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Biomedical subjects

D Stiller

Publications and source records attributed to D Stiller.

At least 19 recordsLinked to original sources

Brain tissue biomechanics in cortical contusion injury: a finite element analysis.

The controlled cortical impact model has been used extensively to study focal traumatic brain injury. Although the impact variables can be well defined, little is known about the biomechanical trauma as delivered to different brain regions. This knowledge however could be valuable for interpretation of experiment (immunohistochemistry etc.), especially regarding the comparison of the regional biomechanical severity level to the regional magnitude of the trauma sequel under investigation. We used finite element (FE) analysis, based on high resolution T2-weighted MRI images of rat brain, to simulate displacement, mean stress, and shear stress of brain during impact. Young's Modulus E, to describe tissue elasticity, was assigned to each FE in three scenarios: in a constant fashion (E = 50 kPa), or according to the MRI intensity in a linear (E = [10, 100] kPa) and inverse-linear fashion (E = [100, 10] kPa). Simulated tissue displacement did not vary between the 3 scenarios, however mean stress and shear stress were largely different. The linear scenario showed the most likely distribution of stresses. In summary, FE analysis seems to be a suitable tool for biomechanical simulation, however, to be closest to reality tissue elasticity needs to be determined with a more specific approach, e.g. by means of MRI elastography.

Animals↗

DNA polymorphisms in the tyrosine hydroxylase and GNB3 genes: association with unexpected death from acute myocardial infarction and increased heart weight.

Sudden and unexpected death from myocardial infarction (MI) is one of the most commonly observed findings in forensic medicine. To investigate the biochemical and genetic background of this disease we investigated the genotypes for two polymorphisms associated with hypertension: TH01, a tetrameric microsatellite in the tyrosine hydroxylase gene and the single nucleotide polymorphism C825T in the GNB3 gene in 116 sudden deaths from MI (78 males, 38 females) and in a control group of 137 deaths from natural causes other than MI (52 males, 85 females). For TH01 no correlation with the prevalence of MI was found. For C825T, results were different. While for the male individuals allelic frequencies and genotype distributions were similar in both groups, T-homozygosity was significantly more common in female fatalities from MI than in the female control group (24% versus 7%; Relative Risk 2.29). Nevertheless, neither for TH01 nor for C825T an association with heart weight was found. Thus our results demonstrate that the C825T polymorphism may play a role in the development of myocardial infarctions, at least in females. They also demonstrate that the genetic component in complex diseases like MI may depend on the gender of the patients. As the influence of this polymorphism on arterial blood pressure appears to be relatively small, and G-proteins are involved in numerous intracellular signal cascades it can be speculated that T-homozygosity at this locus might influence the incidence or mortality of cardiovascular disease via hitherto unknown mechanisms.

Adult↗

Sudden cardiac death in hereditary hemochromatosis: an underestimated cause of death?

Hereditary hemochromatosis (HH) is a frequent autosomal recessive disease which causes iron-overload of various organs. Of all northern European affected individuals, 90-95% show 1 of 3 known point mutations in the HFE gene. Symptoms and organs involved can vary considerably: Only a small fraction of the 200,000-400,000 persons affected in Germany develop the classical picture of liver cirrhosis and/or pancreatic fibrosis. Nevertheless, the life expectancy of persons with moderate or even subclinical symptoms is reduced, in many cases due to myocardial damage leading to cardiomyopathy with greatly increased risk of sudden cardiac death. Although the high prevalence of HH suggests that sudden cardiac death due to cardiac HH is a relatively common cause of death, the forensic literature lacks such reports. We present the case of sudden cardiac death in a young man with histological findings of massive cardial hemochromatosis which is characterized by the fact that none of the three known mutations for HH were found. This case demonstrates that genetic screening alone might not be sufficient to identify all persons at risk to developing HH.

Adult↗

Long-time in-vivo metabolic monitoring following experimental brain contusion using proton magnetic resonance spectroscopy.

In a Sham-controlled study we applied proton magnetic resonance spectroscopy (1H-MRS) at 4.7 T to a model of experimental traumatic brain contusion. The time course of cerebral metabolite changes was monitored in serial investigation in 14 Sprague Dawley rats up to 4 weeks after trauma. 6 animals served as controls. 1H-MRS spectra were acquired from a voxel covering the hippocampus/basal ganglia ipsi and contralateral to the lesion. Metabolites ratios of the injured hemisphere were compared to those ipsilateral in Sham animals and to those of the contralateral side in the trauma animals. NAA/Cr ratio and Glu/Cr ratio, possible markers of neuronal loss, persistently decreased after trauma to a minimum of -40% and -20% versus controls, respectively. One week after trauma Cho/Cr ratio was strongly increased by 73%. This might indicate a high inflammatory activity at that time. Lac/Cr ratio showed long-lasting and continuing increases up to 2000% versus controls as a sign of permanently shifted posttraumatic energy metabolism. 1H-MRS proved to be a useful non-invasive method for in-vivo monitoring of posttraumatic metabolism also in models of brain contusion. In single cases however, accompanying haemorrhage can potentially prevent useful data acquisition.

Animals↗

Determination of contusion and oedema volume by MRI corresponds to changes of brain water content following controlled cortical impact injury.

The time-course of brain contusion/oedema development as visualised by high-resolution MRI was compared to brain water content following experimental brain contusion. 36 Sprague-Dawley rats underwent Controlled Cortical Impact Injury (CCII), 24 served as controls. In 16 animals serial T2 weighted MRI investigations at 1 h, 4 h, 24 h and 7 d after CCII were performed, in 44 rats hemispheric brain water content was determined at the same time points by wet dry weight method. MRI lesion volume (mm3) and brain water content of injured hemisphere (%) showed for absolute and relative values a strictly parallel course. Significant posttraumatic increases had a maximum at 24 hours. Values on day 7 were below those of 1st h in both methods. The simple non-invasive MRI method quantifies contusion and surrounding penumbra according to elevated tissue water signal. The invasive wet dry weight method quantifies changes of hemispheric brain water content that are likely to take place in contusion core and surrounding penumbra. Therefore, from a theoretical aspect both methods seem comparable. Following experimental brain contusion, the simple MRI method might be an equally sufficient way to describe post-traumatic or post-therapeutic changes of lesion size and brain oedema.

Animals↗

Assessment of shooting distance on the basis of bloodstain analysis and histological examinations.

A 28-year-old man was shot using a pump-gun. The main question to be resolved was whether the biological stain pattern on the suspect's trousers, and in particular the bloodstains, can provide evidence to assess the shooting distance between the suspect and the position of the victim's body. The biological stain pattern (i.e. bloodstains and brain tissue) showed backspatters from the shot entrance wound on the back of the head, while the victim was lying face down and the suspect was standing close behind his head.

Adult↗

New insights into the hemodynamic blood oxygenation level-dependent response through combination of functional magnetic resonance imaging and optical recording in gerbil barrel cortex.

Fast, low-angle shoot functional magnetic resonance imaging (fMRI), based on the blood oxygenation level-dependent (BOLD) effect, was combined with optical recording of intrinsic signals (ORIS) and 2-deoxyglucose labeling in gerbil barrel cortex. We observed over the activated barrel a positive BOLD signal and increased levels of deoxyhemoglobin and total hemoglobin during each period of prolonged (30 sec) D2 vibrissal stimulation. These data show that the hemodynamic basis of this fMRI signal is not necessarily a washout of deoxyhemoglobin, as generally assumed. Instead, they suggest that a positive BOLD signal can also be caused by a local increase of blood volume, even if deoxyhemoglobin levels are persistently elevated. We also show that this alternative interpretation is consistent with theoretical models of the BOLD signal. The changes in BOLD signal and blood volume, which are most tightly correlated with the periodic stimulation, peak at the site of neuronal activation. These results contribute to the understanding of the hemodynamic mechanisms underlying the BOLD signal and also suggest analysis methods, which improve the spatial localization of neuronal activation with both fMRI and ORIS.

Animals↗

1H-MR spectroscopic monitoring of posttraumatic metabolism following controlled cortical impact injury: pilot study.

Proton magnetic resonance spectroscopy (1H-MRS) has been increasingly utilised in experimental traumatic brain injury for characterisation of posttraumatic metabolic dysfunction. Following human brain injury pathological findings correlated with outcome measures. Combined with conventional T2-weighted MR imaging MRS is a sensitive tool to evaluate metabolic changes in brain tissue following trauma. Studies have been restricted so far to diffuse axonal injury models and fluid percussion injury. Using a high resolution scanner at 4.7 T, MRI combined with 1H-MRS was applied in a pilot study to the controlled cortical impact injury model of experimental brain contusion (CCII). Eight Sprague-Dawley rats were investigated, of which two served as controls. Four animals were injured 24 h after craniotomy, two investigated at 72 h post craniotomy. MRS/MRI indicated a transient brain oedema development and metabolic changes induced by the craniotomy itself. Following CCII MRI demonstrated that the area of contusion as well as the surrounding brain oedema increased twofold in size within 24 h (p < 0.05). MRS showed an immediate increase of N-acetylaspartate (NAA) and glutamate ipsilateral to the contusion and a drop of NAA on the contralateral side. MRS/MRI investigations in the CCII model demonstrated a potential to further elucidate the pathophysiology following traumatic brain contusion.

Animals↗

Strain diversity in major surface protein 2 expression during tick transmission of Anaplasma marginale.

Specific major surface protein 2 (MSP2) variants are expressed by Anaplasma marginale within the tick salivary gland and, following transmission, are expressed during acute rickettsemia. In previous work, we have shown that a restricted pattern of MSP2 variants is expressed in the salivary glands of Dermacentor andersoni ticks infected with the South Idaho strain of A. marginale. Now we demonstrate that the identical restriction does not apply to two other strains of A. marginale, and that different variants are also expressed when the same strain is transmitted by different Dermacentor spp. This indicates that antigenic diversity among strains is maintained in tick transmission and may be a significant constraint to MSP2 vaccine development.

Amino Acid Sequence↗

Restriction of major surface protein 2 (MSP2) variants during tick transmission of the ehrlichia Anaplasma marginale.

Anaplasma marginale is an ehrlichial pathogen of cattle that establishes lifelong persistent infection. Persistence is characterized by rickettsemic cycles in which new A. marginale variant types, defined by the sequence of the expressed msp2 transcripts, emerge. The polymorphic msp2 transcripts encode structurally distinct MSP2 proteins and result in an antigenically diverse and continually changing A. marginale population within the blood. In this manuscript, we used sequence analysis of msp2 transcripts to show that a restricted repertoire of variant types, designated SGV1 and SGV2, is expressed within the tick salivary gland. The same SGV1 and SGV2 variant types were expressed in ticks regardless of the variant types expressed in the blood of infected cattle at the time of acquisition feeding by the ticks. Importantly, subsequent tick transmission to susceptible cattle resulted in acute rickettsemia composed of organisms expressing only the same SGV1 and SGV2 variant types. This indicates that the msp2 expressed by organisms within the tick salivary gland predicts the variant type responsible for acute rickettsemia and disease. This restriction of transmitted A. marginale variant types, in contrast to the marked diversity within persistently infected cattle, supports development of MSP2 vaccines to prevent acute rickettsemia in tick-transmitted infections.

Amino Acid Sequence↗

Dermacentor hunteri (Acari: Ixodidae): an experimental vector of Anaplasma marginale and A. ovis (Rickettsiales: Anaplasmataceae) to calves and sheep.

The experimental vector competence of laboratory-reared Dermacentor hunteri Bishopp for Anaplasma marginale Theiler and Anaplasma ovis Lestoquard was evaluated by delayed transfer of male ticks from infected to susceptible Holstein calves and from infected to susceptible domestic sheep, respectively. After feeding for 4 or 5 d on rickettsemic acquisition hosts, the ticks were held off the host at 26 degrees C, approximately 93% RH, and a photoperiod of 14:10 (L:D) h for 7 or 8 d, then test fed for 5 or 7 d. Additionally, ticks test-fed for 5 d on 2 susceptible calves were removed, held off the host for 7 d, and test-fed for 5 d on a 3rd susceptible calf to test the tick's ability to transmit A. marginale by delayed serial transfer. Tick transmission of A. marginale to 3 test calves and A. ovis to 3 test sheep was demonstrated by blood smear and indirect immunofluorescence serology. These data indicate that males of D. hunteri, a tick commonly found on desert bighorn, Ovis canadensis Shaw, in the southwestern United States and northern Mexico, may be competent natural vectors of these organisms present in desert bighorn populations.

Anaplasma↗

Functional magnetic resonance imaging of a human auditory cortex area involved in foreground-background decomposition.

Auditory foreground-background decomposition is a pattern recognition process which combines simultaneous and sequential grouping in complex sound sequences. Using functional magnetic resonance imaging with reduced scanner noise and stimulation through a new type of earphones, we investigated the possibility that this process activates topographically distinct areas of human auditory cortex. A basic matching-to-sample task with variable tones (sequential grouping) caused significant activity in three separate landmark-related territories on the supratemporal plane. A similar task in the presence of a strongly masking acoustic background pattern to challenge simultaneous grouping led to the distinction of the subterritory in which foreground signal-related or task-related signal properties were exclusively seen. In contrast to the remainder of territories the level of activity and the periodicity of the signal time-course was resistant to the masking influence of the background. This suggests that auditory foreground-background decomposition involves a specialized non-primary auditory cortex field. Generally, the findings demonstrate functional parcellation of auditory cortex for which the evidence in humans, in contrast to other primates, is only indirect to date.

Acoustic Stimulation↗

Electrodynamic headphones and woofers for application in magnetic resonance imaging scanners.

Electrodynamic speakers compatible with (functional) magnetic resonance imaging (MRI) are described. The speakers magnets are removed, their function is replaced by the scanner's magnetic field, resulting in an uncommon but efficient operation. The method can be used with headphones as well as woofers. Functional MRI is not associated with any known biological risks, but as a method for visualization of task-specific activation of brain regions it is undesirably noisy. Thus, it requires both noise protection and efficient sound transmission systems for delivering acoustic stimuli to subjects. Woofers could possibly be used in active noise-control systems. The speakers described in this paper can be used for either task.

Acoustics↗

Statistical methods in functional magnetic resonance imaging with respect to nonstationary time-series: auditory cortex activity.

In awake animal and human auditory cortices, it is a common experience with electrophysiological and suitable imaging methods for responses to steady stimulation to be strongly state-dependent and to exhibit nonstationarities, even over short periods of observation. If such nonstationary behavior is also reflected by hemodynamic responses in the human auditory cortex, conventional methods of analysis of fMRI data, although applicable for instance to largely stationary responses in visual and other cortices, may be misleading in attempts to parcellate auditory cortex into fields and to demonstrate functional maps. Time-Windows, described in this article as a convenient tool for the detection and analysis of time-variant brain activities, solves some of these problems. Time-Windows demonstrates that activity is evoked reliably in three separate territories of human auditory cortex, parts of which may show nonstationary behavior, depending on the auditory stimuli and tasks.

Adult↗

Lateralized processing of speech prosodies in the temporal cortex: a 3-T functional magnetic resonance imaging study.

Prosodic modulation of speech provides information about emotional states of speakers (affective prosodies) or serves as syntactic markers to change linguistic aspects of speech (linguistic prosodies). Previous electrophysiological investigations and studies on patients with right or left hemisphere damage showed nonuniform results with respect to lateralization of prosodic processing. In this study 20 healthy right-handed volunteers were investigated with functional magnetic resonance imaging of the acoustically responsive areas on the supratemporal plane while detecting phonemes as control targets or prosodies in strings of nonsense syllables and adjectives, the latter randomly intonated in a declarative, interrogative, commanding, happy, or sad fashion. In control task A the phoneme /a/ was detected in the syllables. In control task B the phoneme /a/ was detected in the adjectives, and in the experimental task C the sad intonations (affective) and in the experimental task D the interrogative intonations (linguistic) had to be detected in the same material. In task A intensity-weighted volumes of activated voxels were not different in the two hemispheres (laterality index 0). In task B with an irrelevant phoneme detection with respect to prosodic material, the population split into two subgroups with similar right or left hemispheric lateralization of activity leading to an absolute laterality index of 26.8 across all subjects. During detection of affective prosodies (task C), lateralization was maintained yet the absolute laterality index reduced to 14.5, while there was no lateralization during detection of linguistic prosodies. The sum of activations in the two hemispheres was the same across all tasks and subgroups, which suggests that the lateralizations occurring with presentation and detection of prosodic material depend on a redistribution of activity between hemispheres.

Adolescent↗

The distribution of Dermacentor hunteri and Anaplasma sp. in desert bighorn sheep (Ovis canadensis).

The ixodid tick Dermacentor hunteri has been collected intermittently this century, primarily from desert bighorn sheep (Ovis canadensis). Anaplasma spp. are intraerythrocytic rickettsial parasites of ungulates and are vectored in the western United States by ticks of the genus Dermacentor. We tested the hypotheses that D. hunteri would be found infesting all populations of desert bighorn, and that all infested populations would be seropositive for Anaplasma sp. Dermacentor hunteri was found on desert bighorn throughout their range in the Mojave and Sonoran deserts of the southwestern United States and northern Mexico, but not in any portion of the Chihuahuan desert of New Mexico and eastern Arizona or in Baja California Sur, Mexico. Using an indirect immunofluorescence antibody test (IIF), 8 populations of desert bighorn in California with D. hunteri were seropositive for Anaplasma sp. (n = 160). Four populations of desert bighorn with D. hunteri in Arizona (n = 69), 1 in Nevada (n = 22), and I in Utah (n = 14) with D. hunteri were seronegative. Six populations of desert bighorn were uninfested with D. hunteri and were also seronegative. Of these populations, 1 was in California (n = 19), 2 were in New Mexico (n = 33), 2 were in Utah (n = 30), and 1 was in Baja California Sur (n = 14). We found no support for either of our original hypotheses and concluded that both D. hunteri and Anaplasma sp. are limited in their distribution among desert bighorn. We also suggest a cautionary approach to translocations of desert bighorn given the high prevalence of ticks and the unknown effects of Anaplasma sp. on free-ranging bighorn.

Anaplasma↗

Antibody against an Anaplasma marginale MSP5 epitope common to tick and erythrocyte stages identifies persistently infected cattle.

A protein epitope of major surface protein 5 (MSP5), defined by monoclonal antibody (MAb) ANAF16C1, is conserved among Anaplasma species (E. S. Visser, T. C. McGuire, G. H. Palmer, W. C. Davis, V. Shkap, E. Pipano, and D. P. Knowles, Jr., Infect. Immun. 60:5139-5144, 1992) and is expressed in the salivary glands of infected ticks. A competitive inhibition ELISA (cELISA) for the detection of bovine anti-MSP5 antibodies was developed by using purified recombinant MSP5 fusion protein and MAb ANAF16C1. The specificity of the recombinant-MSP5 cELISA within North America was established by using 261 serum samples from cattle in the regions of Hawaii and Northern Ontario where anaplasmosis is not endemic and from cattle proven by splenectomy or subinoculation of whole blood into susceptible splenectomized recipients to be uninfected. The maximum percent inhibition by these sera was 18%. Sera known to be positive were obtained from 35 cattle either experimentally inoculated with infected erythrocytes or exposed to infected Dermacentor andersoni ticks. Thirty-four of the 35 serum samples inhibited MAb ANAF16C1 binding by > or = 25%. During acute infection, the MSP5 cELISA detected antibodies prior to or concomitantly with the appearance of rickettsiae in erythrocytes. Antibodies were detectable in sera from persistently infected cattle inoculated as long as 6 years previously.

Anaplasma↗