of V1 neurons that might be involved in pop-out do not appear to depend on feedback connections from V2, at least in the anesthetized monkey. We conclude that these properties are probably shaped by long-range connections within V1 or depend on other feedback connections. The main effect of V2 inactivation was a decrease of the response to the single bar for about 10% of V1 neurons. The decrease was delayed by <20 ms after the response onset. Even the earliest neurons to respond could be affected by the feedback from V2. Together with the results on feedback connections from MT (previous paper), these findings show that feedback connections potentiate the responses to stimulation of the RF center and are recruited very early for the treatment of visual information.

Anesthesia↗
PubMed2001

The treatment of bipolar disorder in children and adolescents.

This paper reviews the presentation, clinical features. and management of early-onset bipolar disorder. A framework for the treatment is based upon a systematic, critical appraisal of the available literature. A multimodal approach is emphasised using individual and family psychoeducational interventions in conjunction with pharmacotherapy. The role of mood stabilisers--lithium--and the anticonvulsants--sodium valproate and carbamazepine is reviewed, alongside the treatments for depression in bipolar disorder and refractory mania.

Adolescent↗
PubMed2000

Development of functional connections between thalamic fibres and the visual cortex of the wallaby revealed by current source density analysis in vivo.

Functional development of thalamic input to the cortex in anaesthetised wallaby pouch young between postnatal day 25 (P25) and P153 has been studied by electrical stimulation of the optic nerve, current source density (CSD) analysis, and histologic identification of recording sites. Conduction in the optic nerve was recorded prior to P39, by which time responses from the superior colliculus appeared. No evoked potential of cortical origin was recorded until P46, even though thalamic fibres grew into the cortical plate from P15. The first cortical synaptic responses were recorded at the margin of the subplate and the developing cortical plate, where cells that later comprise the adult layer 6 settle. At about P66, an additional short-latency, superficial response appeared, coinciding with the formation of layer 4. The deep response was retained in layer 6. Evoked activity in the presumed layer 4 was found progressively deeper in the cortex over the next few weeks, which would be expected from the addition of layer 3 above it. By P113, a new sink was added superficial in the cortex. Thalamocortical connections follow the same deep-to-superficial order in development as the cellular layers of the cortex.

Animals↗
PubMed2000

Cellular basis of wing size variation in Drosophila melanogaster: a comparison of latitudinal clines on two continents.

We investigated the cellular basis of two extensive, continuous, latitudinal, genetic, body size clines of Drosophila melanogaster by measuring wing area and cell size in the wing blade of adult flies reared under standard, laboratory conditions. We report that the contribution of cell size to an Australian cline is much smaller than that to a South American cline. The data suggest that neither cell size nor cell number were the targets of selection, but rather wing area itself, or a trait closely related to it. We hypothesize that the differences between the continents were caused by differences in the initial pattern of genetic variation for the cell traits and/or by the direction of selection on the source populations of the clines. Despite large differences between continents in the cellular basis of the latitudinal variation, multiple regression analysis, using the individual variation within populations, showed that the relationship between cell size and cell number was changed with latitude in the same way in the two clines. The relative contribution of cell number to wing area variation increased with latitude, probably because of compensatory interactions with cell size as a consequence of the latitudinal increase in cell number. Our findings are discussed in relation to the cellular basis of evolutionary change in laboratory thermal selection lines and natural populations along latitudinal clines.

Analysis of Variance↗
PubMed2000

Expression of cytoplasmic incompatibility in Drosophila simulans and its impact on infection frequencies and distribution of Wolbachia pipientis.

The aim of this study is to examine the expression of cytoplasmic incompatibility and investigate the distribution and population frequencies of Wolbachia pipientis strains in Drosophila simulans. Nucleotide sequence data from 16S rDNA and a Wolbachia surface protein coding sequence and cytoplasmic incompatibility assays identify four distinct Wolbachia strains: wHa, wRi, wMa, and wAu. The levels of cytoplasmic incompatibility between six lines carrying these strains of bacteria and three control lines without bacteria are characterized. Flies infected with wHa and wRi are bidirectionally incompatible, and males that carry either strain can only successfully produce normal numbers of offspring with females carrying the same bacterial strain. Males infected with wAu do not express incompatibility. Males infected with the wMa strain express intermediate incompatibility when mated to females with no bacteria and no incompatibility with females with any other Wolbachia strain. We conduct polymerase chain reaction/restriction fragment length polymorphism assays to distinguish the strain of Wolbachia and the mitochondrial haplotype to survey populations for each type and associations between them. Drosophila simulans is known to have three major mitochondrial haplotypes (siI, sill, and siIII) and two subtypes (siIIA and siIIB). All infected lines of the sil haplotype carry wHa, wNo, or both; wMa and wNo are closely related and it is not clear whether they are distinct strains or variants of the same strain. Infected lines with the silIA haplotype harbor wRi and the siIIB haplotype carries wAu. The wMa infection is found in siIII haplotype lines. The phenotypic expression of cytoplasmic incompatibility and its relation to between-population differences in frequencies of Wolbachia infection are discussed.

Animals↗
PubMed2000

A spatial frequency-doubling illusion-based pattern electroretinogram for glaucoma.

PURPOSE: A pattern electroretinogram (PERG) in which stimuli displaying the frequency-doubling (FD) illusion are presented simultaneously to multiple parts of the visual field was evaluated for its ability to diagnose glaucoma. This multiregion FD PERG is referred to in the current study as the MFP. METHODS: The nine stimulus regions were temporally modulated at incommensurate frequencies typically producing an FD percept. Two other spatial scales of the stimuli were also investigated. The sensitivity and specificity of MFP were examined using linear and quadratic discriminant methods. RESULTS: Even with the simpler linear discriminant classification, sensitivities and specificities of 100% were obtained in eyes with moderate to severe glaucoma. Of eyes with glaucoma strongly suspected, 67% were classified as being glaucomatous. Stimulus patterns having differing spatial scales produced different PERG visual field dependencies. CONCLUSIONS: The differing results for the 16-fold change in spatial scale may reflect the accessing of different mechanisms. The MFP method appears to have significant value for the diagnosis of glaucoma.

Electroretinography↗
PubMed2000

Comparing a parallel PERG, automated perimetry, and frequency-doubling thresholds.

PURPOSE: A pattern electroretinogram (PERG) simultaneously displaying the frequency-doubling (FD) illusion in nine parts of the visual field was compared with two other methods for ability to detect glaucoma. This multiregion FD PERG (MFP) was compared with results from achromatic automated perimetry and psychophysical tests using FD stimuli. METHODS: MFP data were compared with that from the Humphrey Field Analyser (HFA; Humphrey, San Leandro, CA) 24-2 program. Contrast thresholds were also determined in different visual field locations for FD stimuli. Thin-plate spline methods were used to derive comparisons from the tests, each of which sampled the visual field differently. RESULTS: Significant correlation with HFA could be obtained, providing seven to nine (of nine) MFP amplitudes were themselves significant. Evidence showed that both the psychophysical tests using FD stimuli and the MFP detect glaucomatous damage not detected by the HFA. CONCLUSIONS: The comparisons between HFA perimetry, the MFP, and FD thresholds indicate that both FD-based tests quantify a form of diffuse loss in early glaucoma as well as the scotomas of later glaucoma.

Electroretinography↗
PubMed1999

Is the course of brain development in schizophrenia delayed? Evidence from onsets in adolescence.

A degree of ventricular enlargement, together with a reduction of total cortical mass and loss of asymmetry is reported in schizophrenia, but the meaning is obscure. These changes may reflect an anomaly of brain development. Brain structure was assessed on a 1.5-Tesla MRI scan in a series of 29 adolescents at the time of a first episode of schizophrenia and compared with 15 adolescents with other serious psychiatric disturbance (mostly psychotic) and 20 normal adolescent controls. The age at scan ranged between 13 and 20 years. In the adolescents with a diagnosis of schizophrenia, total brain volume increased with age in a way that differed significantly (p=0.007) from that seen in patients with other psychiatric disturbance and normal controls. Thus, brain growth, as assessed by this index, had reached a plateau in the control group by the age of 13 years, but this was not true of patients with schizophrenia. The measure that most clearly distinguished the groups (p<0.001 after co-varying for height and sex) was the volume of the left lateral ventricle the ventricle was significantly larger in patients with schizophrenic illness, and ventricular size increased with age to a greater extent in the patient group, although not significantly so, than in normal controls. Thus, aspects of brain growth are delayed in patients with early onset schizophrenia, and the greatest severity of illness is reflected in a component of growth that is lateralized to the dominant hemisphere. Individuals who develop serious psychiatric illness, including schizophrenia, represent a fraction of the population in whom a component of the relative development of the cerebral hemispheres occurs late.

Adolescent↗
PubMed1999

Testing for glaucoma with the spatial frequency doubling illusion.

We examined the performance of tests for glaucoma based on the spatial frequency doubling (FD) illusion. Contrast thresholds for seeing the FD illusion in four large visual field regions were measured from 340 subjects who were tested up to seven times over 2 years. Median sensitivities of 91% at specificities of 95% were obtained. Test-retest variability for the worst hemifield thresholds averaged 2.22 db +/- 0.09 S.E. for all tested groups, and significant progression was observed for glaucoma suspects over the seven visits, indicating that tests based on the FD illusion can detect diffuse early glaucomatous loss.

Adult↗
PubMed1999

Distribution of exposure concentrations and doses for constituents of environmental tobacco smoke.

The ultimate goal of the research reported in this series of three articles is to derive distributions of doses of selected environmental tobacco smoke (ETS)-related chemicals for nonsmoking workers. This analysis uses data from the 16-City Study collected with personal monitors over the course of one workday in workplaces where smoking occurred. In this article, we describe distributions of ETS chemical concentrations and the characteristics of those distributions (e.g., whether the distribution was log normal for a given constituent) for the workplace exposure. Next, we present population parameters relevant for estimating dose distributions and the methods used for estimating those dose distributions. Finally, we derive distributions of doses of selected ETS-related constituents obtained in the workplace for people in smoking work environments. Estimating dose distributions provided information beyond the usual point estimate of dose and showed that the preponderance of individuals exposed to ETS in the workplace were exposed at the low end of the dose distribution curve. The results of this analysis include estimations of hourly maxima and time-weighted average (TWA) doses of nicotine from workplace exposures to ETS (extrapolated from 1 day to 1 week) and doses derived from modeled lung burdens of ultraviolet-absorbing particulate matter (UVPM) and solanesol resulting from workplace exposures to ETS (extrapolated from 1 day to 1 year).

Absorption↗
PubMed1999

Cross-correlation study of the temporal interactions between areas V1 and V2 of the macaque monkey.

Cross-correlation studies performed in cat visual cortex have shown that neurons in different cortical areas of the same hemisphere or in corresponding areas of opposite hemispheres tend to synchronize their activities. The presence of synchronization may be related to the parallel organization of the cat visual system, in which different cortical areas can be activated in parallel from the lateral geniculate nucleus. We wanted to determine whether interareal synchronization of firing can also be observed in the monkey, in which cortical areas are thought to be organized in a hierarchy spanning different levels. Cross-correlation histograms (CCHs) were calculated from pairs of single or pairs of multiunit activities simultaneously recorded in areas V1 and V2 of paralyzed and anesthetized macaque monkeys. Moving bars and flashed bars were used as stimuli. The shift predictor was calculated and subtracted from the raw CCH to reveal interactions of neuronal origin in isolation. Significant CCH peaks, indicating interactions of neuronal origin, were obtained in 11% of the dual single-unit recordings and 46% of the dual multiunit recordings with moving bars. The incidence of nonflat CCHs with flashed bars was 29 and 78%, respectively. For the pairs of recording sites where both flashed and moving stimuli were used, the incidences of significant CCHs were very similar. Three types of peaks were distinguished on the basis of their width at half-height: T (<16 ms), C (between 16 and 180 ms), and H peaks (>180 ms). T peaks were very rarely observed (<1% in single-unit recordings). H peaks were observed in 7-16% of the single-unit CCHs, and C peaks in 6-16%, depending on the stimulus used. C and H peaks were observed more often when the receptive fields were overlapping or distant by <2 degrees. To test for the presence of synchronization between neurons in areas V1 and V2, we measured the position of the CCH peak with respect to the origin of the time axis of the CCH. Only in the case of a few T peaks did we find displaced peaks, indicating a possible drive of the V2 neuron by the simultaneously recorded V1 cell. All the other peaks were either centered on the origin or overlapped the origin of time with their upper halves. Thus similarly to what has been reported for the cat, neurons belonging to different cortical areas in the monkey tend to synchronize the time of emission of their action potentials with three different levels of temporal precision. For peaks calculated from flashed stimuli, we compared the peak position with the difference between latencies of V1 and V2 neurons. There was a clear correlation for single-unit pairs in the case of C peaks. Thus the position of a C peak on the time axis appears to reflect the order of visual activation of the correlated neurons. The coupling strength for H peaks was smaller during visual drive compared with spontaneous activity. On the contrary, C peaks were seen more often and were stronger during visual stimulation than during spontaneous activity. This suggests that C-type synchronization is associated with the processing of visual information. The origin of synchronized activity in a serially organized system is discussed.

Animals↗
PubMed1998

Cortical feedback improves discrimination between figure and background by V1, V2 and V3 neurons.

A single visual stimulus activates neurons in many different cortical areas. A major challenge in cortical physiology is to understand how the neural activity in these numerous active zones leads to a unified percept of the visual scene. The anatomical basis for these interactions is the dense network of connections that link the visual areas. Within this network, feedforward connections transmit signals from lower-order areas such as V1 or V2 to higher-order areas. In addition, there is a dense web of feedback connections which, despite their anatomical prominence, remain functionally mysterious. Here we show, using reversible inactivation of a higher-order area (monkey area V5/MT), that feedback connections serve to amplify and focus activity of neurons in lower-order areas, and that they are important in the differentiation of figure from ground, particularly in the case of stimuli of low visibility. More specifically, we show that feedback connections facilitate responses to objects moving within the classical receptive field; enhance suppression evoked by background stimuli in the surrounding region; and have the strongest effects for stimuli of low salience.

Animals↗