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Biomedical subjects

H Beckmann

Publications and source records attributed to H Beckmann.

At least 37 records · Page 2Linked to original sources

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

[Prenatal developmental disorders of brain structures in schizophrenic psychoses].

In recent years neuroimaging techniques have revealed various cerebral and structural variances in patients with schizophrenic psychoses. The best established findings are the enlargement of the lateral ventricles and discrete structural deficits in temporobasal structures of the cortex. Neuropathological investigations have detected subcortical as well as cortical variances. Subcortically, the volume of the striatum and the globus pallidus have been found to be enlarged in schizophrenics. Among the cortical deviations, the cytoarchitectonic disturbances of the rostral entorhinal region have been well documented and are especially important. According to neuropathological criteria, they are derived from disturbances of prenatal cell migration within the central nervous system. Due to its close anatomical and functional connection with the hippocampal formation and its being the assembly point of all sensory cortical areas, disturbances of this area could seriously impede the processing and filtering of information within the limbic system. The other hitherto reported structural anomalies, such as the disturbance to the radial order of hippocampal neurons, and the abnormal structures in the frontobasal orbital regions and the rostroventral insula, could be connected to the disturbances of migration within the entorhinal region; the former could be secondary, but still prenatal developments. Well documented are the architectonic changes in the rostral cingulate gyrus which is itself connected with the entorhinal region via the Papez circuit. These findings are supported and supplemented by the results of epidemiological studies which indicate a disturbance of brain development during the second trimenon of the prenatal period. Viral infections (Influenza A2) of mothers during this critical period appear to play an especially important role.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

[Pregnancy infections in mothers of chronic schizophrenic patients. The significance of differential nosology].

In a retrospective study, 16 of 80 mothers of chronic DSM III-R schizophrenics reported having had a serious infectious disease during pregnancy. Eleven of the infections had occurred during the second trimester. Influenza and the common cold with fever were frequent. Ten of 80 female controls also recalled having had an infectious illness during pregnancy. Compared to the controls, mothers of schizophrenics reported more infectious illness during pregnancy, particularly during the fifth month of gestation (p < 0.05). Mothers of familial and of sporadic DSM III-R schizophrenics reported equal frequencies of infections in pregnancy. In contrast, when Leonhard's classification of psychoses was applied, significant differences appeared. Infections during pregnancy were scarcely found in unsystematic schizophrenics (mainly genetically determined according to Leonhard). In systematic schizophrenics (mainly exogenously determined according to Leonhard), a significantly higher frequency of infectious diseases was reported for the second trimester as compred both to controls (p < 0.01) and to unsystematic schizophrenics (p < 0.001). Infections during the fifth month of gestation were exclusively reported in systematic schizophrenics. Thus, in the systematic forms of schizophrenia infections during the second trimester and particularly during the fifth month of gestation seem to play an important role in the etiology and seem to be of causal importance for the various cytoarchitectural abnormalities detected in the central nervous system of schizophrenics.

Adult

3H-spiroperidol binding to peripheral mononuclear cells in schizophrenic and healthy subjects.

3H-spiroperidol binding to peripheral blood mononuclear cells was measured in 28 patients, who fulfilled DSM-III-R-criteria for schizophrenia and 17 healthy subjects. There were no significant differences in characteristic binding parameters (Kd, Bmax) between schizophrenic and healthy subjects. Moreover, there was no relation of binding parameters to any of the subtypes of schizophrenia or to the course of illness according to DSM-III-R-criteria. However, some patients exhibited higher Bmax values without having a unique clinical symptomatology according to known diagnostic criteria. Neuroleptic treatment had no consistent effect on binding parameters intraindividually. Kd and Bmax values were not related to age or gender. In conclusion, despite our previously reported improved methodology, we were not able to corroborate the clinical importance of this "peripheral marker" as a tool for diagnosing schizophrenia or for predicting the response to neuroleptic treatment in our sample of schizophrenic patients.

Adult

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

Imbalance of the Gs and Gi/o function in post-mortem human brain of depressed patients.

The amounts of various G protein subunits in postmortem brain samples from the parietal and temporal cortices were the same in controls and depressive patients as demonstrated by immunoblotting. However, photoaffinity GTP labeling (AAGTP) of Gi/o alpha, but not Gs alpha, was significantly increased in depressives in both cortex regions. Furthermore, the ratio of Gs/Gi/o AAGTP incorporation revealed a significant reduction in depressives in these regions. The present findings suggest that an imbalance of second messengers via G protein function may be involved in the pathophysiology of depression.

Affinity Labels

HAT3.1, a novel Arabidopsis homeodomain protein containing a conserved cysteine-rich region.

Homeodomain proteins have been shown to play a major role in the development of various organisms. A novel Arabidopsis homeodomain protein has been isolated based on its capability to interact with a DNA motif derived from the light-induced cab-E promoter of Nicotiana plumbaginifolia. The homeodomain of this protein, designated HAT3.1, differs substantially from those in other plant homeobox proteins identified so far. Furthermore, HAT3.1 is unique among other Arabidopsis proteins in that it does not contain a leucine zipper motif following the homeodomain. HAT3.1 is further characterized by an N-terminal region that shares substantial sequence similarity with the maize homeodomain protein Zmhox1a. Within this conserved region, the presence of eight regularly spaced cysteine/histidine residues was observed reminiscent of other metal-binding domains. Based on the strong evolutionary conservation of this domain, it is proposed that this region represents a novel protein-motif which is denoted PHD-finger (plant homeodomain-finger). In vitro DNA binding studies demonstrated that HAT3.1 is capable of interacting with any DNA fragment larger than 100 bp. Interestingly, a deletion of the N-terminal PHD-finger domain completely abolished DNA binding, suggesting that this region may play an important functional role in protein-protein or protein-DNA interaction. HAT3.1 mRNA was primarily detected in root tissue, implying a regulatory function of this protein in root development.

Amino Acid Sequence

[Pregnancy and labor complications--their significance in the development of schizophrenic psychoses].

In a retrospective study of 80 chronic DSM III-R schizophrenics and 80 controls, the occurrence of obstetric complications (OCs) into the development of chronic schizophrenias was investigated using Leonhard's distinction in systematic schizophrenia (no obvious familial loading) and unsystematic schizophrenia (mainly genetically determined according to Leonhard). The Lewis & Murray and Fuchs scales were used for evaluation. In both scales, unsystematic schizophrenias did not differ from controls, but those with OCs were significantly (p < 0.01) earlier hospitalized (20.5 years) than those without OCs (25.6 years). Systematic schizophrenics had an increased frequency, severity and total score of OCs compared to controls in the Fuchs scale (p < 0.01). Likewise, in the Lewis & Murray scale systematic schizophrenia showed an increased presence of OCs compared to controls (p < 0.05) and to unsystematic schizophrenia (p < 0.1). Systematic schizophrenias were significantly allocated to maternal infectious diseases during mid-gestation. Patients with maternal infections showed more additional OCs than those without (p < 0.05; Lewis & Murray scale). In systematic schizophrenia, a history of OC was not associated with an early onset of the disease. In the genetic determined schizophrenias prenatal and perinatal disturbances lead to an early onset of the disease, however, in systematic schizophrenias they seem to be of causal importance for the development of the disease.

Adult

[Schizophrenia and birth seasonality--contrary results in relation to genetic risk].

In 1299 DSM III-R schizophrenics a slight excess of winter and spring births was evident when compared to the general population. However, when patients were allocated to different diagnostic subgroups according to the Leonhard classification this remained true only for those forms without obvious genetic loading (cycloid psychoses and systematic schizophrenias). On the contrary those forms with high genetic loading (unsystematic schizophrenias) showed a clearcut decrease of births in these months. This decrease, however, was significantly caused by periodic catatonics and cataphasics, but not by affect-laden paraphrenics. The findings corroborate the hypothesis that exogenous noxious agents, present in a crucial period of brain maturation, may be of etiological significance in schizophrenia with low genetic loading. Further, it was suggested that in some foetuses at high genetic risk for the disorder more abortions, stillbirths, postnatal deaths and early childhood deaths can occur, if additional exogenous noxious agents affect these individuals.

Adult

Differences in P300 amplitudes and topography between cycloid psychosis and schizophrenia in Leonhard's classification.

In a polydiagnostic approach, we investigated the parameters of auditory P300 in a group of 18 remitted schizophrenics and in 18 age- and sex-matched controls. All patients fulfilled the criteria of schizophrenic disorder according to DSM-III-R. Applying Leonhard's classification, patients were to be subdivided into 7 cycloid psychosis and 11 Leonhard's schizophrenics. Patients with cycloid psychosis fulfilled the operational criteria of Brockington et al. We found significantly lower P300 amplitudes in the group of Leonhard's schizophrenics than in controls and in cycloid psychosis, whereas no difference could be shown between patients with cycloid psychosis and controls. Both the maxima and the minima of the P300 field map were dislocated significantly to the right in the group of Leonhard's schizophrenics but not in cycloid psychosis.

Adult

Presentation of human neocortical neurons stained with the carbocyanine dye dil compared to the Golgi silver impregnation technique.

The carbocyanine dye Dil (1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate) not only serves as an excellent neuronal tracer, but also produces staining of neurons similar to the results of the Golgi technique. In one aspect staining with Dil seems superior to the Golgi technique: the axons are well stained and show morphological details of their structure. The dendrites and the spines can also be studied easily so that this technique seems to be a promising alternative of the Golgi technique. The fading of the fluorescence could probably be overcome by photoconversion of the stained neurons.

Brain

[The early childhood form of negativistic catatonia].

In a case report the clinical manifestation of negativistic catatonia with its modified symptomatology by first onset in early childhood is presented. The symptomatology consists of negativism, negativistic excitations with (auto)aggressivity and impulsive behaviour. Development of expressive language is lacking or is arrested. Physical development is retarded. These conditions are seldom recognized but diagnosed as organic brain syndrome or more unspecifically as "pervasive developmental disorder" (DSM III-R, ICD 10).

Adult

Variations of monoamines and their metabolites in the human brain putamen.

The levels of the monoamines dopamine (DA), serotonin (5-HT) and norepinephrine (NE) and the monoaminergic metabolites 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) were measured with HPLC-ECD in 42 samples from human brain putamen. The influence of gender and of age was investigated and correlations between the monoamines were established. The DAergic system shows a significant difference between males and females, with females having lower DA and higher DOPAC levels and a higher DOPAC/DA ratio than males. No gender-related differences of 5-HT and its metabolites were observed, nor of NE. Three different age groups (group 1: 0-9.9 years: group 2: 10-59.9 years; group 3: 60 years and older) were defined according to previous studies on ontogenesis and senescence in human brain. An increase in 5-HT levels, decrease in 5-HIAA levels and a decrease in the 5-HIAA/5-HT ratio were observed after the first decade of life. Changes in the DAergic system were seen in senescence, with decreasing DA levels and an increase in the HVA/DA ratio. DOPAC, HVA and the DOPAC/DA ratio are unaffected. NE is similar in all age groups. The analysis of the relation of the levels of the three monoamines proved a strong correlation between the DAergic and 5-HTergic systems. The nature of this relationship might have an impact on neuro-psychiatric disorders and brain function.

Adolescent

Heterodimerization between light-regulated and ubiquitously expressed Arabidopsis GBF bZIP proteins.

The promoters of a variety of plant genes are characterized by the presence of a G-box (CCACGTGG) or closely related DNA motifs. These genes often exhibit quite diverse expression characteristics and in many cases the G-box sequence has been demonstrated to be essential for expression. The G-box of the Arabidopsis rbcS-1A gene is bound by a protein, GBF, identified in plant nuclear extracts. Here we report the isolation of three Arabidopsis thaliana cDNA clones encoding GBF proteins referred to as GBF1, GBF2 and GBF3. GBF1 and GBF2 mRNA is present in light and dark grown leaves as well as in roots. In contrast, GBF3 mRNA is found mainly in dark grown leaves and in roots. The deduced amino acid sequences of the three cDNAs indicate that each encodes a basic/leucine zipper protein. In addition, all three proteins are characterized by an N-terminal proline-rich domain. Homodimers of the three proteins specifically recognize the G-box motif, with GBF1 and GBF3 binding symmetrically to this palindromic sequence. In contrast, GBF2 binds to the symmetrical G-box sequence in such a way that the juxtaposition of the protein and the DNA element is clearly asymmetric and hence distinct from that observed for the other two proteins. The fact that GBF1, GBF2 and GBF3 possess both distinct DNA binding properties and expression characteristics prompt us to entertain the notion that these proteins may individually mediate distinct subclasses of expression properties assigned to the G-box. Furthermore, we demonstrate that GBF1, GBF2 and GBF3 heterodimerize and these heterodimers also interact with the G-box, suggesting a potential mechanism for generating additional diversity from these GBF proteins.

Amino Acid Sequence

DNA binding site preferences and transcriptional activation properties of the Arabidopsis transcription factor GBF1.

The G-box is a cis-acting element found within the promoters of many plant genes where it mediates expression in response to a variety of different stimuli. This palindromic DNA motif (CCACGTGG) is composed of two identical half sites, the base pairs of which we have numbered -4 to +4 (numbering from 5' to 3'). Both half sites are involved in the binding of the bZIP protein GBF1, a member of the GBF family of Arabidopsis thaliana. Here we demonstrate using the random binding site selection method that GBF1 interacts with, in addition to the palindromic G-box, other DNA motifs that fall into seven distinct groups. All groups share the ACGT core sequence, common to most DNA motifs bound by plant bZIP proteins so far characterized. Our studies demonstrate that a high affinity GBF1 binding site is further defined by the following two parameters: first, all sites contain a G residue at position +3 (as in ACGTG) and secondly, only certain base pair combinations are allowed at positions -4, -3 and +4. Two of the identified groups (TGACGTGG and TGACGTGT) contain the base pairs TG at positions -4 and -3 and hence resemble the binding sites of another class of plant bZIP proteins (TGACGT/C binding proteins). However, GBF1 only interacts with the TGACGT sequence if the two 3' distal nucleotides (positions +3 and +4) are occupied by GG or GT. These data define the differences between a G-box binding protein and TGACGT/C binding proteins. The N-terminal domain of GBF1 is defined by a high proline content. Such regions were also identified in proteins related to GBF1. We demonstrate that this N-terminal proline-rich domain of GBF1, when fused to a heterologous DNA binding domain, stimulates transcription in both plant protoplasts and mammalian cells. These extensive DNA binding studies and the characterization of the GBF1 activation domain will facilitate both the identification of regulatory elements and the in vivo function of GBF1.

3T3 Cells

MRI white matter hyperintensity in neuroleptic malignant syndrome (NMS)--a clue to pathogenesis?

The case of a young female patient with neuroleptic malignant syndrome (NMS) and extended MRI white matter hyperintensity in the left parietal and both occipital lobes is reported. MRI lesions resembled findings in hypertensive encephalopathy, they were not readily compatible with CNS vasculitis. Venous sinus thrombosis could be ruled out. Vascular encephalopathy with transient white matter edema and a small residual left parietal lesion is suggested. Neurochemical implications are discussed with particular reference to a possible involvement of excitatory amino acids in NMS pathogenesis.

Adult