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Biomedical subjects

H Axer

Publications and source records attributed to H Axer.

At least 19 recordsLinked to original sources

[Procalcitonin as a marker for severe sepsis in an immunosuppressed patient].

A 22 year old female was admitted to the emergency department with high fever up to 41,5 degrees C, tachycardia, and arterial hypotension. Clinically, she presented with bilateral pulmonary coarse crackles. Diagnosis on admission was pneumonia with septic shock. Intriguingly, procalcitonin (PCT) was increased early, reaching up to 435 ng/mL, while C-reactive protein levels were only moderately increased, with several days delay. The sepsis was originated from a multi-resistant pseudomonas aeruginosa pneumonia. Remarkably, the course of PCT levels reflected the severity of septic shock in that it paralleled noradrenaline demand. Ten months previously, the patient had been diagnosed with acute disseminated brainstem encephalitis (ADEM), and had received two cycles of intravenous cyclophosphamide. Our case illustrates that PCT is an early marker for sepsis and it indicates that PCT may also be a valuable marker for the severity of sepsis in immunosuppressed patients.

Adult↗

Initial DWI and ADC imaging may predict outcome in acute disseminated encephalomyelitis: report of two cases of brain stem encephalitis.

Two young patients with acute disseminated encephalomyelitis (ADEM) of the brain stem are described. In spite of similar lesion sites in the brain stem, reaching from the upper medulla to the mesencephalon, the outcomes of the patients were very different: one made a full clinical recovery within three weeks while the other remained in a locked-in state more than a year after the disease episode. Both patients also differed in magnetic resonance imaging (MRI) findings on admission. The patient who remained in a locked-in state had pathological diffusion weighted imaging (DWI) scans and decreased apparent diffusion coefficient maps initially, with severe tissue destruction on follow up computed tomography, while the patient who recovered fully showed initially increased apparent diffusion coefficient values and almost complete resolution of MRI changes on follow up. Thus a comparison of these two cases may indicate differences in the underlying pathology in ADEM (vasogenic v cytotoxic oedema) that may be crucial for estimating tissue damage and clinical outcome.

Adult↗

Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle.

Human GLUT11 (encoded by the solute carrier 2A11 gene, SLC2A11) is a novel sugar transporter which exhibits significant sequence similarity with the members of the GLUT family. The amino acid sequence deduced from its cDNAs predicts 12 putative membrane-spanning helices and all the motifs (sugar-transporter signatures) that have previously been shown to be essential for sugar-transport activity. The closest relative of GLUT11 is the fructose transporter GLUT5 (sharing 41.7% amino acid identity with GLUT11). The human GLUT11 gene (SLC2A11) consists of 12 exons and is located on chromosome 22q11.2. In human tissues, a 7.2 kb transcript of GLUT11 was detected exclusively in heart and skeletal muscle. Transfection of COS-7 cells with GLUT11 cDNA significantly increased the glucose-transport activity reconstituted from membrane extracts as well as the specific binding of the sugar-transporter ligand cytochalasin B. In contrast to that of GLUT4, the glucose-transport activity of GLUT11 was markedly inhibited by fructose. It is concluded that GLUT11 is a novel, muscle-specific transport facilitator that is a member of the extended GLUT family of sugar/polyol-transport facilitators.

Amino Acid Sequence↗

In vivo 3D visualization of normal pyramidal tracts in human subjects using diffusion weighted magnetic resonance imaging and a neuronavigation system.

We describe the potential of anisotropic diffusion weighted imaging to visualize the course of large cerebral fiber tracts. Five healthy volunteers were investigated at a field strength of 1.5 Tesla, employing a spin-echo diffusion weighted sequence with gradient sensitivity in six non-collinear directions to visualize the course of the pyramidal tracts. The pyramidal tracts were segmented and reconstructed for three-dimensional visualization. Reconstruction results together with a fusioned high resolution 3D T1 weighted image data set were available in a customized neuronavigation system. Origination in the primary motor cortex, convergence in the centrum semiovale, the posterior limb of the internal capsule, the cerebral peduncles, the splitting at the level of the pons, and the pyramidal decussation were identified in all subjects. Fiber tract maps might have the prospect of guiding neurosurgical interventions, especially when being linked to a neuronavigation system. Other potential applications include the demonstration of the anatomical substrate of functional connectivity in the human brain.

Adult↗

Quantitative estimation of 3-D fiber course in gross histological sections of the human brain using polarized light.

Series of polarized light images can be used to achieve quantitative estimates of the angles of inclination (z-direction) and direction (in xy-plane) of central nervous fibers in histological sections of the human brain. (1) The corpus callosum of a formalin-fixed human brain was sectioned at different angles of inclination of nerve fibers and at different thicknesses of the samples. The minimum, and maximum intensities, and their differences revealed a linear relationship to the angle of inclination of fibers. It was demonstrated that sections with a thickness of 80--120 microm are best suited for estimating the angle of inclination. (2) Afterwards the optic tracts of eight formalin-fixed human brains were sliced at different angles of fiber inclination at 100 microm. Measurements of intensity in 30 pixels in each section were used to calculate a linear function of calibration. The maximum intensities and the differences between maximum and minimum values measured with two polars only were best suited for estimation of fiber inclination. (3) Gross histological brain slices of formalin-fixed human brains were digitized under azimuths from 0 to 80 degrees using two polars only. These sequences were used to estimate the inclination of fibers (in z-direction). The same slices were digitized under azimuths from 0 to 160 degrees in steps of 20 degrees using a quarter wave plate additionally. These sequences were used to estimate the direction of the fibers in xy-direction. The method can be used to produce maps of fiber orientation in gross histological sections of the human brain similar to the fiber orientation maps derived by diffusion weighted magnetic resonance imaging.

Brain↗

Supra- and infrasylvian conduction aphasia.

Fifteen cases of conduction aphasia which were tested with the Aachen Aphasia Test (AAT), are presented. The CT lesion data were transformed to a standard 3D-reference brain referring to the ACPC line. According to the lesion profiles a group of 6 patients had pure suprasylvian lesions, a group of 4 patients had pure infrasylvian lesions, and a group of 5 patients had lesions in both supra- and infrasylvian regions. Suprasylvian conduction aphasics are superior to infrasylvian conduction aphasics in the token test and in repetition tasks. Infrasylvian conduction aphasics use more stereotypes in spontaneous speech than suprasylvian conduction aphasics. Conduction aphasics with both lesion sites perform less well in tests of naming, writing, and comprehension than the pure types. Thus conduction aphasia is a heterogeneous syndrome anatomically and linguistically.

Adult↗

Collagen fibers in linea alba and rectus sheaths. I. General scheme and morphological aspects.

BACKGROUND: The anatomy of the anterior abdominal wall plays a most significant role in surgery. Thus the three-dimensional architecture of the collagen fibers in linea alba and rectus sheaths was investigated in 12 human cadavers. MATERIAL AND METHODS: The linea alba was divided into 14 different anatomical segments in the craniocaudal direction. Two-hundred-micrometer-thick, eosin-stained sections from these segments were analyzed by confocal laser scanning microscopy. In this way the direction of the collagen fibers was estimated in the midline of the linea alba and in the medial parts of the rectus sheaths. Width and thickness of the linea alba and thickness of the rectus sheaths were measured. RESULTS: In the ventral rectus sheath essentially oblique fibril bundles intermingle with each other, while the dorsal rectus sheath consists chiefly of transverse fibril bundles. In the linea alba three different zones of fiber orientation follow each other from ventral to dorsal: The lamina fibrae obliquae consists of intermingling oblique fibers. The lamina fibrae transversae contains mainly transverse fibril bundles, while an inconstant, small lamina fibrae irregularium is composed of oblique fibers. Different regions can be distinguished in the craniocaudal course of the linea alba: supraumbilical part, umbilical part, transition zone, and infraarcuate part. CONCLUSIONS: A new model of fiber architecture of the linea alba was developed that describes the fiber architecture as a three-dimensional, highly structured meshwork of collagen fibers. In contrast to former models, no separate lines of decussation of the fibers could be found.

Abdominal Muscles↗

Collagen fibers in linea alba and rectus sheaths.

BACKGROUND: After the description of a general scheme of the architecture of collagen fibers in linea alba and rectus sheaths, variability and differences of fiber architectures were analyzed to describe their functional role. MATERIALS AND METHODS: Using confocal laser scanning microscopy the diameter of each layer of fibril bundles was measured in linea alba and rectus sheaths of 12 human cadavers, and each fibril bundle was classified according to its orientation (oblique I and II, transverse). RESULTS: The mean diameter of fibril bundles in the supraumbilical region of the linea alba was smaller than in the infraumbilical region, and in the supraumbilical region the thickness of the linea alba was smaller than in the infraumbilical region. Analyzing sex-dependent differences in the fiber architecture of the linea alba, a larger amount of transverse fibers relative to oblique fibers were found in females in infraumbilical regions. The thickness of the infraumbilical linea alba was smaller in females than in males, while its width was larger. CONCLUSIONS: There exist gender differences in the architecture of the linea alba. However, whether these morphological differences demonstrate the adaptability of this fiber architecture to biomechanical stress in raised intraabdominal pressure in pregnancy remains to be proven. The transverse fibers act as a counterpart to the intraabdominal pressure whereas the oblique fibers are involved mainly in movements of the trunk.

Abdominal Muscles↗

Nitric-oxide-induced cGMP synthesis in cholinergic neurons in the rat brain.

Nitric oxide (NO)-mediated cGMP synthesis is localized throughout the rat brain in close proximity to the NO-synthase-containing structures. However, characterization of the cGMP synthesizing structures in terms of co-localization with the classical neurotransmitter systems has not yet been reported. Here we present evidence, using double immunostaining for cGMP and the vesicular acetylcholine transporter, that virtually all of the cholinergic fibers in the cerebral cortex and the majority of the cholinergic fibers in the basal ganglia accumulate cGMP in response to a NO donor. In these areas, only few cGMP-containing fibers were observed not to be part of the cholinergic system. Co-localization between cGMP and the vesicular acetylcholine transporter was only observed to a minor degree in the ventral forebrain, the hippocampus, the reticular thalamic nucleus, and the nucleus ambiguus. No association of cGMP synthesis with the cholinergic system was observed to a similar extent in other brain areas. These results, in combination with literature data on the distribution of cholinergic receptors in the rat brain, suggest that NO has an anterograde and/or retrograde signaling function on subsets of cholinergic neurons.

Acetylcholine↗

Localization of cGMP-dependent protein kinase type II in rat brain.

In brain, signaling pathways initiated by atrial natriuretic peptide, or transmitters which stimulate nitric oxide synthesis, increase cGMP as their second messenger. One important class of target molecules for cGMP is cGMP-dependent protein kinases, and in the present study, biochemical and immunocytochemical analyses demonstrate the widespread distribution of type II cGMP-dependent protein kinase in rat brain, from the cerebral cortex to the brainstem and cerebellum. Also, colocalization of cGMP-dependent protein kinase type II with its activator, cGMP, was found in several brain regions examined after in vitro stimulation of brain slices with sodium nitroprusside. In western blots, cGMP-dependent protein kinase type II was observed in all brain regions examined, although cerebellar cortex and pituitary contained comparatively less of the kinase. Immunocytochemistry revealed cGMP-dependent protein kinase type II in certain neurons, and occasionally in putative oligodendrocytes and astrocytes, however, its most striking and predominant localization was in neuropil. Electron microscopy examination of neuropil in the medial habenula showed localization of the kinase in both axon terminals and dendrites. As a membrane-associated protein, cGMP-dependent protein kinase type II often appeared to be transported to cell processes to a greater extent than being retained in the cell body. Thus, immunocytochemical labeling of cGMP-dependent protein kinase type II often did not coincide with the localization of kinase mRNA previously observed by others using in situ hybridization. We conclude that in contrast to cGMP-dependent protein kinase type I, which has a very restricted localization to cerebellar Purkinje cells and a few other sites, cGMP-dependent protein kinase type II is a very ubiquitous brain protein kinase and thus a more likely candidate for relaying myriad cGMP effects in brain requiring protein phosphorylation.

Animals↗

Whole brain spheroid cultures as a model to study the development of nitric oxide synthase-guanylate cyclase signal transduction.

Whole brain spheroids provide a suitable model to study neurodevelopment. In the literature a role for the nitric oxide (NO)-cyclic guanosine 3',5'-monophosphate (cGMP) signalling pathway during development has frequently been suggested. In this study we investigated whether functional cGMP pathways were present in differentiated spheroids. In 3-week-old spheroids soluble guanylate cyclase was stimulated with N-methyl D-aspartic acid or sodium nitroprusside (NO donor). The results showed that the NO synthase-cGMP pathway is present in the culture system. Soluble guanylate cyclase-dependent cGMP formation was found in NO synthase containing neurons, in neurons of the GABAergic, glutamatergic and cholinergic system, and in astroglia and oligodendroglia. Activation of particulate guanylate cyclase by atrial natriuretic peptide also triggered an increase in cGMP production. Particulate guanylate cyclase was found in astroglia and in microglia as well as in glutamic acid decarboxylase and calbindin containing structures and neuronal NO synthase containing neurons. Chronic inhibition of NO synthase during culture development had no effect on soluble or particulate guanylate cyclase functioning. Similarly, inhibition of soluble guanylate cyclase during culture development did not have any effect on NO synthase and particulate guanylate cyclase functioning. It is concluded that NO synthase and both soluble and particulate guanylate cyclase are present in whole brain spheroid cultures and that their activity can be influenced by several stimuli. The spheroid culture system constitutes a suitable model to study the NO-cGMP pathway during brain development in mammals.

1-Methyl-3-isobutylxanthine↗

Visualization of nerve fiber orientation in gross histological sections of the human brain.

Diffusion weighted magnetic resonance imaging (DWMRI) allows visualization of the orientation of the nervous fibers in the living brain. For comparison, a method was developed to examine the orientation of fibers in histological sections of the human brain. Serial sections through the entire human brain were analyzed regarding fiber orientation using polarized light. Direction of fibers in the cutting plane was obtained by measuring the azimuth with the lowest intensity value at each point, and inclination of fibers in the section was evaluated using fuzzy logic approximations. Direction and inclination of fibers revealing their three-dimensional orientation were visualized by colored arrows mapped into the images. Using this procedure, various fiber tracts were identified (pyramidal tract, radiatio optica, radiatio acustica, arcuate fascicle, and 11 more). Intermingled fibers could be separated from each other. The orientation of the fiber tracts derived from polarized light microscopy was validated by confocal laser scanning microscopy in a defined volume of the internal capsule, where the fiber orientation was studied in four human brains. The polarization method visualizes the high degree of intermingled fiber bundles in the brain, so that distinct fiber pathways cannot be understood as solid, compact tracts: Neighbouring bundles of fibers can belong to different systems of fibers distinguishable by their orientation.

Aged↗

Localization and age-related changes of nitric oxide- and ANP-mediated cyclic-GMP synthesis in rat cervical spinal cord: an immunocytochemical study.

An immunocytochemical technique was used to study the localization and developmental aspects of cyclic GMP (cGMP)-synthesizing structures in the cervical spinal cord of 2-week and 3-month-old Lewis rats in response to the nitric oxide (NO) donor sodium nitroprusside (SNP) and/or atrial natriuretic peptide (ANP). By using cell-specific markers, the cell structures involved were investigated. To visualize cGMP, a combined technique of low- and high-power magnification, using a confocal laser scanning microscope was used. NOS-mediated cGMP synthesis was observed in the cervical spinal cord in laminae I, II and III in 14-day-old rats, which activity was mainly absent at the age of 3 months. The involvement of NO in the NMDA-mediated increase in cGMP immunostaining (cGMP-IS) was demonstrated by the absence of cGMP-IS in slices incubated in the presence of NMDA together with the NOS inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME). This NO-mediated effect of NMDA on cGMP-IS was completely absent in the 3-month-old rats. ANP-mediated cGMP synthesis resulted in an increase in cGMP in laminae I and II, which was generally similar at both ages. Astrocytes in both white and gray matter were found to be cGMP-IS in the basal, NO- and ANP-stimulated conditions. Using confocal laser microscopy, NO-mediated cGMP synthesis was observed in large cholinergic terminals nearby motor neurons in the ventral horn. An extensive colocalization between NO-stimulated cGMP synthesis and parvalbumin-positive (GABAergic) neurons and fibers was observed in all laminae. In the ANP-stimulated condition, a colocalization with parvalbumin structures was found in laminae II and III. No NO- or ANP-mediated cGMP synthesis was found in fibers immunopositive for the presynaptic glutamate transporter, serotonin, or tyrosine hydroxylase.

Age Factors↗

Mapping of fiber orientation in human internal capsule by means of polarized light and confocal scanning laser microscopy.

The nervous fibers in the human internal capsule were mapped according to their three-dimensional orientation. Four human cadaver brains were cut into comparable and standardized sections parallel to the ACPC-plane, stained with DiI, and analyzed using a combination of confocal and polarized light microscopy at the same time. This combination provides information about the structure and orientation of the fibers in great detail with confocal microscopy, and information about the localization and orientation of long myelinated fiber tracts with polarization microscopy. The internal capsule was parcellated in the areas CI 1 to CI 4 containing fibers of distinct orientation and structure, which enriches the macroscopically definable parcellation in the anterior and posterior limb. Fibers of the anterior thalamic peduncle intermingle with frontopontine tract fibers. Single fibers connect the caudate and the lentiform nucleus. The pyramidal tract is located in the anterior half of the posterior limb intermingled with fibers of the superior thalamic peduncle. Parietooccipitopontine fibers are located in the posterior part of the posterior limb. The slopes of the different systems of fibers change continuously in the anterior posterior direction of the internal capsule. Using the 3D orientation of fibers as a criterion for parcellation, as well as the description of bundles as a collection of fibers belonging to particular tracts leads to a more function-related description of the anatomy of the internal capsule. The method can be used for interindividual, sex- or age-related comparisons of particular systems of fibers.

Cadaver↗

An aphasia database on the internet: a model for computer-assisted analysis in aphasiology.

A web-based software model was developed as an example for data mining in aphasiology. It is used for educating medical and engineering students. It is based upon a database of 254 aphasic patients which contains the diagnosis of the aphasia type, profiles of an aphasia test battery (Aachen Aphasia Test), and some further clinical information. In addition, the cerebral lesion profiles of 147 of these cases were standardized by transferring the coordinates of the lesions to a 3D reference brain based upon the ACPC coordinate system. Two artificial neural networks were used to perform a classification of the aphasia type. First, a coarse classification was achieved by using an assessment of spontaneous speech of the patient which produced correct results in 87% of the test cases. Data analysis tools were used to select four features of the 30 available test features to yield a more accurate diagnosis. This classifier produced correct results in 92% of the test cases. The neural network approach is similar to grouping performed in group studies, while the nearest-neighbor method shows a design more similar to case studies. It finds the neurolinguistic and the lesion data of patients whose AAT profiles are most similar to the user's input. This way lesion profiles can be compared to each other interindividually. The Aphasia Diagnoser is available on the Web address http://fuzzy.iau.dtu.dk/aphasia.nsf and thus should facilitate a discussion about the reliability and possibilities of data-mining techniques in aphasiology.

Aphasia↗

NO-mediated cGMP synthesis in cholinergic neurons in the rat forebrain: effects of lesioning dopaminergic or serotonergic pathways on nNOS and cGMP synthesis.

Nitric oxide synthase (NOS) activity and NO-mediated cGMP synthesis were studied in the rat forebrain of control animals and animals which had received a unilateral lesioning of dopaminergic or serotonergic pathways. Lesioning of the dopaminergic innervation using 6-hydroxydopamine resulted in a 50% decrease in NOS activity in the lesioned frontal cortex and caudate putamen. Lesioning of the serotonergic innervation using 5,7-dihydroxytryptamine had no effect on NOS activity. NO-mediated cGMP accumulation in rat forebrain slices was not affected by 6-hydroxydopamine or 5,7, -dihydroxytryptamine lesioning. Using cGMP immunocytochemistry, it was demonstrated that NO-mediated cGMP synthesis was absent from dopaminergic, serotonergic, GABA-ergic and neuronal NOS-containing nerve fibres. A minor colocalization of cGMP immunoreactivity was found in parvalbumin-containing fibres in the cortex. Extensive colocalization between cGMP immunoreactivity and the acetylcholine transporter was found in all cortical areas and in the caudate putamen. There was no effect of the lesions on this colocalization. These results demonstrate NO-mediated cGMP accumulation in cholinergic fibres in the forebrain of the rat and suggest an anterograde signalling function of NO in cholinergic neuronal systems in the cortex and caudate putamen of the rat.

1-Methyl-3-isobutylxanthine↗

Morphological asymmetry in anterior limb of human internal capsule revealed by confocal laser and polarized light microscopy.

The fiber structure in the anterior limb of the internal capsule was investigated in a region where stereotactic lesions (anterior capsulotomy) result in successful treatment of obsessive-compulsive disorder (OCD). Eight human hemispheres were sectioned in comparable planes parallel to the ACPC plane. Microscopic slices were labeled with DiI and analyzed with confocal laser and polarized light microscopy. Three distinct systems of fibers were detected. Single fibers run from the caudate nucleus to the lentiform nucleus. The anterior thalamic peduncle connects the mediodorsal and partially the anterior thalamic nucleus with the frontal lobe. The frontopontine tract system connects the frontal lobe with the pons. This fiber tract occupies 38% of the anterior limb and is arranged in small bands. Right-left comparison of morphometric parameters of these bundles demonstrated that more and smaller bundles were located on the left-hand side than on the right-hand side. Tendencies for this configuration were noticeable in all brains investigated, with statistical significance in one brain. These morphological differences correlate with functional differences, as it was possible to demonstrate right hemispheric dysfunctions in cases of OCD. The benefit of anterior capsulotomy in OCD is generally seen in the interruption of fronto-basal ganglia-thalamic loops by disconnecting the anterior thalamic peduncle. In addition, the frontopontine fiber tract is disconnected in this stereotactic procedure.

Aged↗