Season-of-birth effect reveals the existence of etiologically different groups of schizophrenia.
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Cyclothymic Disorder↗
Biomedical subjects
H Beckmann
Publications and source records attributed to H Beckmann.
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↗
Temporal lobe cytoarchitectural neuropathology in schizophrenia.
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Female↗
TGA1 and G-box binding factors: two distinct classes of Arabidopsis leucine zipper proteins compete for the G-box-like element TGACGTGG.
Regulatory elements containing the sequence ACGT are found in several plant promoters and are recognized by various basic/leucine zipper (bZIP) proteins. The Arabidopsis G-box binding factor 1 (GBF1), initially identified by its ability to bind to the palindromic G-box (CCACGTGG), also interacts with the TGACGT motif if this hexamer sequence is followed by either the dinucleotide GG--as found in the Hex motif of the wheat histone 3 promoter--or GT. Here we describe the isolation of an Arabidopsis bZIP protein, denoted TGA1, that also recognizes ACGT-containing sequences. However, TGA1 differs from members of the GBF family in the spectrum of base pair permutations flanking the ACGT sequence that are required for DNA binding. TGA1 primarily requires a TGACG motif and preferentially binds to those pentamers that are followed by a T residue. We show that although both TGA1 and GBF1 bind to the Hex motif (TGACGTGG), this binding can be distinguished on the basis of their specific DNA-protein contacts. Furthermore, TGA1 also differs from members of the GBF family in that it apparently does not form heterodimers with any member of this family.
Amino Acid Sequence↗
The influence of neuroleptics on specific syndromes and symptoms in schizophrenics with unfavourable long-term course. A 5-year follow-up study of 50 chronic schizophrenics.
Fifty chronic schizophrenics with severe residual psychopathology were followed up over a 5-year period. All of them had continuously received neuroleptics for many years before and throughout the period of investigation. In 60% (n = 30) of the patients positive symptoms which were unchanged in quality and severity were present throughout the period of investigation. In 28% (n = 14) of the patients marked positive symptoms persisted from the very beginning up to 1990 (in every case more than 20 years). Applying Leonhard's classification it was obvious that syndromes are roughly unchanged with respect to the preneuroleptic era. In these patients neuroleptics seemed to have only unspecific suppressing effects on affectivity. It is supposed that in schizophrenia which leads to severe residual psychopathology, Leonhard's classification is superior to the positive-negative distinction and is a promising concept for future research in etiology and therapy.
Adult↗
Deficit of birthrates in winter and spring months in distinct subgroups of mainly genetically determined schizophrenia.
The birthrates of 507 schizophrenic patients with high familial loading were compared to the general population. The patient group showed a clearcut decrease in births within a defined winter and spring period. In particular, this was obvious if Leonhard's classification of schizophrenia was applied. The hypothesis is proposed that, in some fetuses at high genetic risk for schizophrenia, an exaggerated level of abortions or stillbirths occurs if additional environmental noxious agents are present in a crucial period of brain maturation. Pertinent evidence in support of this is found in literature.
Adult↗
Sex differences and distinct subgroups in schizophrenia. A study of 54 chronic hospitalized schizophrenics.
Sex differences with regard to age at first hospitalization and residual symptomatology were investigated in 54 long-term hospitalized chronic schizophrenics. Patients fulfilled diagnostic criteria of DSM-III, Kraepelin's dementia praecox and Leonhard's group of schizophrenias as well. The severe residual psychopathology necessitated continuous hospitalization in all the patients. The 27 women and 27 men neither differed in duration of illness or period of hospitalization nor in their social environment. We found that women were older than men at their first hospitalization and exhibited more marked positive symptomatology during the course and in the residual state than men. However, regardless of the residual symptomatology, men generally received more neuroleptics. A classification of the schizophrenic patients by means of the Leonhard criteria revealed that unsystematic schizophrenics (affect-laden paraphrenia, periodic catatonia, cataphasia) of both sexes were significantly (p less than 0.001) more often married at the time of first hospitalization than were systematic schizophrenics. Further, there was an overwhelming preponderance of women among the group of affect-laden paraphrenia and, conversely, of men in the group of periodic catatonia. Presuming different etiology in affect-laden paraphrenia and periodic catatonia, our findings suggest a significantly varied frequency in the rate in which women and men are afflicted by heterogeneous subgroups of schizophrenia.
Chronic Disease↗
[Electroconvulsive therapy in treatment of acute life threatening catatonia in toxic epidermal necrolysis (Lyell syndrome)].
Toxic epidermal necrolysis (Lyell syndrome) developed in a 43-year woman treated with carbamazepine, perazine, and sulpiride for recurrent manic bipolar disorder. Five days after withdrawal of all psychotropic medication her psychiatric illness was exacerbated and a syndrome of lethal catatonia developed which was promptly treated with unilateral electroconvulsive therapy (ECT). Rapid remission of lethal catatonia after the first ECT treatment and of her affective disorder within days was achieved. According to clinical observations of the preneuroleptic era, early improvement of lethal catatonia following ECT may have been supported by concurrent high dose corticosteroid therapy for toxic epidermal necrolysis.
Adult↗
Disturbed glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressives pretreated with metyrapone.
We studied glucocorticoid receptor autoregulation and corticotropin response to dexamethasone in depressed patients and controls, attempting to control for the confounding effect of endogenous glucocorticoids. After depletion of endogenous cortisol, depressed patients showed an attenuated suppressibility of corticotropin by dexamethasone in the face of unchanged dexamethasone plasma levels. Beta-endorphin levels were strongly correlated with adrenocorticotropic hormone (ACTH) concentrations. Although metyrapone administration resulted in a marked rise of glucocorticoid receptor sites per cell in controls, this effect was not present in depressives. These data support the hypothesis of a decreased glucocorticoid receptor plasticity and a partial steroid resistance in depression.
Adolescent↗
Hippocampal neuron number in schizophrenia. A stereological study.
Neuropathologic and neuroradiologic studies have reported hippocampal abnormalities in schizophrenics. We estimated the total number of neurons in the hippocampus of schizophrenics and controls to elucidate the neuronal basis of such changes. Thirteen brains of schizophrenics and 13 control brains closely matched for sex and age were studied. A new stereological method was applied to serial coronal sections through the whole hippocampus. Total hippocampal volume was reduced in the schizophrenic sample, more pronounced on the left side, but mean differences were not significant. The volumes of the pyramidal cell layer in the four subdivisions subiculum and cornu Ammonis sectors CA 1, CA 2/3, and CA 4 were almost identical in both groups. Schizophrenics did not differ from controls with regard to nerve cell density in any of the four subdivisions. The estimates of the total number of neurons in the hippocampal subdivisions were not different between schizophrenics and controls. The data do not support the hypothesis that hippocampal abnormalities are caused by neuronal cell loss. However, they are consistent with the suggestion that white matter changes in the hippocampus may play a role in the pathogenesis of schizophrenia.
Adult↗
In vivo and in vitro effects of glucocorticoids on lymphocyte proliferation in depression.
Twelve severely depressed patients and 13 healthy controls were studied under baseline, metyrapone and metyrapone plus dexamethasone pretreated conditions. Lymphocyte proliferation data were obtained by concanavalin A, phytohaemagglutinin and pokeweed mitogen (PWM) stimulation. There was a decrease in PWM-induced B-cell proliferation and an increase in inhibition of spontaneous leucocyte proliferation by dexamethasone added in vitro following metyrapone administration in vivo, in healthy controls, which was not present in the depressed patients. These data support the concept of a decreased functional plasticity of the glucocorticoid receptor in depression also at the cellular level.
Adolescent↗
A double-blind comparative multicentre study of controlled-release remoxipride, immediate-release remoxipride and haloperidol in schizophrenia.
A double-blind multicentre study comparing the efficacy and safety of remoxipride in controlled-release formulation (REM-CR), given once a day, and immediate-release formulation (REM-IR) and haloperidol, given twice daily, was conducted in patients with schizophrenic illness. In total, 150 inpatients were randomized: 49, 51 and 50 in the REM-CR, REM-IR, and haloperidol groups, respectively. The mean daily dose of REM-CR during the last week of treatment was 361 mg, that of REM-IR 332 mg. In the haloperidol group the corresponding dose was 12.5mg per day. The study treatment period was four weeks. The median BPRS total score was 37.5 in the REM-CR group at start of treatment, and 14.5 at last rating (n = 38). For the REM-IR group and the haloperidol group the corresponding figures were 36.0 and 38.0 at start of treatment and 18.0 (n = 43) and 16.5 (n = 40) at last rating. No statistically significant differences were found between the treatments. Therapy-emergent extrapyramidal symptoms (Simpson & Angus rating scale) were significantly (p less than 0.05) more frequent and more severe during haloperidol than during REM-CR and REM-IR treatment, despite significantly higher concurrent use of anticholinergic drugs in the haloperidol group.--REM-CR was comparable in efficacy and tolerability to REM-IR. The tolerability profile favoured both remoxipride formulations over haloperidol. Evaluation of the clinical chemistry, haematology, and cardiovascular data showed no clinically significant deleterious effects on any organ system for either drug.
Adolescent↗
Modulation of the IgH enhancer's cell type specificity through a genetic switch.
Using defined regions of the immunoglobulin heavy-chain enhancer linked to minimal promoters and cDNAs that encode the two helix-loop-helix transcription factors ITF-1 and TFE3, we demonstrate that activity of an otherwise repressed enhancer can be stimulated in nonlymphoid cells. Repression in non-B cells is mediated by the microE5 motif. Derepression occurs at two levels. First, overexpression of ITF-1, and E12/E47-related protein that binds the microE5 motif, leads to transcriptional activation itself. Second, binding of ITF-1 physically displaces a repressor that normally blocks the stimulatory activity of TFE3, which binds the neighboring microE3 motif. TFE3 can only stimulate enhancer activity in the presence of ITF-1 or in the absence of a microE5 motif. Hence, one component of the enhancer's cell type specificity can be artificially modulated through a "genetic switch" in which activity is dictated by the relative levels of ITF-1 and a competing repressor.
Base Sequence↗
[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↗
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↗