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Biomedical subjects

C Köhler

Publications and source records attributed to C Köhler.

At least 109 records · Page 6Linked to original sources
PubMed1987

Lymphocytic plasmocytoid lymphoma with a three-banded gammopathy: reactivity of one of these paraproteins with cytomegalovirus.

We report the case of a 70-year-old woman suffering from small lymphocytic, plasmocytoid lymphoma with abdominal lymphomas and infiltration of the lung and the bone marrow. A three-banded, IgG lambda, IgM lambda and IgA lambda-paraproteinemia was determined using immunofixation. Because of the patient's high antibody titre against cytomegalovirus (CMV), the possible reactivity of these paraproteins with CMV was studied. The immunoglobulins were transferred to nitrocellulose sheets by a contact diffusion blotting system. CMV was applied to these sheets and the IgG lambda-paraprotein was shown to bind CMV. The reactivity of only one of the paraproteins with CMV suggests an oligoclonal origin of this gammopathy. In addition to the malignant disease an abnormal immune response to a CMV infection could be the cause of this three-banded gammopathy.

Aged↗
PubMed1987

Distribution of [3H]cholecystokinin octapeptide binding sites in the hippocampal region of the rat brain as shown by in vitro receptor autoradiography.

The distribution of binding sites for the neuropeptide cholecystokinin octapeptide in the rat hippocampal region was studied by using quantitative in vitro receptor autoradiography. Biochemical analysis of [3H]cholecystokinin octapeptide binding to tissue sections of the hippocampal region showed it to be of high affinity, to be saturable and approximately 50% specific at saturating concentrations. The binding of [3H]cholecystokinin octapeptide to hippocampal sections was dose-dependently blocked by cholecystokinin octapeptide, cholecystokinin and by pentagastrin. The autoradiographic analysis showed high densities of [3H]cholecystokinin octapeptide binding sites in the hilus of the area dentata, the outer three layers of the retrosplenial area and the presubiculum, layer 3 of the medial, but not the lateral, entorhinal area and the deep and superficial parts of layer 1 and 2, respectively of both the medial and the lateral entorhinal area. Medium binding densities were found in the parasubiculum and remaining layers of the entorhinal area and low densities occurred in the subiculum and in all subfields of Ammon's horn. The angular bundle and fornix-fimbria lacked specific [3H] cholecystokinin octapeptide binding sites. A very similar pattern of binding densities was found for [3H]pentagastrin. Comparisons of the cholecystokinin octapeptide receptor distribution with the cholecystokinin octapeptide innervation of the hippocampal region suggest that there exists a relatively good concordance in some hippocampal subfields such as the presubiculum and the entorhinal area between binding sites for [3H]cholecystokinin octapeptide and cholecystokinin-immunoreactive afferent input.

Animals↗
PubMed1987

Quinolinic acid phosphoribosyltransferase: preferential glial localization in the rat brain visualized by immunocytochemistry.

The excitotoxic brain metabolite quinolinic acid has been hypothetically linked to the pathogenesis of neurodegenerative disorders. By using antibodies prepared against a homogeneous preparation of its catabolic enzyme, quinolinic acid phosphoribosyltransferase [QPRTase; nicotinate-nucleotide:pyrophosphate phosphoribosyltransferase (carboxylating), EC 2.4.2.19], immunocytochemical methods were applied to assess the cellular and subcellular localization of quinolinic acid in the rat brain. On the light-microscopic level, the enzyme was found to be preferentially associated with glial elements of variable morphology. In addition to its presence in glial cells, QPRTase was contained in tanycytes and ependymal cells of the cerebral ventricles and, sporadically, in neurons. Overall, QPRTase immunoreactivity was noted in every brain region studied, the histological pattern being in good accordance with the regional variation of enzyme activity established in biochemical studies. As judged on the ultrastructural level, QPRTase, in all cell types examined so far, was often noted in densely stained roundish cytoplasmic bodies (0.1-0.8 micron in diameter), which were bounded by a single membrane. In functional terms, these structures may represent early lysosomes, secretory granules, or residual bodies. The particular anatomical arrangement of the quinolinic acid system may reflect the brain's defense strategy against detrimental effects of the endogenous excitotoxin.

Animals↗
PubMed1987

Rat 3-hydroxyanthranilic acid oxygenase: purification from the liver and immunocytochemical localization in the brain.

3-Hydroxyanthranilic acid oxygenase (3HAO; EC 1.13.11.6), the biosynthetic enzyme of the endogenous excitotoxin quinolinic acid, was purified to homogeneity from rat liver and partially purified from rat brain. The pure enzyme is a single subunit protein with a molecular weight of 37-38,000. Kinetic analyses of both pure liver and partially purified brain 3HAO revealed an identical Km of 3 microM for the substrate 3-hydroxyanthranilic acid. Evidence for the identity of liver and brain 3HAO was further provided by physicochemical (electrophoretic behavior, heat sensitivity) and biochemical (pH dependency, activation by Fe2+) means. Antibodies were produced against the pure liver enzyme and the identity of liver and brain 3HAO substantiated immunologically in immunotitration and Ouchterlony double-diffusion experiments. Immunohistochemical studies using purified anti-rat 3HAO antibodies were performed on tissue sections of perfused brains and demonstrated a preferential staining of astroglial cells. Notably, the cellular localization of 3HAO in the brain appears to be in part distinct from that of quinolinic acid phosphoribosyltransferase, the catabolic enzyme of quinolinic acid. Pure rat 3HAO and its antibodies can be expected to constitute useful tools for the further elucidation of the brain's quinolinic acid system.

3-Hydroxyanthranilate 3,4-Dioxygenase↗
PubMed1987

The "erythrocyte receptor" of T-lymphocytes and T11 target structure (T11TS): complementary cell interaction molecules involved in T-cell activation.

The CD2 or T11 glycoprotein on T-lymphocytes is the receptor for both sheep and human erythrocytes in the formation of spontaneous ("E"-)rosettes. Recent evidence employing monoclonal anti-T11 antibodies suggested that T11 is also a signal transducing molecule with a function in T-cell activation. The present report summarizes the identification of T11 target structure (T11TS), a natural ligand of T11, and its biochemical and functional characterization. T11TS is defined by a mAb to sheep erythrocytes that completely blocks their binding to CD2. It is a glycoprotein of 42 kDa MW expressed on all types of blood cells and some other tissues. While the anti-T11TS mAb used is specific for sheep cells, an antiserum raised to purified T11TS also blocks human autologous E-rosetting. Evidence is presented that the human lymphocyte function associated antigen (LFA)-3, which had recently been shown to be the likely human ligand of CD2, is the structural and functional human homologue of T11TS. Functional studies on T-cell activation employing sheep erythrocytes as one ligand of CD2 indicate that binding of T11TS to the E-receptor provides one of the signals required for T-cell activation through the CD2 molecule.

Animals↗
PubMed1986

Distribution of serotonin-1A receptors in the monkey and the postmortem human hippocampal region. A quantitative autoradiographic study using the selective agonist [3H]8-OH-DPAT.

Serotonin-1A receptors were visualized and their anatomical distribution mapped within the monkey and the human hippocampus by using in vitro receptor autoradiography of the selective agonist [3H]8-OH-N,N-dipropyl-2-aminotetralin ([3H]8-OH-DPAT). The results show high densities of serotonin-1A receptors heterogeneously distributed in different subfields and layers of the monkey and the human hippocampal region. High densities are found in the molecular layer of area dentata, all layers of regio superior and the subiculum, parasubiculum, and layers 2, and 4 through 6 of the entorhinal area. In the human hippocampus, a distinct band of [3H]8-OH-DPAT binding sites is present in the subgranular zone of the area dentata. The similar anatomical distribution of [3H]8-OH-DPAT binding sites in the monkey and the human hippocampal region suggests that the serotonin-1A receptor is phylogenetically well preserved and indicates that this receptor may mediate action(s) of serotonin in the primate, including the human hippocampal region.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1986

Galanin immunoreactivity in hypothalamic neurons: further evidence for multiple chemical messengers in the tuberomammillary nucleus.

By using a specific antibody against the 29 amino-acid peptide galanin (Gal) with light and electron microscopic immunocytochemistry, we have studied the distribution of Gal immunoreactivity in the posterior hypothalamic magnocellular neurons of the rat. In colchicine-treated rats, a large number of Gal-immunoreactive cells were identified within all subdivisions of the tuberomammillary nucleus. The majority of these cells are large multipolar or fusiform neurons, with long, sparsely branching dendrites. A small number project to the ventral hippocampus, as shown by experiments with the retrograde tracing of Fast Blue. Ultrastructural examination of the Gal-immunoreactive cells confirms their indentity as magnocellular neurons, with dense deposits of immunoreaction product, particularly in small ribosomal arrays and in large, dense-cored vesicles. Axosomatic synapses occur on these neurons. The axonal boutons synapse with asymmetric and symmetric junctions and contain small synaptic vesicles as well as numerous large, dense-cored vesicles, which display Gal immunoreactivity. Sequential staining of thin, alternate sections with antibodies against Gal and L-histidine decarboxylase (HDCase; EC 4.1.1.22) showed colocalization of Galand HDCase-immunoreactivities in a majority of tuberomammilary neurons. The finding of Gal immunoreactivity within histamine-producing neurons of the tuberomammillary nucleus adds to the multiplicity of potential neuronal messengers utilized by these cells.

Animals↗
PubMed1986

Distribution of neurons and axons immunoreactive with antisera against neuropeptide Y in the normal human hippocampus.

The detailed distribution of neuropeptide tyrosine (neuropeptide Y; NPY) immunoreactive neurons and fibers is given for the normal human hippocampus. These neuronal elements are detected by a polyclonal antibody raised against the unconjugated peptide and controls were obtained by using liquid phase absorption immunocytochemistry. The description covers the distribution in the area dentata, the hippocampal subfields CA3 and CA1, the subicular complex, and the entorhinal area. Each region is distinct in its NPY content. In general, the hippocampal NPY immunoreactive neurons fall into distinct classes--large hilar neurons; cortical small bipolar or bitufted neurons; medium-sized multipolar neurons in the deep cortical layers; and finally the distinct, small bipolar NPY neurons of the white matter bundles. None of the NPY neurons are pyramidal; many are likely to be local circuit neurons, but some appear to have extrinsic connections. The NPY immunoreactive axonal innervation is dense throughout the hippocampus but shows distinct regional differences in the hippocampal subdivisions. The area dentata has hilar NPY immunoreactive neurons and radial varicose fibers scattered throughout without a clear laminar preference. Subfield CA3 is comparatively the weakest NPY-containing region and contrasts with CA1, which is well endowed with reactive neurons and a rich and unusual axonal innervation, with distinct laminar axonal specializations. The subicular complex is well endowed with cells and fibers and the parasubiculum consistently displays unusually heavy NPY innervation. The entorhinal area exhibits a rich cortical distribution pattern, like that previously described for the human cerebral cortex (Chan-Palay et al; J. Comp. Neurol. 238:382-390, '85a,b). The fimbria, alveus, and angular bundle have NPY neurons embedded within the white matter. Like the NPY immunoreactive innervation of the hippocampal regions of laboratory animals, the human NPY innervation seems to follow a common fundamental pattern with respect to cell locations, cell morphology, and axonal innervation. The difference, however, is the greater complexity and profusion of the NPY-immunoreactive axonal plexuses in the human hippocampus. This rich peptide network within the hippocampus with likely extrahippocampal interconnections raises questions concerning coexistence with other neuroactive substances, the functions of such substantial networks, and how they are altered in human neurological disease.

Aged↗
PubMed1986

Distribution of altered hippocampal neurons and axons immunoreactive with antisera against neuropeptide Y in Alzheimer's-type dementia.

This paper provides detailed information on the distribution of neuropeptide tyrosine (neuropeptide Y; NPY) immunoreactive neurons and fibers in the hippocampal region of eight neuropathologically confirmed cases of Alzheimer's-type dementia (ATD) at postmortem. These neuronal networks are detected by a polyclonal antibody raised against the unconjugated peptide and controls were obtained by using liquid phase absorption immunocytochemistry. The description covers the subfields area dentata, CA3 and CA1, the subicular complex, and the entorhinal area. The hippocampal regions in which the NPY-i neuron networks are most severely affected are the hilus, CA1, the parasubiculum, and the entorhinal cortex. Less obvious reductions occurred in CA3, subiculum, and the presubiculum. Parallel semiquantitative estimates were made of the numbers of neuritic plaques and neurofibrillary tangles in the other hippocampus of the brains in every ATD case. The areas of heaviest pathological changes by these indices are CA1 and the entorhinal cortex. The subicular complex CA3 and the area dentata are less affected. These findings show that the areas with the most severe loss of NPY-i neurons and axons, CA1 and the entorhinal cortex, are the same as those areas most severely affected by the other indices of ATD. Thus NPY-i networks are involved in the ATD disease process. However, other NPY-i networks survive, in some subfields better than in others. The cumulative evidence suggests a population of hippocampal peptide neurons that are remarkably resistant in terminal neurological disease. These neurons have the capability to participate in the maintenance of minimal functioning circuits in target areas of the disease and as such hold significant links for our understanding of synaptic plasticity in disease.

Aged↗
PubMed1986

Autoradiographic visualization of dopamine D-2 receptors in the monkey brain using the selective benzamide drug [3H]raclopride.

Using the novel substituted benzamide drug [3H]raclopride in combination with in vitro receptor autoradiography, the distribution of dopamine D-2 receptors was studied in the monkey brain. Highest densities of D-2 receptors are present in dopamine-rich areas and the distribution shows the following rank order: caudatus and putamen greater than nucleus accumbens greater than olfactory tubercle greater than substantia nigra (pars compacta) greater than insular cortex greater than piriform and entorhinal cortex greater than substantia nigra (pars reticulata). In all of these areas [3H]raclopride binding was blocked by dopamine (1 microM) and by D-2 receptor antagonists such as (+)-butaclamol, eticlopride and raclopride, while the D-1 receptor antagonist SCH 23390 (1 microM) reduced [3H]raclopride binding by 15-20% in some restricted parts of the caudatus and putamen exclusively.

Animals↗
PubMed1986

Origin of the neuropeptide Y innervation of the rat retrohippocampal region.

Using the method of retrograde tracing of Fast Blue in combination with immunohistochemistry, the origins of the retrohippocampal neuropeptide Y (NPY) innervation was studied in the rat brain. The findings suggest that two NPY-immunoreactive (NPY-i) afferent systems, one intrinsic and the other of extrinsic origin give rise to the massive NPY innervation of the retrohippocampal region, including the entorhinal area (EA). The intrinsic projections originate from multipolar and fusiform cells situated primarily in layers IV through VI of the medial and lateral EA, as well as from a small number of NPY-i basket cells situated in layer II. Other NPY-i afferents originate from cortical neurons with long association projections located in the deep layers of the perirhinal area and in the piriform cortex, as well as from cells situated throughout the rostrocaudal extent of the endopiriform nucleus, in the lateral nucleus of amygdala and in the nucleus locus coeruleus.

Amidines↗
PubMed1986

Intrinsic connections of the retrohippocampal region in the rat brain. II. The medial entorhinal area.

The present study describes the efferent projections and terminal distributions within the retrohippocampal region of individual layers of the rat medial entorhinal area (MEA) as studied by the methods of anterograde transport of the lectin Phaseolus vulgaris leucoagglutinin (PHA-L) and retrograde transport of the fluorescent dye Fast Blue (FB). Analysis of the PHA-L injections that were relatively well restricted to single layers of the MEA reveals very sparse projections to the parasubiculum, presubiculum, and subiculum, while numerous projections within the MEA are found. The course and the termination of the intra-entorhinal projections differ depending upon the particular layer under study, and marked differences are found between the deep and the superficial layers in terms of the divergence of their respective projections. However, the general intra-entorhinal orientation of these projections is essentially the same for all layers: longitudinal with a slightly oblique course, such that at ventral levels the center of a particular terminal field is always located lateral to the center of the respective PHA-L injection. PHA-L injections into layer II label axons running horizontally within this layer as well as within the deep part of layer I, and PHA-L injections into the medial sector of layer II reveal horizontal projections that innervate most of the second layer. The horizontal projections of layer III are more restricted than those of layer II but both layer II and III have prominent longitudinal projections directed ventrally. From layers II and III, numerous axons project to the deep layers (IV-VI) probably en route to extra-entorhinal structures, since no major terminal fields were detected in the deep layers. The PHA-L and the FB experiments show that the deep layers (in particular IV and VI) have far more divergent intra-entorhinal projections than have layers II and III. PHA-L injections into layers IV, V, and VI reveal widespread efferent projections to all of the more superficially located layers of the MEA in addition to projections to the lateral EA. The retrograde transport studies show that layers IV and VI are the major sources of these divergent projections and that cells situated throughout the entire medial to lateral width of these layers project to every sector of the retrohippocampal region. Taken together, the findings of the present experiments suggest that (1) all layers of the MEA have longitudinal projections directed primarily toward the ventral (or temporal) part of this cortex, (2) the projections of layers II and III are relatively restricted compared of the deeper layers.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Neuropeptide Y innervation of the hippocampal region in the rat and monkey brain.

Using antibodies to neuropeptide Y (NPY) in combination with immunohistochemical techniques we have studied the distribution of cell bodies and nerve terminals containing NPY immunoreactivity (-i) in the hippocampal region of rats and monkeys (cynomolgus). In colchicine-pretreated rats a large number of NPY-positive cells are present in all areas of the hippocampal region. The NPY-i cells range in size from small (diameter across soma: 10-15 micron) to large (approximately 20 micron). Most of the NPY-i cells are situated in the hilus, in the subgranular zone of the area dentata, and in the stratum oriens of Ammon's horn. A majority of these are polymorphic cells but cells of different morphology are present in these layers as well. These include small spheroid cells and dentate pyramidal basket cells that are distinct from the polymorphic cells in the subgranular zone. The subicular complex (e.g., the subiculum, pre-, and parasubiculum) and the entorhinal area contain fewer NPY-i cells than the rest of the hippocampal region. In the dorsal parts of the pre- and parasubiculum numerous small cells are scattered throughout all layers, while in the entorhinal area the NPY-stained cells are situated primarily in the deep layers (V and VI). In the ventral part of the lateral entorhinal area large multipolar and bitufted cells are found in layers II-VI. In the untreated monkey brain NPY-positive cells are found in the hilus of the area dentata and in the deep (IV through VI) layers of both the medial and lateral entorhinal area. Fewer NPY-stained cells are present in the subicular complex and in the entorhinal area. In the monkey as well as in the rat, NPY-stained cells are present in the angular bundle and in the alveus. A dense network of NPY-i fibers innervates the entire hippocampal region in both the rat and the monkey. The hippocampal NPY-i preterminal processes are present primarily in stratum moleculare of Ammon's horn and in the outer one-third of this layer in the area dentata. The NPY-positive innervation of the dentate molecular layer is far more prominent in the monkey than in the rat brain. Numerous NPY-stained fibers are scattered in other areas as well. In all retrohippocampal structures, and in particular the entorhinal area, the NPY-i fibers form a massive network that innervates all layers to about the same extent, with the exception of the molecular layer, which is more densely innervated than the other layers.

Animals↗
PubMed1986

Regional in vivo binding of the substituted benzamide [3H]eticlopride in the rat brain: evidence for selective labelling of dopamine receptors.

The novel substituted benzamide eticlopride, (S)-(-)-5-chloro-3-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-methoxy salicylamide hydrochloride (A38503; FLB 131), was radiolabelled to high specific activity and used for in vivo receptor binding studies in the rat brain. Intravenous injections of [3H]eticlopride resulted in a rapid accumulation of radioactivity in several brain regions: striatum greater than olfactory tubercle greater than septum greater than substantia nigra greater than frontal cortex greater than cerebellum. Approximately 95% of the radioactivity recovered from the striatum was in the form of authentic eticlopride, as determined by thin-layer chromatography. Two hours after injection, the ratio between the amount of radioactivity present in the striatum and in the cerebellum was approximately 10:1. The in vivo binding of [3H]eticlopride was saturable in all dopamine-rich areas, with a very low proportion of non-specific binding. The specific in vivo binding of [3H]eticlopride was blocked by several dopamine antagonists, including haloperidol, (+)-butaclamol, spiperone, d,l-sulpiride and remoxipride. The dopamine agonist N-n-propylnorapomorphine, but not apomorphine, was found to be a potent blocker of in vivo [3H]eticlopride binding. Serotonin and noradrenaline receptor antagonists did not prevent the in vivo binding of [3H]eticlopride. Autoradiographic analysis of the in vivo [3H]eticlopride binding showed a high density of binding sites in the striatum, nucleus accumbens and the olfactory tubercle. Moderate binding was found in the hippocampal formation and in the entorhinal area, but little or no binding was detected in other cortical regions. [3H]Eticlopride binding in all these areas was blocked by pretreatment with (+)-butaclamol. Taken together, these findings show that the substituted benzamide compound [3H]eticlopride passes readily into the brain and binds with high specificity to dopamine or neuroleptic receptors in dopamine-rich brain areas. Thus, eticlopride may be a useful tool in studies of dopamine D-2 receptors in vivo.

Animals↗
PubMed1986

T11TS, the cell surface molecule binding to the "erythrocyte receptor" of T lymphocytes: cellular distribution, purification to homogeneity and biochemical properties.

T11 target structure (T11TS) is a sheep cell surface glycoprotein that binds to the E receptor of human and sheep T lymphocytes. Here we report that T11TS has a broad tissue distribution, including mature and immature hematopoietic cells, vascular endothelium and smooth muscle. The density of T11TS expression was determined by Scatchard analysis with radiolabeled anti-T11TS monoclonal antibody. Red blood cells bound 10,000, and leukocytes bound 4000 to 23,000 antibody molecules per cell. T11TS was purified to homogeneity by immune-affinity and preparative sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and some of its biochemical properties were determined. T11TS is an acidic (pI 4.5) membrane glycoprotein that binds to concanavalin A. It has 2 or 3 N-glycosidically linked carbohydrate side chains of the mature phenotype, no O-linked sugars, and an apparent mol. mass of 42 kDa (glycosylated) and 32 kDa (deglycosylated). The anti-T11TS monoclonal antibody L180/1, which blocks binding of sheep red blood cells to CD2, recognizes a protein determinant on T11TS. These findings are discussed with respect to the possible function of the CD2-T11TS system as a set of complementary cell interaction molecules involved in T cell activation.

Antibodies, Monoclonal↗
PubMed1986

Quinolinic acid: a pathogen in seizure disorders?

The evidence for an involvement of QUIN in human seizure disorders is clearly circumstantial. Importantly, QUIN is not a classical neurotransmitter and may thus play only a negligible or no role at all in normal brain function (Foster et al., 1984). We have yet to understand if and how such a possibly inert metabolite may turn into a pathogen. Several crucial questions remain to be addressed before a case can be made for a 'quinolinic acid hypothesis' of temporal lobe epilepsy. Among the most prominent ones figure the extracellular concentration of QUIN in the human brain under normal and pathological ('epileptic') conditions, the relationship between QUIN metabolism in the brain and its extracellular concentration and, a related issue, the regulation of cerebral QUIN metabolism (i.e., turnover). It is of equal importance to assess if NMDA-receptors, particularly those in the hippocampus and other parts of the limbic system, can exert a modulatory function upon brain QUIN. Unquestionably, future experiments with selective NMDA-antagonists will prove useful for the elucidation of such possible (feedback) interactions.

Afferent Pathways↗