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Biomedical subjects

R J Seitz

Publications and source records attributed to R J Seitz.

At least 109 records · Page 6Linked to original sources

Cerebral hemodynamics during sensorimotor activation in humans.

We studied the time course and magnitude of cerebral blood flow velocity (CBFV) changes in the middle cerebral artery (MCA) and the regional cerebral blood flow (rCBF) in the MCA territory during stimulation of the left sensorimotor cortex. Healthy right-handed male subjects were examined during performance of right-hand finger movement sequences, vibratory stimulation, and somatosensory discrimination. In somatosensory discrimination there were significant increases of the mean CBFV (4.8 +/- 9.9 cm/s; P < 0.01) and the mean rCBF (10.2 +/- 4.2 ml.100 g-1.min-1; P < 0.01), whereas no significant changes of the mean CBFV and rCBF occurred in finger movement sequences or vibratory stimulation. During all stimulation sessions the mean CBFV changes increased rapidly and reached a first maximum 3.3 +/- 0.3 s after stimulation onset. Simultaneous measurements of relative mean CBFV changes in both MCAs revealed left-right differences during voluntary finger movement sequences (left MCA, 14.3 +/- 10.6%; right MCA, 0.9 +/- 11.6%; P < 0.001) corresponding to a higher mean rCBF change in the left MCA territory. In the two tasks involving finger movements there was an increase of the respiratory rates (4.3 +/- 3.8 breaths/min; P < 0.05) and the pulse rates (11.6 +/- 5.5 beats/min; P < 0.05), respectively. Our data demonstrate a correspondence of mean CBFV and rCBF changes evoked by sensorimotor activation in the human brain. Furthermore, cerebral hemodynamic changes related to motor activity are accompanied by cardiorespiratory effects.

Adolescent↗

Balo's concentric sclerosis followed by MRI and positron emission tomography.

We report a case of Balo's concentric sclerosis diagnosed in vivo by characteristic MRI changes and stereotactic biopsy. Follow-up after 6 months of immunosuppressive treatment demonstrated virtually complete clinical remission, reduction of the white matter lesions on MRI and normalisation of regional cerebral glucose metabolism as assessed by positron emission tomography not only in white matter but also in the cerebral grey matter structures with input from the affected regions.

Adult↗

Individual somatotopy of primary sensorimotor cortex revealed by intermodal matching of MEG, PET, and MRI.

A method for comparing estimated magnetoencephalographic (MEG) dipole localizations with regional cerebral blood flow (rCBF) activation areas is presented. This approach utilizes individual intermodal matching of MEG data, of rCBF measurements with [15O]-butanol and positron emission tomography (PET), and of anatomical information obtained from magnetic resonance (MR) images. The MEG data and the rCBF measurements were recorded in a healthy subject during right-sided simple voluntary movements of the foot, thumb, index finger, and mouth. High resolution 3D-FLASH MR images of the brain consisting of 128 contiguous sagittal slices of 1.17-mm thickness were used. MEG/MR integration was performed by superimposing the 3D head coordinate system constructed during the MEG measurement onto the MR image data using identical anatomical landmarks as references. PET/MR integration was achieved by a phantom-validated iterative front-to-back-projection algorithm resulting in one integrated MEG/PET/MR image. The estimated dipole locations followed the somatotopic organisation of the task-specific rCBF increases as evident from PET, although they did not match point-to-point. Our results demonstrate that intermodal matching of MEG, PET and MR data provides a tool for relating estimated neuromagnetic field locations to task-specific rCBF changes in individual subjects. Our method offers the perspective of refined dipole modelling.

Adult↗

Individual integration of positron emission tomography and high-resolution magnetic resonance imaging.

We have developed, validated, and employed a technique of retrospective spatial alignment and integrated display of positron emission tomographic (PET) and high-resolution magnetic resonance (MR) brain images. The method was designed to improve the anatomical evaluation of functional images obtained from single subjects. In the first computational step, alignment of PET and MR data sets is achieved by iteratively matching in three orthogonal views the outermost scalp contours derived from front-to-back projections of each data set. This procedure avoids true three-dimensional modeling, runs without user interaction, and tolerates missing parts of the head circumference in the image volume, as usually the case with PET. Thereafter, high-resolution MR sections corresponding to the PET slices are reconstructed from the spatially transformed MR data. In a phantom study of this method, PET/MR alignment of the phantom's surface was accurate with average residual misfits of 2.17 to 2.32 mm as determined in three orthogonal planes. In-plane alignment of the phantom's insertion holes was accurate with an average residual misfit of 2.30 mm. In vivo application in six subjects allowed the individual anatomical localization of regional CBF (rCBF) responses obtained during unilateral manual exploration. In each subject, the maxima of the rCBF activations in the hand area were precisely allocated to gray matter in the anterior or posterior wall of the central sulcus. The configuration of the rCBF responses closely followed the gyral structures. The technique provided a better topographical understanding of rCBF changes in subtraction images of PET activation studies. It opens the perspective for studies of structural-functional relationships in individual subjects.

Brain↗

Vibratory stimulation increases and decreases the regional cerebral blood flow and oxidative metabolism: a positron emission tomography (PET) study.

The aim of this study was to examine the hypothesis, if the activation of some cerebral structures due to physiological stimulation is accompanied by deactivations of other structures elsewhere in the brain. A vibratory stimulus was applied to the right hand palm of healthy volunteers and the regional cerebral blood flow (rCBF) and regional cerebral oxygen metabolism (rCMRO2) were measured with positron emission tomography (PET). Regional analysis and voxel-by-voxel plots indicated that the stimulation induced increases and decreases of the rCBF were coupled to increases and decreases of the rCMRO2. The increases were localized in the left primary somatosensory area (SI), the left secondary somatosensory area (SII), the left retroinsular field (RI), the left anterior parietal cortex, the left primary motor area (MI), and the left supplementary motor area (SMA). The decreases occurred bilaterally in the superior parietal cortex, in paralimbic association areas, and the left globus pallidus. The increases and decreases of the rCBF and rCMRO2 were balanced in such a way that the mean global CBF and CMRO2 did not change compared with rest. We conclude that the decreases of the cerebral oxidative metabolism indicated regional depressions of synaptic activity.

Adult↗

Positron emission tomography studies of the somatosensory system in man.

Activity in the human somatosensory system was measured by regional cerebral blood flow (rCBF) and by the binding of [11C]nimodipine to L-type Ca2+ channels. These physiological variables were considered to be indicators of neuronal and synaptic activity. In general, structures in the cerebellum, thalamus and the somatosensory cortices which increased their rCBF in response to somatosensory stimulation also showed high binding of [11C]nimodipine. Voluntary movements carried out largely independently of sensory feedback, natural somatosensory stimulation and passive stimulation of the somatosensory system all activate the somatosensory system. However, it is possible by subtraction techniques to show that differences in activations between these conditions exist in the cerebellum and the somatosensory cortices in the anterior part of the parietal lobe.

Brain Mapping↗

Functional anatomy of language processing: neuroimaging and the problem of individual variability.

This paper discusses the long-standing concepts of a participation of frontal opercular and inferior parietal cortex in high-order language processing with respect to contradictory inferences from recent positron emission tomographic (PET) activation studies (cf. Petersen et al. [49]). The main thrust of the present argument is that the technique of intersubject PET image averaging may be inappropriate due to intersubject variability. Evidence is presented which suggests that intersubject variability is at least two-fold: (i) Intraoperative stimulation has demonstrated diversity in location of language functions in the left frontal and temporoparietal association cortex; (ii) Morphometrical imaging studies have demonstrated diversity of brain shape and gyral pattern which is difficult to correct by anatomical standardization of individual brains. Both factors add noise in spatially standardized PET images and may render circumscribed high-order language foci undetectable. It is argued that PET studies of higher cognitive functions including language must focus on individual anatomo-functional organization using techniques such as intrasubject averaging.

Arousal↗

Accuracy and precision of the computerized brain atlas programme for localization and quantification in positron emission tomography.

The computerized brain atlas programme (CBA) provides a powerful tool for the anatomical analysis of functional images obtained with positron emission tomography (PET). With a repertoire of simple transformations, the data base of the CBA is first adapted to the anatomy of the subject's brain represented as a set of magnetic resonance (MR) or computed tomography (CT) images. After this, it is possible to spatially standardize (reformat) any set of tomographic images related to the subject, PET images, as well as CT and MR images, by applying the inverse atlas transformations. From these reformatted images, statistical images, such as average images and associated error images corresponding to different groups of subjects, may be produced. In all these images, anatomical structures can be localized using the atlas data base and the functional values can be evaluated quantitatively. The purpose of this study was to determine the spatial and quantitative accuracy and precision of the calculated regional mean values. Therefore, the CBA was applied to regional CBF (rCBF) measurements with [11C]fluoromethane and PET on 26 healthy male volunteers during rest and during three different physiological stimulation tasks. First, the spatial accuracy and precision of the reformation process were determined by measuring the spread of defined anatomical structures in the reformatted MR images of the subjects. Second, the mean global CBF and the mean rCBF in the average PET images were compared with the global CBF and rCBF in the original PET images. Our results demonstrate that the reformation process accurately transformed the individual brains of the subjects into the standard brain anatomy of the CBA. The precision of the reformation process had an SD of approximately 1 mm for the lateral dislocation of midline structures and approximately 2-3 mm for the dislocation of the inner and outer brain surfaces. The quantitative rCBF values of the original PET images were accurately represented in the reformatted PET images. Moreover, this study shows that the application of the CBA improves the analysis of functional PET images: (a) The average PET images had a low background noise [0.4 ml/100 g/min +/- 0.7 (SD)] compared to the mean rCBF changes specifically induced by physiological stimulation. (b) The reformatted PET images had a voxel volume of 10.9 mm3. Owing to this high sampling resolution, it was possible to differentiate the mean rCBF changes in adjacent activated fields such as the left motor hand area from the sensory hand area and the left premotor cortex.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗

Functional anatomy of storage, recall, and recognition of a visual pattern in man.

With the purpose of mapping the anatomical structures participating in memory of visual patterns, we measured regional cerebral blood flow (rCBF) as an indicator of synaptic metabolism in eleven volunteers during four conditions: rest, visual learning of colored geometrical patterns, recall with the eyes closed, and recognition of the patterns. Learning changed rCBF in the primary visual cortex, visual association areas, temporal pole, anterior hippocampus, dorsal thalamus, caudate nucleus, putamen, and the anterior cingulate cortex. Recall and recognition changed rCBF in other limbic, thalamic, and striatal sectors. Only the highest order parieto-occipital visual areas were activated during recall. These areas were assumed to be the storage sites. It was inferred that the limbic and striatal circuits participating in learning were replaced by other limbic and thalamic circuits to recall and recognize the learned patterns.

Adult↗

Motor learning in man: a positron emission tomographic study.

We measured regional cerebral blood flow (rCBF) with positron emission tomography to study changes in anatomical structures during the course of learning a complicated finger sequence of voluntary movements. Motor learning was accompanied by rCBF increases in the cerebellum, decreases in all limbic and paralimbic structures, and striatal decreases which changed to striatal increases as the motor skill was learned. Simultaneously, activations of initially contributing non-motor parts of the cerebral cortex vanished. Both cerebellar circuits and striatal circuits appear important for the storage of motor skills in the brain.

Adult↗

Cerebral blood flow and substrate utilization in insulin-treated diabetic subjects.

We compared regional cerebral blood flow (rCBF) and arteriojugular vein differences of glucose, ketones, glycerol, lactate, pyruvate, and O2 in eight subjects with well-controlled insulin-dependent diabetes mellitus (IDDM) and in six healthy volunteers. Duration of diabetes was 19.4 +/- 2.1 yr. Measurements were performed before and after 120 min of insulin infusion and concomitant Biostator-controlled normoglycemia. Net uptake of ketones was seen in IDDM subjects before but not after insulin. Net uptake of glucose did not differ significantly between groups. During normoglycemia the molar ratio of O2 to glucose uptake was lower in IDDM than in nondiabetic subjects (4.68 vs. 5.50; P less than 0.05; Wilcoxon test). Small but significant release of lactate and pyruvate was seen in IDDM but not in nondiabetic subjects. The rCBF was measured by 11CH3F and position emission tomography. Global mean CBF was higher in IDDM subjects (64.9 +/- 5.9 vs. 49.3 +/- 2.7 ml.100 g-1.min-1, means +/- SE in nondiabetic subjects, P less than 0.05). rCBF was enhanced in many cortical and subcortical areas, whereas it was decreased in the head of the caudate nucleus. Neuropsychological testing did not reveal obvious cognitive dysfunction. The results imply that a larger fraction of glucose is nonoxidatively metabolized in the IDDM subjects and furthermore indicate an abnormal rCBF pattern in these subjects.

Acetoacetates↗

Enhanced immunocytochemical staining sensitivity in formalin-fixed and paraffin-embedded material by simultaneous use of PAP and ABC.

The simultaneous use of two immunoperoxidase (IP) methods; e.g. the PAP (Peroxidase-antiperoxidase) and ABC (Avidin-Biotin) to localize a single antigen enhances the sensitivity of polyclonal antibodies (FVIII/RAg and laminin) or monoclonal antibodies (MABs) (against human B-, T-cells and macrophages) in routinely formalin fixed and in paraffin embedded material. The increased sensitivity was not accompanied by loss of specificity. With antibodies against Factor VIII related antigen (FVIII/RAg) and laminin the increased staining intensity of blood vessels were demonstrated in experimental rat transplantation tumors. The similar enhancement of immunocytochemical reactions was observed with biopsies of human brain tumors, where the monoclonal antibodies against white blood cells were used. The staining results were of comparable intensity as in snapfrozen tissue or after special embedding procedure for immunocytochemical purposes acc. to Bolton and Mesnard formol sucrose gum, sucrose paraffin; FSGSP).

Animals↗

The blood-nerve barrier in Wallerian degeneration: a sequential long-term study.

The blood-nerve barrier (BNB) for serum proteins was studied after a crush lesion of the murine sciatic nerve or after transsection with persistent Wallerian degeneration. Using single intraperitoneal injections of biotinylated human albumin, transferrin, IgG, and complement components as tracers, the integrity of the BNB during degeneration and regeneration was determined over time. In Wallerian degeneration induced by crush the BNB became increasingly leaky, with a maximum in the distal stump 8 days after crush (i.e., during early regeneration). When regeneration potentials could first be elicited from the small foot muscles and when thinly myelinated nerve fibers were present, the BNB gradually regained its barrier function and was nearly intact on day 30 after crush. After transsection breakdown of the BNB persisted beyond 30 days. The BNB leakage may foster repair by allowing exchange of trophic factors of large molecular size during nerve regeneration.

Animals↗

Toxic effects of triethyldodecylammoniumbromide (TEA-C12) on myelinated nerve fibers and blood-nerve barrier in the mouse.

The blocking effect of triethyldodecylammoniumbromide (TEA-C12), applied locally to the sciatic nerve, was studied in 28 adult BDF1 mice. Clinical parameters, electrophysiological recordings of muscle action potentials evoked by stimulation at the sciatic notch, and morphological aspects are presented. Our results show that both the minimal blocking concentration and half the minimal blocking concentration induce flaccid paresis of the treated hind-limb. There was a complete, long-lasting nerve conduction block due to Wallerian degeneration of the myelinated nerve fibers. In contrast, pain sensation was abolished only on day 4 after application of the minimal blocking concentration, but was preserved during the rest of the time that nerve conduction block was observed. This correspond to the electron microscopic finding of preservation of unmyelinated nerve fibers. Recovery of nerve conduction was characterized electrophysiologically by occurrence of minute polyphasic regeneration potentials between day 18 and 21, clinically by advanced restitution of muscle force on day 64, and morphologically by nerve regeneration. TEA-C12 also induced a disturbance of the blood-nerve barrier, demonstrated using an intraperitoneally administered biotinylated IgG tracer in the endoneurial space. The morphological features of the acute axonal changes of the myelinated nerve fibers including the degeneration of the axonal mitochondria suggest that the neurotoxic effect of TEA-C12 is possibly mediated by interference with the axonal energy supply. The selective affection of myelinated nerve fibers separates TEA-C12 from other neurotoxins that induce changes of the axonal microorganelles or complete Wallerian degeneration of myelinated and unmyelinated nerve fibers. The selectivity for myelinated nerve fibers and the supposed pathogenetic mechanism exhibit some similarities with the human polyneuropathy caused by acute arsenic acid intoxication.

Action Potentials↗

Expression of vimentin and glial fibrillary acidic protein in ethylnitrosourea-induced rat gliomas and glioma cell lines.

The expression of glial fibrillary acidic protein (GFAP) and vimentin was investigated immunohistochemically in 104 experimental gliomas induced by transplancental application of ethylnitrosourea (ENU) in CDF rats. Immunoreactivity for vimentin was prominent in many astrocytic tumor cells and especially in small glioma cells forming anaplastic medulloblastoma-like foci in many tumors. The majority of tumor cells in oligodendroglial tumors were vimentin negative, except for some of the large polymorphous oligodendrogliomas which contained intermingled vimentin positive glioma cells. GFAP immunoreactivity was detectable only in a low fraction of tumor astrocytes and in a few exceptional cases some oligodendroglial tumor cells stained positive. Immunohistochemistry with antibodies against neurofilaments and cytokeratins revealed no staining in tumor cells of ENU-induced gliomas, while all oligodendrogliomatous tumors stained positive for HNK-1. Immunocytological and immunoblot investigations of the two rat glioma cell clones RG2 and F98, which are both derived from ENU-induced gliomas, showed a prominent expression of vimentin in monolayer cultures and in syngeneic intracerebral transplantation tumors. F98 additionally demonstrated a fraction of GFAP positive cells especially in confluent cultures and in intracerebral tumors. RG2, on the other hand, exhibited virtually no GFAP immunoreactivity in culture but showed individual GFAP positive tumor cells in intracerebral tumors. Our results revealed a more precise picture of the cellular differentiation in ENU-induced rat gliomas and in two widely used glioma cell lines. They underline the heterogeneity of experimental rat gliomas which may comprise cells at different stages of differentiation towards oligodendroglial or astroglial phenotype.

Animals↗

Significance of lymphocytes and blood vessel changes for edema formation in polyradiculoneuritis.

Human sural nerve biopsies of eight cases with acute, subacute and chronic polyradiculoneuritis were studied by means of immunohistochemistry to characterize the inflammatory infiltrates. In addition, the structural changes of the endoneurial blood vessels were examined by electron microscopy, since both factors are likely to contribute to disturbances of the blood-nerve barrier. By use of six monoclonal antibodies, it was shown that the inflammatory infiltrates in cases with more acute polyradiculoneuritis are predominantly recruited by Leu 3a- and Leu 4-positive T lymphocytes. In more chronic polyradiculoneuritis beside of few Leu 3a-positive and Leu 4-positive T lymphocytes also B cells occurred. Leu M3-positive macrophages were detected in all cases with fluoride myelin degeneration. Since immunoreactivity for antigens of the HLA-D-locus (Leu-HLA-DR and Leu 10) were present on the infiltrating mononuclear cells, it can be postulated that they represent active and immunocompetent cells. Ultrastructurally, the amount of pinocytotic vesicles in the endothelial cells of the endoneurial blood vessels was increased. Moreover, a prominent folding of the luminal and abluminal surface of vascular endothelial cells and diminution of the intercellular tight junctions were observed. These findings appear suitable to explain the increased leakage of serum proteins across the blood-nerve barrier in polyradiculoneuritis sharing general features of cell-mediated immunity.

Adolescent↗

Vascularization of syngenic intracerebral RG2 and F98 rat transplantation tumors. A histochemical and morphometric study by use of ricinus communis agglutinin I.

The vascularization of intracerebral transplantation tumors of the two rat glioma clones RG2 and F98 was studied in various stages of progressive tumor growth by use of biotinylated Ricinus communis agglutinin I (B-RCA I) in avidin-biotin-peroxidase complex (ABC)-histochemistry. The tumors were induced by stereotactic implantation of 1000 glioma cells into the right caudate nucleus of 26 adult CDF-rats and examined after 10, 14, 18, and 21 days following controlled intracardial perfusion of the host animals. Our histochemical results on paraffin sections demonstrate that B-RCA I selectively stains vascular endothelial cells of arteries, veins, and capillaries not only in the normal rat brain but also in the transplantation tumors. Subsequently morphometric measurements of the B-RCA I-stained sections were performed to define the tumor vascularization in quantitative terms. There was an increase in the mean tumor vessel diameters during tumor growth in both transplantation tumor types leading to values about two times above those of the normal rat striatum. On the contrary, the mean vessel density and the mean vessel surface per tumor area were markedly reduced in the late stages of both tumor types when compared to the normal striatum. The RG2 and F98 transplantation tumors differed with regard to the intercapillary distance, which was two times higher in the F98 transplantation tumors than in the RG2 tumors on day 21. In conclusion, B-RCA I is a very sensitive histochemical marker for rat vascular endothelia on paraffin sections. Moreover, this method appears to provide the possibility for qualitative and quantitative study of the development of vasculature in intracerebral transplantation systems including tumors.

Animals↗