Biomedical subjects

Kevin A Johnson

Publications and source records attributed to Kevin A Johnson.

11 recordsLinked to original sources

PubMed2005

Metal accumulation in eggs of the red-eared slider (Trachemys scripta elegans) in the Lower Illinois River.

The Illinois River is a highly utilized navigable waterway in the US Midwest, and has historically been contaminated with metal toxicants from various industrial and municipal pollution sources. Little information on metal contamination is available in the Lower Illinois River, and in particular, in the habitat of the red-eared slider (Trachemys scripta elegans) at the southern end of the river near Grafton, IL. This study was conducted to determine current levels of metal contamination in water, sediment, soil, and plants in the habitat, as well as to reveal temporal and spatial variations of metal accumulation in eggs of the red-eared slider. Aluminum, Cd, Cr, Cu, Mn, Ni, Pb, V, Sn, and Zn were analyzed by inductively-coupled plasma spectroscopy. High concentrations of metals were observed in lake sediment, compared with the concentrations in water, soil, and plant tissues. Sediment Ni concentrations (mg kg(-1)) varied from 66 to 95 and Sn from 1100 to 1600. Five detectable metals in egg content were Zn (24.2 +/- 13), Al (2.2 +/- 1.2), Sn (1.8 +/- 1.1), Mn (1.1 +/- 0.6), and Cu (0.9 +/- 0.5); nine detectable metals in egg shell were Zn (6.8 +/- 3.9), Sn (3.7 +/- 3.1), Cu (1.9 +/- 1.3), Cr (1.6 +/- 1.5), V (1.6 +/- 1.4), Pb (1.3 +/- 0.7), Ni (1.3 +/- 0.9), Mn (1.0 +/- 0.8), and Cd (0.16 +/- 0.11). Zinc accumulation in egg content was significantly correlated with Zn in egg shell (r = 0.445, P < 0.002, n = 42). While significant spatial variation was observed in egg shell, metal accumulation in eggs (content and shell) collected from the same ground of turtles consecutively for 4 years did not show a significant temporal change.

Animals↗

PubMed2005

Detecting deception using functional magnetic resonance imaging.

BACKGROUND: The ability to accurately detect deception is presently very limited. Detecting deception might be more accurately achieved by measuring the brain correlates of lying in an individual. In addition, a method to investigate the neurocircuitry of deception might provide a unique opportunity to test the neurocircuitry of persons in whom deception is a prominent component (i.e., conduct disorder, antisocial personality disorder, etc.). METHODS: In this study, we used functional magnetic resonance imaging (fMRI) to show that specific regions were reproducibly activated when subjects deceived. Subjects participated in a mock crime stealing either a ring or a watch. While undergoing an fMRI, the subjects denied taking either object, thus telling the truth with some responses, and lying with others. A Model-Building Group (MBG, n = 30) was used to develop the analysis methods, and the methods were subsequently applied to an independent Model-Testing Group (MTG, n = 31). RESULTS: We were able to correctly differentiate truthful from deceptive responses, correctly identifying the object stolen, for 93% of the subjects in the MBG and 90% of the subjects in the MTG. CONCLUSIONS: This is the first study to use fMRI to detect deception at the individual level. Further work is required to determine how well this technology will work in different settings and populations.

Adolescent↗

PubMed2005

Decreased cortical response to verbal working memory following sleep deprivation.

STUDY OBJECTIVE: To investigate the cerebral hemodynamic response to verbal working memory following sleep deprivation. DESIGN: Subjects were scheduled for 3 functional magnetic resonance imaging scanning visits: an initial screening day (screening state), after a normal night of sleep (rested state), and after 30 hours of sleep deprivation (sleep-deprivation state). Subjects performed the Sternberg working memory task alternated with a control task during an approximate 13-minute functional magnetic resonance imaging scan. SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Results from 33 men (mean age, 28.6 +/- 6.6 years) were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: Subjects performed the same Sternberg working memory task at the 3 states within the magnetic resonance imaging scanner. Neuroimaging data revealed that, in the screening and rested states, the brain regions activated by the Sternberg working memory task were found in the left dorsolateral prefrontal cortex, Broca's area, supplementary motor area, right ventrolateral prefrontal cortex, and the bilateral posterior parietal cortexes. After 30 hours of sleep deprivation, the activations in these brain regions significantly decreased, especially in the bilateral posterior parietal cortices. Task performance also decreased. A repeated-measures analysis of variance revealed that subjects at the screening and rested states had similar activation patterns, with each having significantly more activation than during the sleep-deprivation state. CONCLUSIONS: These results suggest that human sleep-deprivation deficits are not caused solely or even predominantly by prefrontal cortex dysfunction and that the paretal cortex, in particular, and other brain regions involved in verbal working memory exhibit significant sleep-deprivation vulnerability.

Adolescent↗

PubMed2005

Decreased brain activation during a working memory task at rested baseline is associated with vulnerability to sleep deprivation.

STUDY OBJECTIVE: To examine whether differences in patterns of brain activation under baseline conditions relate to the differences in sleep-deprivation vulnerability. DESIGN: Using blood oxygenation level dependent (BOLD) functional magnetic resonance imaging, we scanned 33 healthy young men while they performed the Sternberg working memory task following a normal night of sleep and again following 30 hours of sleep deprivation. From this initial group, based on their Sternberg working memory task performance, we found 10 subjects resilient to sleep deprivation (sleep deprivation-resilient group) and then selected 10 age- and education-matched subjects vulnerable to sleep deprivation (sleep deprivation-vulnerable group). SETTING: Inpatient General Clinical Research Center and outpatient functional magnetic resonance imaging center. PATIENTS OR PARTICIPANTS: Data from 10 young men (mean age 27.8 +/- 1.7 years) in the sleep deprivation-resilient group and 10 young men (mean age 28.2 +/- 1.9 years) in the sleep deprivation-vulnerable group were included in the final analyses. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We compared functional magnetic resonance imaging BOLD signal at rested baseline and sleep deprivation states in the 2 groups. As hypothesized, following sleep deprivation, both groups showed significant decreases in global brain activation compared to their rested group baseline. At rested baseline and in the sleep-deprivation state, the sleep deprivation-resilient group had significantly more brain activation than did the sleep deprivation-vulnerable group. There were also differences in functional circuits within and between groups in response to sleep deprivation. CONCLUSIONS: These preliminary data suggest that patterns of brain activation during the Sternberg working memory task at the rested baseline and the sleep-deprivation state, differ across individuals as a function of their sleep-deprivation vulnerability.

Adolescent↗

PubMed2004

Acute vagus nerve stimulation using different pulse widths produces varying brain effects.

BACKGROUND: Vagus nerve stimulation (VNS) is an approved treatment for epilepsy and has been investigated in clinical trials of depression. Little is known about the relationship of VNS parameters to brain function. Using the interleaved VNS /functional magnetic resonance imaging (fMRI) technique, we tested whether variations of VNS pulse width (PW) would produce different immediate brain activation in a manner consistent with single neuron PW studies. METHODS: Twelve adult patients with major depression, treated with VNS, underwent three consecutive VNS/fMRI scans, each randomly using one of three PWs (130 micros, 250 micros, or 500 micros). The data were analyzed with SPM2. RESULTS: Global activations induced by PWs 250 and 500 were both significantly greater than that induced by PW 130 but not significantly different from each other. For global deactivation, PWs 130 and 250 were both significantly greater than PW 500 but not significantly different from each other. Regional similarities and differences were also seen with the various PWs. CONCLUSIONS: The data confirm our hypothesis that VNS at PW 500 globally produces no more activation than does PW 250, and PW 130 is insufficient for activation of some regions. These data suggest that PW is an important variable in producing VNS brain effects.

Adult↗

PubMed2004

An efficient SNP system for mouse genome scanning and elucidating strain relationships.

A set of 1638 informative SNP markers easily assayed by the Amplifluor genotyping system were tested in 102 mouse strains, including the majority of the common and wild-derived inbred strains available from The Jackson Laboratory. Selected from publicly available databases, the markers are on average approximately 1.5 Mb apart and, whenever possible, represent the rare allele in at least two strains. Amplifluor assays were developed for each marker and performed on two independent DNA samples from each strain. The mean number of polymorphisms between strains was 608+/-136 SD. Several tests indicate that the markers provide an effective system for performing genome scans and quantitative trait loci analyses in all but the most closely related strains. Additionally, the markers revealed several subtle differences between closely related mouse strains, including the groups of several 129, BALB, C3H, C57, and DBA strains, and a group of wild-derived inbred strains representing several Mus musculus subspecies. Applying a neighbor-joining method to the data, we constructed a mouse strain family tree, which in most cases confirmed existing genealogies.

Alleles↗

PubMed2003

Retroposon compensatory mechanism hypothesis not supported: Zfa knockout mice are fertile.

It is hypothesized that autosomal retroposons compensate for the loss of their inactivated essential X-chromosome progenitors during spermatogenesis. Here we test this Retroposon Compensatory Mechanism (RCM) hypothesis using the Zfy gene family. The mouse autosomal retroposon Zfa is expressed in testes at the same developmental time points at which Zfx levels decline, which correspond to the time of male sex chromosome inactivation, suggesting that Zfa may compensate for the loss of Zfx during spermatogenesis. We examined the effect of Zfa-targeted mutagenesis on spermatogenesis in three genetically distinct mouse strains. Surprisingly, Zfa knockout mice showed no detectable fertility, sperm count, or testes morphology defects. We therefore conclude that Zfa is not an essential gene for spermatogenesis and fertility. This surprising finding now challenges the RCM hypothesis at least for the Zfy gene family. It also forces us to reevaluate the original data underpinning the RCM hypothesis for this family and to propose alternative hypotheses.

Aging↗

PubMed2003

Environmental exposure to polychlorinated biphenyls among raccoons (Procyon lotor) at the paducah gaseous diffusion plant, Western Kentucky, USA.

An investigation involving raccoons (Procyon lotor) as a sentinel species at the Paducah Gaseous Diffusion Plant (PGDP) in Western Kentucky (USA) delineated the extent of exposure to polychlorinated biphenyls (PCBs) and PCB spatial distribution. Raccoon exposure to PCBs was demonstrated through analysis of subcutaneous fat, abdominal fat, liver, and brain tissues from raccoons collected at the PGDP but also was clearly evident in raccoons from a reference area situated along the Ohio River (USA). Raccoons with the highest tissue PCB concentrations appeared to be those inhabiting areas nearest the plant itself and most likely those that ventured into the plants interior. Male raccoons at the PGDP had similar concentrations of total PCBs in subcutaneous fat (1.86 +/- 0.64 microg/g) as males from the reference site (1.41 +/- 0.35 microg/g), but females had higher PCB body burdens than those at the reference site (9.90 +/- 6.13 microg/g vs 0.75 +/- 0.40 microg/g). Gross measurements of exposure to radiation-producing materials revealed that counts per minute exceeded background in 61% of PGDP raccoons compared with 27% at the reference site and five raccoons at the PGDP had beta counts that were more than twice the background. Differences among trapping success, growth rates, and serum chemistry parameters were noted but may have been related to habitat and other environmental and population density factors.

Animal Feed↗

PubMed2003

Environmental polychlorinated biphenyl exposure and cytochromes P450 in raccoons (Procyon lotor).

An investigation involving raccoons as a sentinel species at the Paducah Gaseous Diffusion Plant (PGDP) and Ballard Wildlife Management Area in western Kentucky (USA) delineated the extent of exposure to polychlorinated biphenyls (PCBs). Three separate measures of hepatic cytochrome P450 (CYP) induction were used to evaluate raccoon physiological responses to PCB exposure. Hepatic CYP induction was estimated via determination of total CYP, dealkylase activities, and immunoreactive proteins. There were no differences in raccoon biomarker responses between study sites. Significant relationships between and among PCB residues and biomarkers indicated that hepatic CYP induction had occurred in response to PCB exposure. Pentoxyresorufin O-deethylase (PROD) activity, CYP1A1, and CYP1A2 were biomarkers most closely associated with PCB exposure. The rank order of responses was CYP1A1 > CYP1A2 > PROD > ethoxyresorufin O-deethylase (EROD) as related to raccoon liver PCB concentrations, whereas the order was CYP1A1 > PROD > EROD > CYP1A2 when regressed with total PCB concentrations in abdominal fat.

Animals↗

PubMed2002

Cln3(Deltaex7/8) knock-in mice with the common JNCL mutation exhibit progressive neurologic disease that begins before birth.

Juvenile-onset neuronal ceroid lipofuscinosis (JNCL; Batten disease) features hallmark membrane deposits and loss of central nervous system (CNS) neurons. Most cases of the disease are due to recessive inheritance of an approximately 1 kb deletion in the CLN3 gene, encoding battenin. To investigate the common JNCL mutation, we have introduced an identical genomic DNA deletion into the murine CLN3 homologue (Cln3) to create Cln3( Deltaex7/8) knock-in mice. The Cln3( Deltaex7/8) allele produced alternatively spliced mRNAs, including a variant predicting non-truncated protein, as well as mutant battenin that was detected in the cytoplasm of cells in the periphery and CNS. Moreover, Cln3( Deltaex7/8) homozygotes exhibited accrual of JNCL-like membrane deposits from before birth, in proportion to battenin levels, which were high in liver and select neuronal populations. However, liver enzymes and CNS development were normal. Instead, Cln3( Deltaex7/8) mice displayed recessively inherited degenerative changes in retina, cerebral cortex and cerebellum, as well as neurological deficits and premature death. Thus, the harmful impact of the common JNCL mutation on the CNS was not well correlated with membrane deposition per se, suggesting instead a specific battenin activity that is essential for the survival of CNS neurons.

Alternative Splicing↗

PubMed2002

Novel Sxr(a) ES cell line offers hope for Y chromosome gene-targeted mice.

A mouse targeted for a Y Chromosome gene has not been reported. Because the Y Chromosome is present in only one copy, and most of its genes are critical for germ cell development, such a mouse would likely be infertile. Thus, we describe a new reproductive strategy to enable transmission of targeted Y Chromosome genes to subsequent generations. The strategy uses two segregating copies of Y Chromosome genes to mimic the autosomal condition. To achieve this, we developed a new embryonic stem cell line from the XYSxr(a) mouse, which carries a duplication of the gene-rich Y Chromosome short arm. Importantly, we demonstrate germ line transmission of the YSxr(a) chromosome and describe this significant new tool as a practical solution to enable reproduction in mice targeted for Y Chromosome genes.

Animals↗