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C Köhler

Publications and source records attributed to C Köhler.

At least 73 records · Page 4Linked to original sources
PubMed1991

GABA-like immunoreactivity in the tuberomammillary nucleus: an electron microscopic study in the rat.

The organization of GABAergic elements in the histaminergic tuberomammillary nucleus has been examined by using antibodies against gamma-aminobutyric acid (GABA) and light and electron microscopy. Most neuronal perikarya of the ventral subgroup of the tuberomammillary nucleus were GABA immunoreactive (GABA-i). The morphology of the GABA-i perikarya was similar to the morphology of histaminergic perikarya described by Hayashi et al. ('84: J. Comp. Neurol. 229: 223-241) and Wouterlood et al. ('86: J. Comp. Neurol. 252:227-243). The GABA-i perikarya were contacted by relatively few terminals. The mean bouton covering ratio of GABA-i perikarya was 6.1%, whereas the mean bouton covering ratio for GABA-i dendrites in the tuberomammillary nucleus was 31%. Some of the presynaptic terminals were GABA-i. In addition, GABA-i perikarya and dendrites formed close contacts that never presented synaptic specializations. These results suggest that neurons of the histaminergic tuberomammillary nucleus contain the neurotransmitter GABA. Furthermore, GABA may act as a modulator of cellular processes within the tuberomammillary nucleus.

Animals↗
PubMed1991

NCQ 298, a new selective iodinated salicylamide ligand for the labelling of dopamine D2 receptors.

NCQ 298 ((S)-3-iodo-N-[(l-ethyl-2-pyrrolidinyl)methyl]-5,6- dimethoxysalicylamide) has an iodine substituent. We have labelled NCQ 298 with 123I and 125I, and used the radioligands as tracers in receptor studies in vitro, in vivo in autoradiography and in SPECT studies on Cynomolgus monkeys. [125I]NCQ 298 bound in vitro to a single binding site with a KD = 19 pM. NCQ 298 has thus a 10-fold higher affinity for the dopamine D2 receptors than the corresponding des-5-methoxy compound FLA 961 (IBZM), previously used in SPECT studies. The binding of [125I]NCQ 298 was entirely reversible (T1/2 = 17.5 min at 37 degrees C). Autoradiographical studies in vitro on rat and monkey brain tissue sections showed a distinct binding in caudate-putamen, nucleus accumbens, substantia nigra, and in layer 5 of the cerebral cortex. In vivo binding studies in mice showed a ratio of 10 between [125I]NCQ 298 binding in striatum and cerebellum. Binding was displaced by the selective dopamine D2 receptor antagonist raclopride. In SPECT studies with [123I]NCQ 298 in two Cynomolgus monkeys, radioactivity accumulated in the basal ganglia. The measured striatum to cerebellum ratio was about 15 after 3 h. A monkey brain phantom was constructed for the determination of conversion factors from pixel events to actual radioactivity. The resulting, corrected striatum to cerebellum ratio obtained was 30. After administration of 12 mg raclo-pride to one of the monkeys there was a substantial decrease in striatal radioactivity. [125I]NCQ 298 is a suitable ligand for the labelling of dopamine D2 receptors in vitro and in vivo. The specific properties of [123I]NCQ 298 suggest that this compound is a useful ligand for quantitative SPECT studies of dopamine D2 receptors in man.

Animals↗
PubMed1991

Immunohistochemical localization of quinolinic acid phosphoribosyltransferase in the human neostriatum.

The localization and distribution of quinolinic acid phosphoribosyltransferase, the degradative enzyme of the endogenous excitotoxin quinolinic acid, were studied in the post mortem human neostriatum by immunohistochemistry. In eight neurologically normal human brains, quinolinic acid phosphoribosyltransferase immunoreactivity was detected in both glial cells and neurons. Typically, glial cells containing quinolinic acid phosphoribosyltransferase immunoreactivity had numerous processes radiating from the cell bodies. In Nissl-counterstained sections, most quinolinic acid phosphoribosyltransferase-immunoreactive glial cells showed round, large and pale nuclei. These morphological features indicate that they are probably astrocytes. Neurons containing quinolinic acid phosphoribosyltransferase immunoreactivity had different sizes and shapes and were tentatively classified into three subpopulations. Most were medium-sized cells with ovoid or elongated perikarya. Small quinolinic acid phosphoribosyltransferase-immunoreactive neurons, often spheroid in shape, were particularly noted in a zone of the caudate nucleus adjacent to the lateral ventricle. A few large quinolinic acid phosphoribosyltransferase-positive neurons were also present in both the caudate and putamen. The somatic and dendritic morphology of quinolinic acid phosphoribosyltransferase-immunoreactive neurons closely resembles that of aspiny neurons seen in Golgi preparations. The localization of the specific quinolinic acid-catabolizing enzyme in distinct populations of neostriatal cells suggests specific functional correlates. It remains to be examined how the anatomical organization of quinolinic acid phosphoribosyltransferase immunoreactivity relates to the degradation of quinolinic acid in the striatum, and if the morphological characteristics and distribution of quinolinic acid phosphoribosyltransferase-immunoreactive cells are of relevance for the pathogenesis of neurodegenerative basal ganglia disorders.

Adult↗
PubMed1991

Short-term radiotherapy as palliative treatment in patients with transitional cell bladder cancer.

We report the results and complications of treatment with palliative, short-term radiotherapy in 162 elderly or disabled patients. Improvement in tumour-associated symptoms was noted in 75 of these patients and 72 survived for more than a year. Those who responded to radiotherapy had a 5-year cancer-free survival rate of 58% compared with 4% in patients who did not respond to treatment. Survival was also affected by stage and indications for radiotherapy. In 85 patients without severe symptoms, where the tumour was judged curable but the patient was unsuitable for a full course of radiotherapy, the 5-year cancer-free survival rate was 21%, which is in accordance with what can be achieved with full-course radiotherapy; 42% had various minor acute side effects. The 5-year late complication rate was 7%.

Aged↗
PubMed1990

Galanin receptors in the post-mortem human brain. Regional distribution of 125I-galanin binding sites using the method of in vitro receptor autoradiography.

The distribution of putative receptors for the peptide galanin was studied in the normal post-mortem human brain by using 125I-galanin (0.5 nM) in combination with in vitro receptor autoradiography. Specific binding of 125I-galanin was found in a large number of brain areas throughout the neuraxis. Highest binding densities occurred in the basal forebrain and hypothalamus, while the basal ganglia, major parts of the thalamus and the tectum were found to be poor in binding sites. All cortical areas harboured 125I-galanin binding, and in the visual cortex a laminated pattern was present. In the hippocampus, 125I-galanin binding occurred in layer 2 of the entorhinal cortex, in the uncus and in the hippocampal-amygdala area. In the brain-stem, 125I-galanin binding was found in serotoninergic noradrenergic cell groups as well as in the reticular formation and in the parabrachial nuclei. Galanin receptors may, thus, mediate the response of galanin in numerous structures in the human brain.

Aged↗
PubMed1990

Distribution of quinolinic acid phosphoribosyltransferase in the human hippocampal formation and parahippocampal gyrus.

The morphological distribution of quinolinic acid phosphoribosyltransferase (QPRT), the degradative enzyme of the endogenous excitotoxin quinolinic acid, was studied in the human hippocampal formation and parahippocampal gyrus by immunohistochemical techniques. In seven neurologically normal human brains obtained at autopsy, QPRT-immunoreactivity (QPRT-i) was found in both glial cells and neurons. Glial cells exhibiting QPRT-immunoreactivity morphological features of astrocytes, were observed in all hippocampal subfields. The polymorphic layer of the dentate gyrus contained the highest density of QPRT-i glial cells. Numerous QPRT-i glial cells were also found along both sides of the fused hippocampal fissure and in the white matter including the alveus of Ammon's horn, whereas only a few were observed in the granule cell layer and the stratum pyramidale. Neurons containing QPRT-i were found mainly in the subiculum and in the strata oriens and pyramidale of CA1. They were mostly small and polymorphic or fusiform, thus indicating that they may belong to a subpopulation of interneurons. Moderate numbers of QPRT-i glial cells and neurons were also observed throughout layers II-VI of parahippocampal cortex. The localization of QPRT-i in selected glial cells and neurons suggests that in the regions examined these cellular elements might play specific roles in the regulation of quinolinic acid function.

Adult↗
PubMed1990

Regional distribution of ethanol-inducible cytochrome P450 IIE1 in the rat central nervous system.

A specific form of cytochrome P450, P450 IIE1, active in ethanol oxidation, is known to be induced about 10-fold in rat liver following ethanol treatment. This isozyme of P450 participates effectively in the metabolic activation of precarcinogens, such as N-dimethylnitrosamines, and of solvents such as carbon tetrachloride and benzene. In the present investigation, two different polyclonal antisera against P450 IIE1 were used in order to map the regional distribution of this P450 form in the rat central nervous system. The presence of P450 IIE1 in various brain regions was confirmed by Western blot analysis. The P450 IIE1-immunoreactivity was heterogeneously distributed between brain areas. Neuronal cell bodies and glial cells of presumed astroglial as well as oligodendroglial identity contained immunoreactivity. All fiber tracts harbored P450 IIE1-immunoreactive glial cells as did the ependymal lining of the ventricular wall as well as small and large vessels throughout the brain. P450 IIE1-immunoreactive glial cells were present in all areas of the neocortex, in the olfactory bulb, in the piriform cortex and in several different thalamic nuclei. In the cerebellum, P450 IIE-immunoreactivity was found in all cell layers and was exclusively localized to glial cells and their processes. Staining of blood vessels was prominent in the white matter where P450 IIE1-immunoreactive glial cells were seen to have end-feet on the vessels. A subgroup of pyramidal cells of the frontal cortex showed strong P450 IIE1-immunoreactivity, as did a component of the olfactory nerve which innervates the accessory bulb. In the hippocampal region, the pyramidal cells of all subfields were P450 IIE1-immunoreactive. Some polymorphic cells of the hilus and subfield CA stained intensely with the P450 IIE1 antibodies. A high density of P450 IIE1-immunoreactivity was detected throughout the striatal complex. The immunoreactivity was localized to neuronal cell bodies as well as the neurophil. Fibers of the nigrostriatal system were strongly P450 IIE1-immunoreactive. Mechanical lesions of this pathway showed an accumulation of P450 IIE1-immunoreactivity proximal to the lesion relative to the striatum and a depletion in the reticular part of the substantia nigra, suggesting that the antigen may be transported from the striatum to the substantia nigra. In the brain stem a high density of P450 IIE-immunoreactive neurons was detected in the substantia nigra, the pontine nucleus, lateral superior olive and the nucleus of the trigeminal nerve and facial nucleus. A great number of large- to medium-sized immunoreactive neurons were situated in the central gray and in the reticular formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1990

Subicular projections to the hypothalamus and brainstem: some novel aspects revealed in the rat by the anterograde Phaseolus vulgaris leukoagglutinin (PHA-L) tracing method.

The efferent projections from the subiculum to the hypothalamus were examined in the rat by using the anterograde PHA-L tract-tracing method. The density of the subicular projections to the hypothalamus increases at successively more ventral levels of the subiculum. The ventral tip of the region projects to the hypothalamus via 3 different routes: the postcommissural fornix, the medial corticohypothalamic tract (mht) and a ventral pathway running via the amygdala. The fibers in the fornix innervate the median subgroup of the mammillary bodies and, through collaterals, also the lateral hypothalamus. Axons innervating the medial preoptic area, anterior hypothalamus, ventromedial and dorsomedial nuclei as well as the median part of the mammillary nucleus run in the mht. The ventral pathway innervates the supraoptic and medial preoptic nuclei as well as the lateral hypothalamus. Taken together, efferents of the ventral subiculum reach most major areas situated along the longitudinal axis of the hypothalamus. Importantly, however, subicular efferents reach beyond the hypothalamus: PHA-L immunoreactive axons were traced into the mesencephalic central gray and medulla. These anatomical findings show that highly processed cortical information may reach hypothalamic and brainstem areas involved in the integration of endocrine and autonomic functions as well as motivated behaviors.

Animals↗
PubMed1990

Comparative analysis of the action of class I antiarrhythmic drugs (lidocaine, quinidine, and prajmaline) in rabbit atrial and ventricular myocardium.

Effects of three class I antiarrhythmic drugs (quinidine, lidocaine, and prajmaline) on transmembrane resting (RMP) and action potentials (AP) of isolated rabbit atrial and ventricular myocardium were studied at different stimulation rates. The frequency-dependent depression of the maximal upstroke velocity (Vmax) of the AP (sodium channel block) was analyzed according to the "guarded receptor" hypothesis. The resting block (Vmax depression after a resting period) induced by prajmaline (10(-6) M), quinidine (2.2 x 10(-5) M), and lidocaine (4.3 x 10(-5) M) was more expressed in the atrium (44, 28, and 19%, respectively) than in the ventricle (32, 9, and 0%, respectively). There were also significant (p less than 0.05) atrioventricular differences in the frequency-dependent extra block (Vmax reduction on stimulation at 3.3 Hz) for quinidine (39 vs. 26%) and lidocaine (4 vs. 25%). From the analysis, according to the guarded receptor hypothesis, it follows that the three compounds bind preferentially to inactivated sodium channels with about the same affinity to the atrium and ventricle, except for quinidine which shows a significantly smaller dissociation constant in the atrium (5 x 10(-6) M vs. 2.7 x 10(-5) M; p less than 0.001). We conclude that the atrioventricular differences in the resting block are mainly due to atrioventricular differences in the RMP, whereas the differences in the frequency-dependent extra block are based on the shorter atrial AP duration (lidocaine) or are due to higher affinity to atrial sodium channels (quinidine).

Action Potentials↗
PubMed1990

Biochemical pharmacology of the atypical neuroleptic remoxipride.

In vitro receptor ligand binding studies in the rat showed that remoxipride displaced different radioligands at the dopamine D2, but not the D1 receptor. Remoxipride did not block dopamine-stimulated adenylate cyclase activity in vitro suggesting that it did not directly interact with the dopamine D1 receptor. Like other antipsychotic compounds, it increased dopamine turnover in the dopamine-rich areas of the brain. It showed no affinity for a wide range of neurotransmitter receptors, with the exception of the opiate sigma receptor. The affinity of remoxipride for the D2 receptor was low in vitro, while in vivo, the affinity was relatively high. Remoxipride was far more potent in preventing [3H]raclopride-binding than [3H]spiperone-binding to the D2 receptor in vivo. When the D2 receptor was labelled with [3H]spiperone, remoxipride was shown to exert a preferential blockade of this binding in extrastriatal areas of the brain (for example, olfactory tubercle, septum, substantia nigra) in vivo. After the injection of high doses of remoxipride most if not all drug in the brain was identified as authentic remoxipride. After injection of [3H]remoxipride in smaller and larger doses, radioactivity was detected in all areas of brain examined, including cerebellum and neocortex. Most of the remoxipride-derived radioactivity was found in the choroid plexus and circumventricular organs, while smaller amounts were recovered in the striatum, olfactory tubercle, and substantia nigra. Taken together, these findings suggest that remoxipride acts at both the central D2 and sigma receptors and that its affinity for the D2 receptor is relatively low in vitro. A regional preference for D2 receptors can be observed in vivo depending upon the radioligand used.

Animals↗
PubMed1990

Syntheses of [123I]-, [125I]- and unlabelled (S)-3-iodo-5,6-dimethoxy-N-[(1-ethyl-2-pyrrolidinyl)methyl]salicylamide (NCQ 298), selective ligands for the study of dopamine D-2 receptors.

The salicylamide NCQ 298, (S)-3-iodo-N-[(1-ethyl-2-pyrrolidinyl)methyl]-5,6-dimethoxysalicylami de (4), binds with a high affinity and selectivity to central dopamine D-2 receptors. In the present paper the synthesis of NCQ 298 and the efficient labelling both with 123I and 125I are described. The unlabelled NCQ 298 was synthesized by iodination of (S)-N-[(1-ethyl-2-pyrrolidinyl)methyl]-2,5,6-trimethoxybenzamide followed by demethylation with boron tribromide, which produced 4 and the regioisomer 5 in a ratio of 82:18. The two isomeric salicylamides were separated by radial chromatography and tested for their abilities to inhibit the binding of [3H]raclopride to rat striatal membranes in vitro in relation to some representative salicylamides. The 5,6-dimethoxysalicylamide 4 (NCQ 298) was found to be considerably more active than the corresponding 6-methoxysalicylamide 10 (FLA 961 or IBZM). The radioligands [123I]NCQ 298 and [125I]NCQ 298 were prepared in a carrier-free form from the corresponding desiodo compound by the chloramine-T protocol and isolated by semipreparative HPLC. The total radiochemical yields of [123I]NCQ 298 and [125I]NCQ 298 (based on [123I]- and [125I]iodide and decay-corrected) were 88% and 93%, respectively, with a radiochemical purity of greater than 99%. [125I]NCQ 298 will be studied to evaluate its potential as a radioligand in studies requiring a high specific activity, selectivity and high potency to label dopamine D-2 receptors. [123I]NCQ 298 has potential as a radioligand for the in vivo examination of central dopamine D-2 receptors in human brain by Single Photon Emission Computed Tomography (SPECT).

Animals↗
PubMed1990

[The loading capacity of different pin-post structural systems].

Compared with semi-individual or individual cast constructions, fully manufactured post-abutment systems are exposed to stronger torsional loads due to their circular cross-sections. The investigations refer to the question, to what extent different manufactured constructions in the root of a tooth will withstand torsional moments. A cold-pressured connection between titanium-post and titanium-construction was tested as to its mechanical load capacity. Moreover, the mechanical compound stability of individual cast constructions on friction-posts was investigated.

Dental Casting Technique↗
PubMed1989

Evidence for the existence of a population of arcuate neurons costoring choline acetyltransferase and tyrosine hydroxylase immunoreactivities in the male rat.

By combined immunoperoxidase and immunofluorescence histochemistry we have analyzed the distribution of choline acetyltransferase (ChAT) and tyrosine hydroxylase (TH) immunoreactive (IR) perikarya within the same sections of the mediobasal hypothalamus of the male rat. Evidence was obtained for the existence of perikarya costoring TH and ChAT immunoreactivities in both the dorsomedial and ventrolateral part of the arcuate nucleus and in the adjacent periarcuate nucleus at all rostrocaudal levels. The results strongly implicate interactions between dopamine and acetylcholine as well as acetylcholine and growth hormone releasing factor in dorsomedially and ventrolaterally located TH/ChAT costoring tuberoinfundibular neurons, respectively.

Animals↗
PubMed1989

Brainstem afferents to the tuberomammillary nucleus in the rat brain with special reference to monoaminergic innervation.

Monoaminergic innervation of a histamine-producing cell group, the tuberomammillary nucleus in the posterior hypothalamus, was investigated in the rat by light and electron microscopic immunohistochemical techniques. Immunohistochemical staining of sections of the posterior hypothalamus was demonstrated afferent fibers immunoreactive to tyrosine hydroxylase in ventral and medial subgroups of the tuberomammillary nucleus afferent fibers immunoreactive to tyrosine hydroxylase (TH), dopamine-beta-hydroxylase (DBH), phenyletanolamine-N-methyltransferase (PNMT), and serotonin (5-HT). TH- and DBH-immunoreactive fibers were similar and were evenly and densely distributed throughout the tuberomammillary nucleus. Fibers stained with 5-HT antibodies were also present throughout the tuberomammillary nucleus but exhibited the densest labeling in the dendritic layer adjacent to the glia limitans in the ventral subgroup. Innervation by PNMT-immunoreactive axons was sparse. Electron microscopic analysis of TH-, DBH-, and 5-HT-immunoreactive fibers in the tuberomammillary nucleus revealed vesicle-containing terminal boutons, which formed synapses with dendrites of varying size. Synaptic contacts with nerve cell bodies were not found. Retrograde transport of the fluorescent dye Fast Blue injected into the tuberomammillary nucleus, combined with immunofluorescent staining with anti-TH, anti-DBH, anti-PNMT, and anti-5-HT antibodies, showed that monoaminergic input to the tuberomammillary nucleus originated mainly from the adrenergic and noradrenergic cell groups C1-C3 and A1-A2, respectively, and from the serotoninergic cell groups B5-B9 as designated by Dahlström and Fuxe ('65). Few double-labeled neurons were found in the nucleus locus coeruleus and the dopaminergic cell groups of the rostral brain stem. The present findings suggest that the activity of the histamine-producing neurons of the tuberomammillary nucleus is influenced by monoaminergic neurons in the ventrolateral and dorsomedial medulla oblongata and the raphe nuclei of the rostral brainstem.

Afferent Pathways↗
PubMed1989

Distribution of galanin-binding sites in the monkey and human telencephalon: preliminary observations.

Using X-ray film autoradiography the distribution of 125I-galanin binding sites was studied in the forebrain of monkey and man. In the monkey a high density was found in all areas of the neocortex, especially layer 4, and in certain subfields in the hippocampal region. Also in the human brain high activity was seen in neocortex, mainly layer 6 and in hippocampal areas, as well as in amygdala, piriform cortex and hypothalamus. These results suggest that the 29-amino acid peptide galanin may be involved in the regulation of higher cortical functions in primates.

Amygdala↗
PubMed1989

In vivo labelling of pituitary dopamine D-2 receptors in the male rat using [3H]-raclopride.

The substituted benzamide drug [3H]-raclopride (Köhler et al., 1985) was used to label dopamine D-2 receptors within the individual lobes of the pituitary gland as well as in the brain of male rats in vivo. The in vivo [3H]-raclopride binding was found to be saturable, reversible and of high specificity. Between 5-30% of the binding was non-specific at saturating concentrations dependent upon the lobe of the pituitary gland as well as of the brain region (e.g., caudate nucleus and olfactory tubercle) studied. Saturation analyses revealed Bmax-values of 12.9 +/- 1.6 and 2.2 +/- 0.9 pmol.g-1 wet weight in the intermediate and anterior lobes, respectively with respective KD values of 6.5 +/- 4.6 and 7.3 +/- 2.4 nmol.kg-1. Quantitative autoradiographic studies using a single concentration of [3H]-raclopride showed a similar relationship with regard to binding densities in the different lobes, and showed, in addition, that the posterior lobe contained the lowest number of specific [3H]-raclopride binding sites. The binding capacities and affinities of binding were 12.9 +/- 1.7 and 9.2 +/- 2.8 respectively in the caudate nucleus and 6.1 +/- 0.7 and 9.3 +/- 2.7 respectively in the olfactory tubercle. The pharmacological analysis revealed that (S)sulpiride, remoxipride and raclopride were 10 to 125 times more potent than their corresponding isomers [(R)sulpridie, FLA 731(--), and FLB 472, respectively] in blocking the in vivo [3H]raclopride binding in the pituitary gland as well as in brain. The in vivo potency of different D-2 antagonists in preventing the [3H]-raclopride binding in the anterior and intermediate lobes was: spiperone greater than domperidone greater than raclopride greater than (S)sulpiride greater than remoxipride. The D-1 selective antagonist SCH 23390 did not block the in vivo binding of [3H]-raclopride neither in the pituitary lobes nor in the brain. In agreement with these findings the D-2 agonists N,N-propylnorapomorphine and quinpirole (LY 171555) but not the D-1 agonist SKF 38393-A blocked the specific in vivo [3H]-raclopride binding in the pituitary gland as well as in the brain. Comparisons between the relative potencies of different drugs in blocking pituitary and brain D-2 receptors in vivo showed that some drugs, including sulpiride and domperidone, were more potent in the pituitary gland than in the brain, while remoxipride and raclopride were equipotent in the two areas. The D-2 agonists tested appeared to be slightly more potent in the brain than in the pituitary gland.

Animals↗