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Biomedical subjects

A Weindl

Publications and source records attributed to A Weindl.

At least 37 records · Page 2Linked to original sources

Cellular localization of endothelin receptor mRNAs (ETA and ETB) in brain tumors and normal human brain.

We performed in situ hybridization (ISH), using radioactively labeled deoxyoligonucleotides, to localize endothelin (ET) receptor subtype mRNAs (ETA and ETB) in a series of meningiomas in comparison to normal human meninges. Our examination also addressed the cerebellum adjacent to the meninges investigated. Tumor cells of all meningiomas examined showed strong hybridization signals for ETA receptor mRNA, whereas for ETB receptor mRNA only weak hybridization signals could be detected in endothelial cells of tumor blood vessels and in some cell clusters. mRNAs for neither ET receptor were detectable in normal leptomeninges. In human cerebellum we found ETA receptor mRNA only in large blood vessels; ETB receptor mRNA was intensely expressed in Bergmann glial cells. Neither subtype was detectable in neurons.

Base Sequence↗

Dysfunctional activation of subcortical nuclei in palatal myoclonus detected by high-resolution MRI.

Magnetic resonance images that were sensitized to changes in cerebral blood oxygenation state demonstrated dysfunctional activation of the dentate nuclei, the left inferior olivary nucleus and the left red nucleus in a 56-year-old patient with palatal myoclonus. These findings represent the first demonstration of movement-related activation of cerebellar, brainstem and midbrain nuclei in a single subject and at a spatial resolution comparable to that of anatomic MR images.

Brain Stem↗

Striatal dopamine D2 receptors in patients with narcolepsy measured with PET and 11C-raclopride.

We investigated in vivo D2 receptor binding using 11C-raclopride and PET in the striatum of 17 subjects with the narcoleptic syndrome. Putamen and caudate nucleus 11C-raclopride uptake was comparable in the total patient group and controls, and the tracer uptake was similar in the HLA-DR2-positive (n = 12) and HLA-DR2-negative (n = 5) narcoleptic subjects. There was a significant increase in 11C-raclopride uptake in the putamen of narcoleptic subjects older than 31 years (n = 11) when compared with age-matched controls (n = 15). There was no evidence of involvement of the striatal D2 dopaminergic neurotransmitter system in the basic pathophysiology of the narcoleptic syndrome despite an age-related increase in putaminal 11C-raclopride uptake.

Adolescent↗

Patch-clamp study of membrane properties and GABA-activated currents of rat magnocellular supraoptic neurons in thin slice preparation.

The magnocellular neurons of the rat supraoptic nucleus were investigated by using (a) the patch-clamp technique on thin brain slice preparations to demonstrate voltage- and GABA-activated ionic currents, and (b) immunohistochemistry to demonstrate the expression of the beta 2 and beta 3 subunits of the GABAA-receptor on their membrane surface and the contents of the neuropeptides vasopressin and oxytocin. During electrophysiological recording in the whole-cell mode neurons were stained with Lucifer Yellow and camera lucida drawings were made. Two types of neurons could be distinguished by their different K(+)-currents, an inactivating and a noninactivating type. All neurons had a fast Na+ inward current. GABAA-activated currents were characterized by investigation of their ionic conductance and by blocking experiments with the GABAA-antagonist bicuculline.

Animals↗

Increased striatal glucose consumption in Sydenham's chorea.

Positron emission tomography and 18F-fluorodeoxyglucose were used to measure the regional cerebral glucose consumption in a 15-year-old choreatic girl with classical Sydenham's chorea shortly after the onset of hyperkinetic movements and 5 months later after chorea had resolved and in a 74-year-old hemichoreatic woman with long-standing hyperkinesia as a residuum of Sydenham's chorea in adolescence. Whereas cerebellar, thalamic, and cortical glucose consumption was within normal limits in both patients, lentiform and caudate glucose consumption was significantly increased in both hemispheres of the 15-year-old patient and in the hemisphere contralateral to the chorea in the 74-year-old patient. In the younger patient, striatal glucose consumption returned to normal after her hyperkinesia had disappeared with antibiotic therapy. The observation of an increase in striatal glucose consumption in Sydenham's chorea, in contrast to the decrease of this variable encountered in the vast majority of other choreatic disorders, leads to questioning the pathophysiology of chorea in humans and suggests the use of emission tomographic measurement of variables related to cerebral energy metabolism for differential diagnosis in choreatic disorders.

Adolescent↗

Determination of nerve growth factor concentrations in human samples by two-site immunoenzymometric assay and bioassay.

Nerve growth factor is a neurotrophic protein which is known to act on sympathetic and sensory neurons and on the magnocellular cholinergic neurons of the basal forebrain. We quantified nerve growth factor in human tissue and body fluids by two methods, a rapid and sensitive two-site immunoenzymometric assay and a bioassay using dissociated chick dorsal root ganglion neurons. The two-site immunoenzymometric assay detects nerve growth factor in concentrations as low as 0.5-2.5 ng/l. Using a monoclonal antibody to mouse nerve growth factor, we found that the signal of the antibody for recombinant human nerve growth factor is about 60-90% of the signal for mouse nerve growth factor. As a control for the specificity of our data, a bioassay for nerve growth factor was performed and the results showed a good correlation. The highest nerve growth factor concentrations were found in sciatic nerve (2.5 ng/g wet weight), cardiac atrium muscle (1.5 ng/g wet weight) and in the central nervous system in the hippocampus (1.9 ng/g wet weight). Lower nerve growth factor concentrations were measured in human sera (0.2 ng/g wet weight). No nerve growth factor was detectable in cerebrospinal fluid. The distribution of human nerve growth factor-rich tissues is similar to that reported for rat tissues.

Animals↗

Motor responses evoked by magnetic brain stimulation in Huntington's disease.

In 34 patients with manifest Huntington's disease (HD), and in 21 first-degree offspring without clinical signs or symptoms, the sizes, central motor latencies (CMLs) and variation in latencies of EMG responses (MEPs) following transcranial magnetic brain stimulation were studied in muscles of the upper and lower extremities. In subgroups of patients and their offspring median and tibial nerve somatosensory evoked potentials (SEPs) and electrically elicited long-loop reflexes (LLRs) in hand muscles were also investigated. Increased MEP thresholds were observed in 10% of the HD offspring, while CML, latency variability and MEP amplitudes always lay within normal range. In contrast, SEPs were abnormal in 33%. In HD patients MEPs were found to be abnormal in up to 72% of patients when all available response parameters were taken into consideration. MEP abnormalities correlated with the duration of motor symptoms and the severity of choreic motor activity. When both MEPs and SEPs were evaluated, abnormalities could be detected in 91% of all HD patients. We suggest that abnormal MEPs might reflect an altered excitability of the cortico-spinal system as a consequence of basal ganglia dysfunction, rather than a structural damage of the investigated descending pathways. To localize the pathological mechanism responsible for altered LLRs, a "loop analysis" was performed by recording LLRs, MEPs and SEPs in the same patients. Alterations of LLRs correlated best with abnormal SEPs and might therefore be explained by reduced somatosensory input to the motor cortex.

Adolescent↗

Distribution of neuropeptide Y in the prosencephalon of man and cotton-head tamarin (Saguinus oedipus): colocalization with somatostatin in neurons of striatum and amygdala.

The presence, chromatographic properties and localization of neuropeptide Y was demonstrated in postmortem human brain areas of neurologically and neuropsychiatrically normative controls using immunocytochemistry and high performance liquid chromatography combined with radioimmunoassay. NPY-immunoreactivity was found in many regions of the prosencephalon. Numerous perikarya and fibers were present in the neocortex, basal ganglia and limbic-hypothalamic areas. A moderate number of neurons and fibers was observed in the basal forebrain, including the septal complex. A comparative immunohistochemical investigation in perfusion-fixed brains of the old-world ape Saguinus oedipus revealed an almost identical distribution of NPY-immunoreactivity with only minor differences. Colocalization experiments on 1-2 microns thin consecutive paraffin sections revealed a large number of NPY neurons throughout the human neostriatum and amygdaloid complex that were also positive for somatostatin. Our findings indicate that detection of neuropeptides in fresh or fixed post-mortem human tissue by different immunochemical methods may actually reflect the in vivo conditions. In addition, the wide distribution of NPY throughout the human brain and its colocalization with other neurotransmitters suggests a physiological role as neuroactive substance, i.e. neuromodulator in the primate central nervous system.

Amygdala↗

Demonstration of atrial natriuretic peptide/cardiodilatin (ANP/CDD)-immunoreactivity in the salt gland of the Pekin duck.

A novel peptide hormone, atrial natriuretic factor/cardiodilatin (ANP/CDD), was recently isolated and characterized from mammalian heart. Its presence has been demonstrated in several organs that contribute to water and sodium homeostasis, such as salivary glands. This study demonstrates the presence of ANP/CDD immunoreactivity in the salt gland of Pekin ducks by high performance liquid chromatography, radioimmunoassay and immunocytochemistry, using a specific antibody against atriopeptide I. A small number of distinct, ovoid or cuboid shaped ANP/CDD-immunoreactive cells were localized in the connective tissue surrounding and separating the central secretory tubules, whereas no immunostaining was observed in the peripheral tubules. Salt glands of ducks that were adapted to salt water revealed a significant hypertrophy of their secretory lobules. However, no differences were found between the number or localization of immunoreactive cells in the salt gland of salt water-acclimatized ducks and nonstimulated glands of ducks that were housed with ad libitum access to fresh water. Our results indicate that ANP/CDD may play a role in the regulation of sodium secretion in the salt gland of aquatic birds.

Animals↗

Neuropeptide Y-like immunoreactive neurons in the human olfactory bulb.

Neuropeptide Y-like (NPY) immunoreactivity was localized in the adult human olfactory bulb by the unlabeled antibody enzyme (peroxidase anti-peroxidase; PAP) technique in vibratome sections. The majority of NPY-immunoreactive somata was localized in the white matter surrounding the anterior olfactory nucleus. Immunoreactive neurons were less numerous within the anterior olfactory nucleus and within the olfactory bulb layers. NPY-immunoreactive fibres were present in the white matter, the anterior olfactory nucleus, and in the olfactory bulb layers. Fibres within the white matter were generally aligned in a straight path parallel to the long axis of the olfactory bulb and tract. Fibres within the anterior olfactory nucleus showed no clear orientation and displayed numerous branching points. Coiled plexus of NPY-immunoreactive fibres were present in the glomerular layer of the olfactory bulb. Additional characteristics of the NPY-immunoreactive neurons were studied after decolouring the chromogen and restaining the sections with aldehydefuchsin to demonstrate the presence of lipofuscin granules and also with gallocyanin chrome alum to stain the Nissl substance. This analysis showed that the neurons belong to the class of non-pigmented nerve cells.

Aged↗

CSF somatostatin is elevated in patients with postzoster neuralgia.

We evaluated the concentration of the neuropeptide somatostatin (SOM) in the CSF of patients with several neurologic diseases. Since SOM is localized in high concentrations in primary sensory pathways, such as the dorsal root ganglia and dorsal horn of the spinal cord, it might be involved in conditions of chronic pain due to functional alterations of nociceptive neurons, such as postinfectious zoster neuralgia. Our study indicated a marked elevation of SOM in patients suffering from postzoster neuralgia compared with controls. Comparison with other neurologic diseases revealed decreased CSF SOM levels in Parkinson's and Alzheimer's disease, unchanged values in patients with amyotrophic lateral sclerosis, and increased concentrations in patients with brain tumors. In neurodegenerative disorders, SOM levels in CSF seemed to reflect the anatomic distribution as well as a reduction or preservation of the peptide in certain brain areas affected by the disease process. In postzoster patients, postinfectious degeneration of dorsal root ganglia cells might cause deafferentation of dorsal horn neurons and activation of SOM-containing systems with increased release either locally from neurons in the dorsal horn of the spinal cord or from descending fiber projections. The results suggested that SOM may take part in the modulation of nociceptive responses.

Herpes Zoster↗

Co-localization of choline acetyltransferase and postsynaptic glycine receptors in motoneurons of rat spinal cord demonstrated by immunocytochemistry.

Male rats were perfused with paraformaldehyde and picric acid. The cervical spinal cord was cryosectioned and immunostained with a monoclonal antibody against the postsynaptic receptor for the neurotransmitter glycine. The anterior horn contained glycinoceptive neurons of varying morphology. Cholinergic cells were identified in the same tissue sections when subsequently immunostained with a monoclonal antibody against choline acetyltransferase, the biosynthetic enzyme of acetylcholine. Immunoreactivity for the glycine receptor was detected in the plasma membrane and for choline acetyltransferase in the perikaryal cytoplasm of identical anterior horn cells, classified as small, medium and large motoneurons. This suggests that motoneurons have receptors for glycine on their cell surface.

Animals↗

Is motilin a cerebellar peptide in the rat? A radioimmunological, chromatographic and immunohistochemical study.

Motilin was demonstrated by the immunoperoxidase technique in endocrine cells of the gastrointestinal tract using several specific antisera. Motilin-like immunoreactivity could only be demonstrated with one of these antisera and was observed in Purkinje cells and dendrites of the cerebellum, in pyramidal cells and dendrites of the cerebral cortex and in dendrites of the CA 3 field of the hippocampus of the rat. Very low motilin-like immunoreactivity was found in cerebellum as well as in cerebral cortex using radioimmunoassay. However, using reverse phase liquid chromatography combined with UV-detection and radioimmunoassay, no peak of a peptide corresponding to synthetic motilin was detectable in rat cerebellar extracts, in contrast to findings in rat duodenum. The results do not suggest that motilin is an intrinsic neuroactive substance of the cerebellum.

Animals↗

Substance P-immunoreactive neurons in the brainstem of the cat related to cardiovascular centers.

The distribution of substance P-immunoreactivity (SP-IR) in the brainstem and spinal cord of normal and colchicine-pretreated cats was analysed using the peroxidase-antiperoxidase (PAP) technique. Numerous SP-IR fibers are present in the nucleus solitarius, nucleus dorsalis nervi vagi and nucleus spinalis nervi trigemini, various parts of the formatio reticularis, substantia grisea centralis mesencephali, locus coeruleus and nucleus parabrachialis. SP-IR perikarya occur in the substantiae gelatinosa and intermedia of the spinal cord, the nucleus spinalis nervi trigemini-pars caudalis, the nucleus dorsalis nervi vagi, and the nucleus solitarius, as well as in the adjacent formatio reticularis and the medullary nuclei of the raphe. In addition, SP-IR cell bodies are located in the nuclei raphe magnus and incertus, ventral and dorsal to the nucleus tegmentalis dorsalis (Gudden), nucleus raphe dorsalis, substantia grisea centralis mensencephali, locus coeruleus, nucleus parabrachialis and colliculus superior. The results indicate that SP-IR neurons may be involved in the regulation of cardiovascular functions both at the central and peripheral level. A peripheral afferent portion seems to terminate in the nucleus solitarius and an efferent part is postulated to originate from the nucleus dorsalis nervi vagi and from the area of the nuclei retroambiguus, ambiguus and retrofacialis.

Animals↗

Somatostatin-like immunoreactivity in non-pyramidal neurons of the human isocortex.

The distribution of somatostatin-immunoreactive cell bodies and axons throughout the human isocortex and subjacent white matter was examined. Vibratome sections of cortical tissue (30-40 micrometers thick) obtained at surgery were treated to reveal the antigen by the unlabelled antibody enzyme method. Two types of somatostatin-immunoreactive axons were present: short, coiled axons and extended ones that follow a straight course in various directions. Somatostatin immunoreactive nerve cell bodies were encountered in layers II-VI and in the subjacent white matter. The majority of labelled cells were found in the white matter and layer VI, and then in layers II and III. The immunoreactive perikarya were fusiform, triangular or multipolar in shape and did not show preferential orientation of their long axis. Frequently, the fusiform neurons in layer VI and in the white matter were aligned parallel to radiate bundles of myelinated fibres. The immunoreactive neurons gave rise to a few thick dendrites. Often thin axon-like processes could also be recognized, originating either from the cell body or from a thicker dendrite. After destaining of the chromogen and counterstaining with aldehydefuchsin and gallocyanin chromealum, the formerly immunoreactive neurons displayed a light and eccentrically located nucleus. The soma contained only a sparse amount of basophilic substance and was nearly devoid of lipofuscin granules. In electron micrographs, the cisterns of the rough endoplasmic reticulum (RER) were localized near the periphery of the soma. Immunoreactivity occurred along membranes of the RER cistern, outer mitochondrial membrane, and in particles 120-150 micrometers in diameter. Rounded areas (up to a diameter of 1 micrometer) lacked immunoreactivity. Furthermore, there were a few tiny lysosomes.

Adult↗