An x-ray atlas of the sagittal plane of the chicken diencephalon and its use in the precise localization of brain sites.
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A female patient showed rejection of a T-lymphocyte-depleted bone-marrow graft from her phenotypically HLA-identical father. Before bone-marrow transplantation, there was strong recipient anti-donor cellular cytotoxic reactivity directed against several minor histocompatibility (mH) antigens, including the male-specific H-Y antigen. After conditioning treatment, no recipient anti-donor cytotoxic activity could be detected, and good graft function was shown a month after transplantation. Thereafter, however, graft function deteriorated rapidly, while recipient-derived anti-donor cellular cytotoxic reactivity, against similar mH antigens, reappeared. The recipient-derived cytotoxic T lymphocytes could completely inhibit growth of donor haemopoietic progenitor cells both before and after bone-marrow transplantation. Thus, cytotoxic T lymphocytes can survive very intensive conditioning regimens, and residual recipient cytotoxic T lymphocytes directed against mH antigens expressed on donor haemopoietic progenitor cells may cause graft rejection after HLA-identical T-lymphocyte-depleted bone-marrow transplantation.
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Videomicroscopy was used to image 'intrinsic' responses over the rat barrel cortex through a closed cranial window during controlled whisker stimulation. With a Macintosh IIfx running Image 1.49 VDM, video frames from a CCD camera were captured and averaged before, during and after whisker stimulation. The technique presented here is a functional imaging modality--using conventional videomicroscopic equipment, a small computer, and public domain NIH Image software--with a temporal resolution of 33 ms. Images can be obtained directly from the CCD camera or recorded to videotape for post hoc analysis. Pixel by pixel comparison of prestimulation images to images obtained during stimulation revealed changes in the reflectance characteristics of cortex and vessels overlying the barrel field. Imaged responses superimposed on barrel histology to map intrinsic signal matched barrels of the stimulated whiskers in every case. Video imaging of the rat barrel cortex provides a useful method for rapid targeting for other experimental protocols and has potential for analyzing localized responses to physiologic stimuli in vivo.
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Specific domains of the NS4 and NS5 gene products of hepatitis C virus have been identified using hydrophilicity profiles for the prediction of potential immunogenic regions, and epitope scanning techniques. Peptides synthesised on the basis of such data show excellent reactivity in the ELISA format. Introduction of a glycine-glycine spacer between two peptides (NS4-12 and NS5-44) to give a single chimeric peptides does not appear to impair immunoreactivity. An ELISA based on the chimeric peptide and a Core-NS3 recombinant protein correctly diagnoses a cohort of haemodialysed patients, three commercial HCV panels and the sera of a negative control population.
Neurotoxicity can be divided into three levels: depletion, degeneration and denervation. The first level is determined by the transmitter content, and the second and third levels, which require anatomical evaluation, can be analyzed by quantitative immunocytochemistry on a specific neurotransmitter system. An antibody specific to serotonin (5-HT) can reveal detailed normal as well as degenerative morphology of 5-HT neurons. Quantitative alterations of 5-HT fibers in a particular brain region indicate degenerative or plastic changes. This study demonstrates quantitative immunocytochemistry by using image analysis of immunostained 5-HT fibers in selectively-bred, alcohol-preferring and nonpreferring rats, which are known to have divergent drinking behaviors, and 5-HT contents in specific brain regions. The method of the image analysis is described in detail and the advantages and disadvantages of using this method to detect the degeneration of a particular fiber system are discussed. The 'area density' traditionally measured in image analysis was converted (with Zhou-Tam formula) into 'volume density' to correct the mismeasurement of fibers through the optical depth. Quantitative immunostaining shows that the difference in 5-HT fiber density in particular brain regions between the two rat lines is consistent with changes in content of the 5-HT/5-HIAA and hypersensitivity of 5-HT1 a receptor. This result indicates either (a) the 5-HT content is too low to be detected in the nerve terminals; (b) degeneration of 5-HT fibers occurs in P rats sometime during development; or (c) a smaller number of 5-HT fibers was preprogrammed in the brain regions of P than NP rats.(ABSTRACT TRUNCATED AT 250 WORDS)
The association between personality and resting brain activity was investigated. Personality was assessed using the NEO-Five-factor Inventory (NEO-FFI) and resting brain activity was indexed by eyes closed EEG spectral magnitude from four frequency bands over the entire cortex. Results suggest that there are differences between males and females in the NEO-FFI personality traits. The NEO FFI traits were associated with lower frequency brain activity in both males and females. Mild significant and consistent associations were found between delta and theta activity across all cortical regions with Extraversion and Conscientiousness. There were few associations between personality traits and alpha and beta activity, this was shown in males only. Fewer associations between personality and faster frequency bands such as alpha may be due to the methodological problem of using fixed alpha bands. Multiple regression analyses showed that individual alpha frequencies had a greater contribution to personality traits than fixed band alpha waves.
Sudden cardiac death due to ventricular arrhythmias is a major cause of mortality in patients with heart failure (HF). As HF develops, a host of changes occur at multiple levels, spanning the spectrum from subcellular/molecular to organ-system levels. These changes, collectively referred to as "cardiac remodeling," predispose to electrical disturbances via multiple mechanisms. In humans, most arrhythmias are reentrant by nature, involving circulatory wavefront(s) that excite the heart in rapid, irregular succession. Hence, by definition, reentrant excitation occurs at the multicellular intact tissue level, and therefore, a complete understanding of its dynamics and underlying mechanisms requires investigation of electrophysiological properties (such as action potentials and calcium transients) in intact tissue preparations where cells are electrically coupled to one another. While molecular and cellular studies are critical for identifying changes in individual myocytes, only recently have we begun to understand how these complex changes can create an environment ripe for arrhythmias. In particular, the integrative technique of optical action potential mapping was used in recent years to address key questions regarding changes in network electrical properties of the failing myocardium. In the present manuscript, we review recent findings from mapping studies in the experimental laboratory as they relate to the characterization of the arrhythmic substrate of the failing heart, followed by a discussion of clinical mapping approaches used to identify key characteristics of atrial and ventricular arrhythmias in patients with HF.
Multifractal analysis has been applied to evaluate biological tissues, which are composed of complex structures. We carried out multifractal analyses in a group of healthy young and elderly subjects to examine age-related white matter microstructural changes on T2-weighted MR images without any visible abnormal intensity, and to correlate such changes with age-related cognitive decline. Comparison between the two age groups showed that Deltaalpha (established as the most suitable index of heterogeneity in our previous report) in the frontal region was significantly higher in the elderly group, but no significant group difference was found in Deltaalpha in the parieto-occipital region. The Trail-Making Test score (a measure of executive dysfunction) was significantly higher in the elderly group. In the elderly group, the Trail-Making Test score was positively correlated with Deltaalpha in the frontal region, but not in the parieto-occipital region. These results suggest that microstructural changes in the white matter preferentially occur in the frontal region with normal aging, and these changes are associated with executive cognitive decline reflective of frontal-subcortical dysfunction.
Assessment of the spatial dispersion of ventricular refractory periods has become an important part of electrophysiological study in both experimental and clinical settings, because inhomogeneity of ventricular refractoriness is associated with an increased risk of life-threatening ventricular arrhythmias. Previous animal studies in dog and sheep have demonstrated that local ventricular fibrillation (VF) intervals measured from the heart surface correlate well with the ventricular effective refractory periods measured from the same ventricular sites. We hypothesise that local VF intervals may also predict the ventricular refractory periods in human hearts, hence, can be used to assess the spatial dispersion of refractoriness and to predict the risk of ventricular arrhythmias.
An automated method for placement of 3D rat brain atlas-derived volumes of interest (VOIs) onto PET studies has been designed and evaluated. VOIs representing major structures of the rat brain were defined on a set of digitized cryosectioned images of the rat brain. For VOI placement, each PET study was registered with a synthetic PET target constructed from the VOI template. Registration was accomplished with an automated algorithm that maximized the mutual information content of the image volumes. The accuracy and precision of this method for VOI placement was determined using datasets from PET studies of the striatal dopamine and hippocampal serotonin systems. Each evaluated PET study could be registered to at least one synthetic PET target without obvious failure. Registration was critically dependent upon the initial position of the PET study relative to the synthetic PET target, but not dependent on the amount of synthetic PET target smoothing. An evaluation algorithm showed that resultant radioactivity concentration measurements of selected brain structures had errors=2% due to misalignment with the corresponding VOI. Further, radioligand binding values calculated from these measurements were found to be more precise than those calculated from measurements obtained with manually drawn regions of interest (ROIs). Overall, evaluation results demonstrated that this atlas-derived VOI method can be used to obtain unbiased measurements of radioactivity concentration from PET studies. Its automated features, and applicability to different radioligands and brain regions, will facilitate quantitative rat brain PET assessment procedures.
Modern imaging techniques that visualize disease-specific organ neurotransmitter or protein receptor sites are increasingly able to define pathological processes on a molecular level. One of those imaging modalities, positron emission tomography (PET), for the assessment of brain neuroreceptor binding has revolutionized the in vivo assessment of biologic markers that may be related to human behavior. Such studies may help identify chemical targets that may be directly related to psychiatric pathology and, thus, opportunities for pharmacological intervention. In this review, we describe results from PET studies in eating disorders (EDs). Eating disorders are frequently debilitating illnesses that are quite homogeneous in their presentation. Those studies that identified particular serotonin and dopamine receptor alterations can distinguish recovered ED subjects from controls as well as ED subgroups. Furthermore, correlations of receptor binding with behavioral constructs, such as harm avoidance or novelty seeking, could be found. These recognized receptors may now help us to move away from rather nonspecific treatment approaches in psychiatric research and clinic to the possibility of more syndrome- and symptom-specific treatment approaches.
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We used magnetoencephalography (MEG) to assess the degree of hemispheric activation in eleven normal, right-handed subjects with no history of neurological disorder or learning disability during performance of a word- and a face-recognition tasks. Neuromagnetic activity was recorded using a whole-head system, and the sources of the recorded magnetic fields were modeled as single equivalent current dipoles. Early (<200 msec) cerebral activation, defined by the number of dipoles identified by the data-fitting algorithm, was localized in the occipital cortex during both tasks, as expected. During the language task, the extent of the later (>200 msec) cerebral activation was approximately double in the left hemisphere in almost all subjects, involving temporal and temporoparietal areas. In contrast, during the face-recognition task, the corresponding activation was mostly symmetrical across the two occipital lobes, also involving the posterior-inferior aspect of the right temporal lobe. Our results suggest that the MEG is a suitable method of assessing noninvasively hemispheric specialization for language.
With the expansion of comparative genome analysis across different mammals, there is an increasing need to have well-defined banded karyotypes for the species chosen for investigation. In this context, the steadily growing gene mapping data in the donkey urgently require a framework whereby alignment/comparison of genetic information can be readily made with equids and other mammalian species. Hence a GTG-banded karyotype of the donkey (Equus asinus; EAS) is presented, along with schematic drawings and nomenclature of the banded chromosomes. In addition, the most characteristic features of individual chromosomes are described and their relative size estimated. Using the FISH approach, the location of nucleolous organizer regions (NORs) and telomeric repeat sequences (TTAGGG) were detected. Where possible, information on asine chromosomes is supplemented with known/likely equine and human homologues. The study thus primarily aims to provide an appropriate cytogenetic basis for the donkey chromosomes, so that research focused on gene mapping and comparative genomics in this species can be reported under a common format.
Positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) with intravenously administered 15O-labeled water and an adaptation of the Kety autoradiographic model are well suited to the study of functional-anatomical correlations within the human brain. This model requires arterial blood sampling to determine rCBF from the regional tissue radiotracer concentration (Cr) recorded by the tomograph. Based upon the well-defined, nearly linear relation between Cr and rCBF inherent in the model, we have developed a method for estimating changes in rCBF from changes in Cr without calculating true rCBF and thus without arterial sampling. This study demonstrates that quantitative functional brain mapping does not require the determination of rCBF from Cr when regional neuronal activation is expressed as the change in rCBF from an initial, resting-state measurement. Patterned-flash visual stimulation was used to produce a wide range of increases in rCBF within the striate cortex. Changes in occipital rCBF were found to be accurately estimated directly from Cr over a series of 56 measurements on eight subjects. This adaptation of the PET/autoradiographic method serves to simplify its application and to make it more acceptable to the subject.