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J Deckert

Publications and source records attributed to J Deckert.

At least 55 records · Page 3Linked to original sources
PubMed1995

Multiple elements and auto-repression regulate Rox1, a repressor of hypoxic genes in Saccharomyces cerevisiae.

The ROX1 gene encodes a heme-induced repressor of hypoxic genes in yeast. Using RNA blot analysis and a ROX1/lacZ fusion construct that included the ROX1 upstream region and only the first codon, we discovered that Rox1 represses its own expression. Gel-retardation experiments indicated that Rox1 was capable of binding to its own upstream region. Overexpression of Rox1 from the inducible GAL1 promoter was found to be inhibitory to cell growth. Also, we found that, as reported previously, Hap1 is partially responsible for heme-induction of ROX1, but, in addition, it also may play a role in ROX1 repression in the absence of heme. There is a second repressor of anaerobic ROX1 expression that requires the general repressor Tup1/Ssn6 for its function.

Aerobiosis↗
PubMed1995

Mutational analysis of Rox1, a DNA-bending repressor of hypoxic genes in Saccharomyces cerevisiae.

Rox1 is a repressor of the hypoxic genes of Saccharomyces cerevisiae. It binds to a specific hypoxic consensus sequence in the upstream region of these genes and represses transcription in conjunction with the general repression complex Tup1-Ssn6. In this study, we demonstrated that the first 100 amino acids comprising the HMG domain of Rox1 were responsible for DNA binding and that when bound, Rox1 bent DNA at an angle of 90 degrees. A mutational analysis resulted in the isolation of seven missense mutations, all located within the HMG domain, that caused loss of DNA binding. The effect of these mutations on the structure of Rox1 was evaluated on the basis of the homology between Rox1 and the human male sex-determining protein SRY, for which a structural model is available. The failure to isolate missense mutations in the carboxy-terminal three-quarters of the protein prompted a deletion analysis of this region. The results suggested that this region was responsible for the repression function of Rox1 and that the repression information was redundant. This hypothesis was confirmed by using a set of fusions between sequences encoding the GAL4 DNA-binding domain and portions of ROX1. Those fusions containing either the entire carboxy-terminal region or either half of it were capable of repression. Repression by selected fusions was demonstrated to be dependent on Ssn6.

Base Sequence↗
PubMed1995

Lilliputian and negative hallucinations in a patient with probable encephalomyelitis disseminata.

A patient who showed Lilliputian hallucinations and negative hallucinations in the course of probable disseminated encephalomyelitis is described. At the age of 14 years the patient experienced a transient, flaccid paresis of the right leg. Eighteen years later she suddenly developed paranoid-hallucinatory symptoms accompanied by atypical visual hallucinations. She did not recover completely and until now she has suffered at least once every year from an episode with psychotic symptoms. During the most recent of these episodes, MRI revealed several disseminated supra- and infratentorial foci in the brain. Two of them, in the left cerebral peduncle and in the left occipital white matter are discussed as the cause of her visual hallucinatory symptoms.

Adult↗
PubMed1994

Memantine inhibits [3H]MK-801 binding to human hippocampal NMDA receptors.

The antispastic agent and N-methyl-D-aspartate (NMDA) receptor antagonist memantine has recently been proposed as a neuroprotective drug for use in patients with dementia syndromes with primarily temporal lobe pathology, e.g. senile dementia of Alzheimer type or dementia in Parkinson's disease. In a quantitative autoradiographic study in human post mortem hippocampus, memantine was able to inhibit binding of the noncompetitive NMDA-antagonist [3H]MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate) with inhibition constants between 3 and 10 microM, being about a factor of 10 more potent than the dissociative anaesthetic and NMDA receptor antagonist (+/-)ketamine. As these inhibition constants are well within the therapeutic concentration range of memantine, antagonism of endogenous glutamate at limbic NMDA receptors may be one molecular mechanism by which memantine is beneficial in dementia syndromes.

Aged↗
PubMed1994

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) inhibit [3H] alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) binding in human hippocampus.

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) have been investigated with regard to their potency to inhibit [3H] alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA) binding in human hippocampus in a quantitative autoradiographic study. With dissociation constants (KD) of [3H]AMPA binding and inhibition concentrations (IC50) of L-BOAA, 6-OH-DOPA and L-glutamate obtained from saturation and displacement experiments inhibition constants (Ki) for the inhibition of [3H]AMPA binding in individual hippocampal subregions could be calculated. They were between 5.2 +/- 2.9 and 35.1 +/- 39.9 microM for L-BOAA and 39.1 +/- 26.8 and 59.4 +/- 44.1 microM for 6-OH-DOPA. L-BOAA was equally potent as the endogenous agonist L-glutamate with Ki's between 13.1 +/- 3.9 and 21.4 +/- 12.1 microM (n = 4, mean +/- S.D.). Limbic system symptoms like cognitive deficits, mood disturbances and vivid dreams observed in patients with the motor neuron disease neurolathyrism may thus well be mediated by agonistic action of L-BOAA at AMPA glutamate receptors in hippocampus.

Aged↗
PubMed1994

(3H)dipyridamole and (3H)nitrobenzylthioinosine binding sites at the human parietal cortex and erythrocyte adenosine transporter: a comparison.

We compared the binding sites of the adenosine transport inhibitors (3H)dipyridamole (DPR) and (3H)nitrobenzylthioinosine (NBI) in human parietal cortex and erythrocytes. In comparison with guinea pig (3H)DPR marked only slightly more binding sites than (3H)NBI with a Bmax of 1080 +/- 29 and 780 +/- 7 fmol/mg protein respectively in parietal cortex and 24288 +/- 2725 and 20875 +/- 1905 fmol/mg protein respectively in erythrocytes. NBI displaced (3H)DPR binding completely from its binding sites at about KD/2 concentrations in parietal cortex as well as erythrocytes with inhibition constants comparable to its dissociation constants. Lineweaver-Burke analysis in erythrocytes indicated a competitive inhibition of (3H)DPR binding by NBI. Pharmacological characterization of (3H)DPR binding sites in human erythrocytes is consistent with their localization on adenosine transporters. These findings provide evidence that as opposed to guinea pig (3H)DPR and (3H)NBI largely label binding sites to the same adenosine transporter in human erythrocytes and parietal cortex.

Adenosine↗
PubMed1994

Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study.

Neurotoxic substances are discussed to cause neurodegeneration by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4, 6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease.

Amino Acids, Diamino↗
PubMed1994

Adenosine--an endogenous neuroprotective metabolite and neuromodulator.

Adenosine is now widely accepted as the major inhibitory neuromodulator in the central nervous system besides GABA. It has been suggested to be an endogenous neuroprotective metabolite. In situations of metabolic stress, e.g. ischemia adenosine decreases energy demand and increases energy supply. Of particular relevance in this context is its modulation of glutamate release. A shift of this adenosine-glutamate balance in favor of adenosine helps to restore function at the cellular, organ and organism level. Adenosine A1 receptor agonists and metabolic inhibitors, e.g. of transport, deaminase and xanthine oxidase have been demonstrated to be effective in different animal models of ischemia. Nimodipine, a L-type channel calcium antagonist currently in clinical trials for stroke and dementia syndromes, has now been shown to be a potent adenosine transport inhibitor in clinically relevant concentrations. Increase of adenosinergic neuromodulation may well be one of several future therapeutic strategies in neuroprotection.

Adenosine↗
PubMed1993

Nimodipine inhibits [3H]nitrobenzylthioinosine binding to the adenosine transporter in human brain.

The inhibition of [3H]nitrobenzylthioinosine ([3H]NBI) binding to human parietal cortex membranes by adenosine transport inhibitors, adenosine receptor agonists and antagonists and dihydropyridines was investigated. While the adenosine transport inhibitors inhibited [3H]NBI binding with Ki values in the low nanomolar range and the adenosine A1 receptor agonist, cyclopentyladenosine, with a Ki in the low micromolar range, no IC50 values could be obtained for the adenosine receptor antagonists at concentrations up to 100,000 nM. Among the dihydropyridines (+)-nimodipine was the most potent with a Ki of 201 +/- 55 nM. Inhibition of adenosine transport thus may contribute to the clinical effects of nimodipine in the central nervous system.

Dihydropyridines↗
PubMed1993

Adenosine A1 receptors in human hippocampus: inhibition of [3H]8-cyclopentyl-1,3-dipropylxanthine binding by antagonist drugs.

Adenosine A1 receptors were visualized in human hippocampus using [3H]8-cyclopentyl-1,3-dipropylxanthine (DPCPX) as a radioactive ligand probe. The receptor antagonists caffeine, the xanthine derivative KFM 19 and the carbamazepine analogue oxcarbazepine displaced [3H]DPCPX binding homogeneously without any marked difference between the individual layers in the investigated hippocampal subregions (n = 4). Ki's in the individual layers were in a range between 8.5 +/- 6.5 microM and 18.9 +/- 16.0 microM for caffeine and 11.5 +/- 2.8 nM and 18.1 +/- 14.1 nM for KFM 19. Ki's could not be calculated for oxcarbazepine as the IC50's were greater than 100 microM with estimated IC25's varying between 51.2 +/- 53.3 microM and 179.9 +/- 89.9 microM. Antagonism of endogenous adenosine at A1 receptors may thus explain part of the clinical effects of caffeine in humans and possibly exclusively the behavioral effects of KFM 19 in non-human primates.

Aged↗
PubMed1992

Potential use of DPCPX as probe for in vivo localization of brain A1 adenosine receptors.

The suitability of (3H)DPCPX (8-cyclopentyl-1,3-dipropylxanthine), a xanthine derivative, as an vivo probe for labelling adenosine A1 receptors was studied in rats. [3H]DPCPX (nM) penetrated largely into the brain (0.8% of the injected dose per gram of brain tissue 5 min after injection). Brain concentrations stayed at a plateau level from 5 to 15 min after the injection. The distribution in the different brain regions was heterogeneous with the highest amount of [3H]DPCPX in cerebellum and hippocampus and the lowest concentrations in hypothalamus and brain stem. Displacement (45-70% of total radioactivity) was obtained by the injection of 250 nM of cold DPCPX or cyclopentylxanthine, an analog of DPCPX. The ex vivo autoradiographic distribution of [3H]DPCPX was similar to the in vitro autoradiographic distribution of tritiated A1 adenosine receptor ligand as [3H]CHA. These results suggest the potential use of DPCPX for further in vivo investigation of A1 adenosine receptors with techniques such as positron emission tomography.

Animals↗
PubMed1992

Organic schizophrenic syndrome associated with symmetrical basal ganglia sclerosis and XO/XY-mosaic.

Psychopathological alterations associated with symmetrical basal ganglia sclerosis have been well characterized. A preponderance of a so-called organic affective syndrome has been reported (König 1989), but schizophrenic syndromes have also been described, in particular in young patients (Cummings et al 1983). Symmetrical basal ganglia sclerosis may be secondary to ischemia, hypoxia, trauma, intoxications, inflammations, or hyporesp. pseudohypoparathyroidism. Among idiopathic forms sporadic as well as familial ones with dominant and recessive inheritance have been observed (Billard et al 1989).

Adult↗
PubMed1992

[Status of amine hypotheses in depressive disorders].

The biochemical effects of drugs modulating mood are the basis for still relevant hypotheses relating depressive disorders to dysfunctions of noradrenergic, serotonergic and/or cholinergic neurotransmission. The time course as well as the dose-effect-relationships point to the relevance for mood elevation of secondary adaptive processes rather than the direct actions of antidepressants. Direct evidence of dysfunctions sufficiently explaining the actual illness of the single individual has not been obtained at the level of transmitters, metabolites and receptors. Deficits of serotonergic transmission seem to be related to a personality dimension of poor impulse control closer than to nosological categories. This dimensional concept might also be valid for the relationships between cholinergic sensitivity and stress tolerance. Depression itself is possibly due to imbalances of multiple neuronal systems.

Acetylcholine↗
PubMed1991

Post- and presynaptic lesions in the CA1 region of hippocampus: effect on [3H]forskolin and [3H]phorboldibutyrate ester binding.

The effect of transient cerebral ischemia and intraventricular injection of kainic acid on adenylate cyclase and protein kinase C as labeled by [3H]forskolin ([3H]FOR) and [3H]phorboldibutyrate ester ([3H]PDBU) in several rat brain microregions was investigated in a quantitative autoradiographic study. Four days after transient four vessel occlusion a 80% loss of [3H]FOR and a 35% loss of [3H]PDBU binding could be measured in the CA1 stratum radiatum of operated Wistar rats as compared to control rats. Four days after intraventricular injection of kainic acid only a marginal loss of [3H]FOR and a 30% increase of [3H]PDBU binding was seen in the CA1 stratum radiatum while in the CA3 stratum lucidum and radiatum respectively a 30% loss of [3H]FOR and no significant change in [3H]PDBU binding was observed. As transient cerebral ischemia and intraventricular kainic acid injection are depleting the hippocampal CA1 region of CA1 pyramidal cells and axons of CA3 pyramidal cells respectively in rat brain, these findings strongly suggest that both adenylate cyclase and protein kinase C are localized in CA1 pyramidal cells of rat hippocampus.

Adenylyl Cyclases↗
PubMed1990

Late ontogenetic development of adenosine A1 receptor coupling to associated G-proteins in guinea pig cerebellum but not forebrain.

The ontogenetic profile of [3H]forskolin and [3H]cyclohexyladenosine [( 3H]CHA) binding sites in guinea pig forebrain and cerebellum was investigated. G-protein interactions of these binding sites were also examined by analyzing 5'-guanylylimidodiphosphate (Gpp(NH)p) interactions with [3H]CHA and [3H]forskolin binding. In forebrain, similar binding characteristics of [3H]CHA and [3H]forskolin binding are observed between the developmental stages E36 (the earliest time point studied) through to adult (P28, the latest time point studied), although transient increased binding of both ligands is observed just prior to birth. Scatchard analysis of binding isotherms reveal that this transient rise just prior to birth is due to an increase in the number of binding sites (Bmax) with little or no change in receptor affinity (Kd). In contrast, in cerebellum both [3H]CHA and [3H]forskolin binding remains at a relatively low level until just prior to birth when a dramatic increase of binding of both ligands is observed which continues to increase up to P28. Scatchard analysis of binding isotherms reveal that such changes in binding of both ligands are largely due to increases in Bmax and not Kd, although Scatchard analysis of [3H]CHA binding to cerebellar E51 membranes reveals an absence of higher affinity [3H]CHA binding sites. Gpp(NH)p did not affect [3H]forskolin binding. Gpp (NH)p displacement profiles of [3H]CHA binding reveal a maximum (adult) inhibition of [3H]CHA binding (approximately 80% displacement) at all time points (E36 through P28) in forebrain membranes, but not in cerebellar membranes. In cerebellum, displacement of [3H]CHA binding by Gpp(NH)p is much greater after birth than before birth.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine↗