PubMed Health⌕ Search

Biomedical subjects

H Beckmann

Publications and source records attributed to H Beckmann.

At least 37 records · Page 2Linked to original sources
PubMed1991

The leucine zipper of TFE3 dictates helix-loop-helix dimerization specificity.

TFE3 is a DNA-binding protein that activates transcription through the muE3 site of the immunoglobulin heavy-chain enhancer. Its amino acid sequence reveals two putative protein dimerization motifs: a helix-loop-helix (HLH) and an adjacent leucine zipper. We show here that both of these motifs are necessary for TFE3 to homodimerize and to bind DNA in vitro. Using a dominant negative TFE3 mutant, we also demonstrate that both the HLH and the leucine zipper motifs are necessary and sufficient for protein-protein interactions in vivo. TFE3 is unable to form stable heterodimers with a variety of other HLH proteins, including USF, a protein that is structurally similar to TFE3 and binds a common DNA sequence. The analysis of "zipper swap" proteins in which the TFE3 HLH was fused to the leucine zipper region of USF indicates that dimerization specificity is mediated entirely by the identity of the leucine zipper and its position relative to the HLH. Hence, in this "b-HLH-zip" class of proteins, the leucine zipper functions in concert with the HLH both to stabilize protein-protein interactions and to establish dimerization specificity.

Amino Acid Sequence↗
PubMed1991

[Syndrome and symptom development in long-term follow-up of schizophrenia].

In a five year follow-up study of 57 hospitalized chronic schizophrenics we investigated the development of symptoms and syndromes, taking into account different nosological concepts. We could demonstrate that after a careful methodological training Leonhard's differentiated classification of schizophrenia is highly reliable. Analyses of the long-term course of individual syndromes showed that a dichotomy into positive and negative symptoms does not provide a reliable prognosis. Within the Leonhard classification, however, a remarkable homogeneity was evident with regard to course and outcome of various schizophrenic subtypes. Investigating the biography of the kinships we found further indication of nosologic heterogeneity, particularly between unsystematic (high hereditary loading) and systematic schizophrenias (almost no hereditary loading). However, the strategy of a simple dichotomy into familial/sporadic cases appears to have too many methodological shortcomings. Further, the study showed that, in this cohort, neuroleptic long-term treatment did not decisively influence the development of residual states, with or without residual marked positive symptoms. It is suggested that the Leonhard classification is a promising concept for further psychopathological as well as biological investigations in psychiatry.

Aged↗
PubMed1990

Limbic structures and lateral ventricle in schizophrenia. A quantitative postmortem study.

Volume reduction of limbic structures in the medial temporal lobe of schizophrenics has been described in postmortem analyses of two brain collections. A total of 30 hemispheres of schizophrenics and 30 hemispheres of controls taken from a new collection of brains and closely matched for sex and age were examined. We applied computer-assisted stereologic methods to serial coronal sections of complete hemispheres. Volumetric measurement of amygdala, hippocampal formation, and lateral ventricle was performed. We found no significant volume reduction of amygdala and hippocampal formation in schizophrenics. Bilateral enlargement of the lateral ventricle was found in the schizophrenic group, but mean differences were not significant, and no correlation with limbic structure volumes was found. We postulate methodologic issues of postmortem volumetric measurements and matching of samples as possible reasons for the failure to replicate previous findings.

Adult↗
PubMed1990

Clinical, biochemical and psychometric findings with the new MAO-A-inhibitors moclobemide and brofaromine in patients with major depressive disorder.

N = 53 inpatients with major depressive disorder have been treated with the reversible, selective MAO-A-inhibitors moclobemide (double-blind versus maprotiline) and brofaromine (open study), respectively. Clinically, significant improvement of depression and an activating profile of action could be observed, typical side effects were sleep disturbances, agitation and weight loss. The neurobiochemical data showed an increase of noradrenaline plasma concentrations under treatment with moclobemide. Visual reaction times improved with antidepressant treatment. MAO-A inhibitors proved to be effective antidepressants in the treatment of hospitalized patients with predominantly endogenous depressions.

Benzamides↗
PubMed1990

Reflection of changes in membrane constituents in various regions of Alzheimer brains to differential scanning thermograms.

To test whether changes in basic biochemical membrane constituents were reflected in membrane fluidity measurements, protein, total lipids, triglycerides, lecithin, cholesterol and alkaline phosphatase were determined in frontal cortex, hippocampus, putamen and nucleus basalis Meynert (NbM) of DAT brains and controls and compared to differential scanning thermograms. Biochemical changes were most pronounced in the hippocampus, while thermostability was altered in the NbM and the frontal cortex. The results indicate that changes in protein content, but not in lipid composition were reflected in alterations of thermostability of the brain regions examined.

Aged↗
PubMed1990

MRI findings in medial temporal lobe structures in schizophrenia.

In an MRI volumetric study of 10 young male schizophrenics (DSM-III-R 295.9x) a temporal lobe segment, corresponding hippocampal formation and parahippocampal gyrus were found smaller as compared with healthy controls while temporal horn was enlarged. Temporal lobe segment and parahippocampal gyrus were larger on the right in patients and controls, reversed asymmetry was found for the hippocampus.

Adult↗
PubMed1990

[The serotonin hypothesis of depression].

Current theoretical and experimental developments in serotonin research extend from the differentiated description of central cytoarchitectonic structures over the identification and characterization of multiple receptor subtypes by pharmacological and molecular biological methods to the elucidation of neurobiochemical and physiological mechanisms of interneuronal communication and postreceptor signal transduction. These advances parallel the modification and optimization of various strategies for researching the relevance of central serotonergic neurotransmission in the aetiopathogenesis of affective disorders. Strategies such as the paradigm of selective pharmacological provocation contribute significantly to the formulation of complex hypotheses on the physiological regulation of receptor sensitivity, on receptor function in depression and on the processes of therapeutically induced neuroadaptation. In addition it appears that the generation of hypotheses receives further input from fundamental advances at the level of molecular pharmacology and biology. Reviewing and integrating our current knowledge to define the present state of the art facilitates the assessment of the position of serotoninergic function in the pathophysiology of affective disorder and in the mechanisms of action of various therapeutic measures.

Brain↗
PubMed1990

TFE3: a helix-loop-helix protein that activates transcription through the immunoglobulin enhancer muE3 motif.

The muE3 motif within the immunoglobulin heavy-chain enhancer is required for full enhancer activity and is known to bind one, or perhaps a family, of related ubiquitous nuclear proteins. Here, we present the isolation of a cDNA that encodes an apparently novel microE3-binding protein designated TFE3. The major open reading frame of the cDNA predicts a protein of 59 kD, with a leucine zipper situated adjacent to an myc-related motif that has been proposed to assume a helix-loop-helix structure. Both of these motifs have been shown (for other proteins) to facilitate protein-protein interactions and DNA binding. Expression of the cDNA in 3T3 cells stimulates transcription from an artificial promoter consisting of four muE3 sites linked to a TATA box and also augments transcription of a reporter gene when it is linked to multiple copies of a particular heavy-chain enhancer subfragment but not when it is linked to the intact enhancer. Using GAL4 fusion proteins, we mapped a strong transcription activation domain within TFE3 that is distinct from the leucine zipper and helix-loop-helix motifs and includes a potential negative amphipathic helix. Like the other muE3-binding proteins detected in nuclear extracts, in vitro-synthesized TFE3 also binds to the USF/MLTF site found in the adenovirus major late promoter.

Amino Acid Sequence↗
PubMed1990

Guidelines for the dosage of antipsychotic drugs.

When commonly recommended guidelines for the dosage of neuroleptic drugs are critically reviewed, unanswered questions outnumber accepted rules. The relationship between dose and therapeutic efficacy remains far from clear, and despite lack of data there has been a trend in recent years to escalate dosage. Average clinical antipsychotic potency correlates closely with the affinity of the drug for dopamine (D2) receptors. Correlations of blood levels of neuroleptics with clinical efficacy are inconsistent. Assessments of immediate and follow-up treatment indicate that moderate doses are adequate for most psychotic patients and fail to support the use of high doses (more than the approximate equivalent of 300-600 mg chlorpromazine daily). Occasionally however, patients, perhaps because of idiosyncratic pharmacokinetics, require higher doses and do not conform to the statistical data for outcome. More precise results for determining the optimum dose of antipsychotic compounds in schizophrenics in the future, may be available from positron emission tomographic (PET) techniques.

Antipsychotic Agents↗
PubMed1990

A double-blind multicentre study comparing remoxipride, two and three times daily, with haloperidol in schizophrenia.

A double-blind multicentre study comparing the efficacy and safety of remoxipride in relation to haloperidol was conducted in 160 inpatients with schizophrenic illness diagnosed according to DSM-III. The study period was 4 weeks. The mean daily dose of remoxipride (whether given twice or three times daily) during the last week of treatment was 395 mg; the corresponding dose of haloperidol was 17 mg per day. No significant difference in therapeutic efficacy was found; Brief Psychiatric Rating Scale (BPRS) median total scores dropped from 41 to 20 (remoxipride twice daily, n = 51), 43 to 20 (remoxipride three times daily, n = 44) 40 to 19 (haloperidol three times daily, n = 48) at last valid rating. According to Clinical Global Impression (CGI) 68% in the remoxipride twice daily, 58% in the three times daily and 60% in the haloperidol group were very much or much improved. Treatment-emergent extrapyramidal checklist symptoms (hypokinesia, rigidity and tremor) were statistically significantly more frequent and more severe during haloperidol than during remoxipride treatment despite a statistically significantly higher concurrent use of anticholinergic drugs in the haloperidol group. Haloperidol treated patients reported more tiredness and drowsiness than remoxipride treated patients. Also, haloperidol treated patients had a significantly higher frequency of extrapyramidal symptoms on 8 out of 10 items of the Simpson and Angus scale.

Acute Disease↗
PubMed1990

Prognostic validity of the cycloid psychoses. A prospective follow-up study.

In a prospective 4-year follow-up study, 26 out of 31 patients initially diagnosed as cycloid psychoses were investigated (anxiety-happiness psychosis n = 15; confusion psychosis n = 8; motility psychosis n = 3). Patients were independently interviewed by two clinical researchers. 61.5% showed one or several 'first-rank symptoms' according to Schneider. In addition, the SADS-LA was applied for RDC and DSM-IIIR diagnoses. According to these classification systems most of the patients were diagnosed as schizophrenic or schizoaffective. Personal interview as well as application of the Strauss-Carpenter Outcome Scale indicated a highly favorable clinical outcome, i.e. lack of affective or behavioral defective states in literally all patients of the study. These results justify the distinction of the cycloid psychoses as a nosological entity in general and--less convincingly--of the three subtypes of cycloid psychoses.

Adult↗
PubMed1990

Puerperal and cycloid psychoses. Results of a retrospective study.

Puerperal psychoses are traditionally considered to be nosologically unspecific. They are defined exclusively by their occurrence close to delivery. Attempts to further diagnostically subdivide puerperal psychoses have been prevented to date by the influence of Kraepelin's dichotomy. New possibilities of nosological differentiation arose out of Kasanin's (1933) description of schizoaffective psychoses and out of Leonhard's differentiated nosology (1986). The objective of the present, retrospective study was to apply Leonhard's nosology to 42 postpartal psychoses. Five diagnostic groups could be identified: 6 cases of manic-depressive disorder, 7 cases of pure depression, 8 cases of pure melancholia, 2 cases of unsystematic schizophrenia, and 19 cases of cycloid psychoses. For this reason we consider that the concept of the cycloid psychoses is appropriate for the characterization of a large proportion of childbed psychoses.

Adult↗
PubMed1979

[Meproscillarin in patients with renal failure and concomitant heart failure (author's transl)].

Meproscillarin is a glycoside with a high bioavailability (about 70%) and an elimination independent of the renal function. It was to be investigated whether a good cardiac effectiveness can be demonstrated during oral long-term application of meproscillarin to patients with renal failure. 29 patients with renal failure of varying degree and concomitant heart failure were daily given an oral dose of 0.75 mg of meproscillarin over 14 days. The effectiveness of the glycoside was measured as change of the electromechanical systole (QS2c) and the quotient of the diameter of heart and thorax (C/T) from the 1st--15th day. The plasma levels of the glycoside were determined on the 1st, 8th, and 15th day. There was a significant shortening of QS2c (by mean = 27 ms, P less than 0.005) and a marked decrease in the size of the heart (P less than 0.0025); heart rate and PQ-interval were only insignificantly influenced. Plasma levels of 0.95 ng/ml were found after 8 days of treatment compared to 1.25 ng/ml after 15 days. As the pharmacokinetics of the glycoside is practically not influenced by the renal function, meproscillarin represents an alternative in the treatment of patients with heart failure and impaired renal function.

Adult↗
PubMed1979

DL-phenylalanine versus imipramine: a double-blind controlled study.

In a double-blind study, DL-phenylalanine (150--200 mg/24 h) or imipramine (150--200 mg/24 h) was administered to 40 depressed patients (20 patients in each group) for 30 days. Diagnoses were established according to the International Classification of Disease (ICD). The AMP system, the Hamilton Depression Scale and the Bf-S self rating questionnaire (von Zerssen et al., 1974) were used to document psychopathological, neurologic, and somatic changes. Twenty-seven patients (14 on imipramine, 13 on phenylalanine) completed the 30-day trial. No statistical difference could be found between these two drug treatment groups (Student's t-test) using the Hamilton Depression Scale and the Bf-S self rating questionnaire. Ratings for anxiety were significantly lower in the imipramine group on days 10 and 20, but not on day 30; in addition, sleep disturbances were more influenced by imipramine on days 1, 5, and 10, but not on days 20 and 30. Separate analysis of psychopathological syndromes as somatic depressive syndrome and retarded depressive syndrome did not show a group difference (0.05 level of significance using a two-way analysis of variance). It is concluded that DL-phenylalanine might have substantial antidepresant properties. However, certain methodological considerations still warrant a careful interpretation.

Adult↗
PubMed1979

Effect of moderate exercise on urinary MHPG in depressed patients.

This study attempted to clarify sources of artefact in biochemical studies with affective disorders in which 3-methoxy-4-hydroxy phenylglycol (MHPG) is used as a measurement of change in central nervous system norepinephrine (NE) turnover. Substantial increases in urinary MHPG excretion occurred in ten of the 11 patients when they increased their level of physical activity (0.5 +/- .14 mg/12 hrs versus 1.54 +/- .49 mg/12 hrs). Increases were also observed in NE (19.2 +/- 5.1 microgram/12 hrs versus 25.2 +/- 3.7 microgram/12 hrs). In four patients in whom cerebrospinal fluid MHPG levels were obtained a consistent increase of MHPG levels was observed during the activity period. Elevation of these metabolites were not correlated with changes in depression as reflected by psychiatric observation and rating scales. These data reveal a considerable amount of lability in urinary and CSF MHPG levels in the face of an unchanging affective state. They ask for careful controls for activity and stress in psychiatric patients when urinary MHPG is used as an index of central NE turnover.

Depression↗