Neuropsychological profiles of FMR-1 premutation and full-mutation carrier females

The present French-German investigation of fragile-X syndrome (fra-X) was undertaken to disentangle genetic from environmental effects on cognitive performance as assessed with the following measures: Wechsler Adult Intelligence Scale-Revised (WAIS-R), Wisconsin Card Sorting Test, Trail-Making Test, Tower of Hanai, Verbal Fluency Test, Stroop Test, short-term and consolidation memory, and the d2 task. Groups with different genotypes (n = 11 mothers with a full mutation in the FMR-1 gene of fra-X children; n = 65 mothers with a premutation in the FMR-1 gene of fra-X children; n = 18 siblings of these mothers with normal CGG repeats) and with different psychosocial stressors from fra-X families (n = 14 siblings with a premutation but without affected children of their own) were examined. A group of mothers of non-fra-X autistic children (n = 39) formed an external control group. Previous findings were replicated concerning cognitive performance of FMR-1 full-mutation carrier mothers, who were characterized by lower overall IQ and poorer performance than the group of mothers with the FMR-1 premutation in verbal and performance subtests of the WAIS-R, tests of executive-frontal lobe functioning, and tests of sustained attention. Carriers of the FMR-1 premutation, whether they were mothers of affected children or not,performed in a similar way on all neuropsychological tasks to the intrafamilial control group without CGG amplification. On the basis of these results, it is concluded that there is no neuropsychological evidence of reduced cognitive performance of FMR-1 premutation carriers compared with performance of two control groups with normal CGG repeats. Furthermore, the psychosocial burden of raising fra-X children does not exert an environmental effect on neuropsychological test performance.     

Biomolecular-chemical screening: a novel screening approach for the discovery of biologically active secondary metabolites. II. Application studies with pure metabolites

The novel screening strategy called "biomolecular-chemical screening" combines the advantages of the chemical screening approach--the analysis of the chromatographic and chemical behaviour of secondary metabolites on TLC plates--with binding studies of these molecules with bio-macromolecules like DNA. This approach was advantageously used to detect the interaction of pure compounds with DNA. In order to prove the reliability of the biomolecular-chemical screening and to examine DNA-binding properties, 470 pure secondary metabolites were analysed by this method. Besides the confirmation of already known binders with the TLC-based method, for a number of natural products DNA-binding properties were discovered for the first time. In consequence, binding of pure compounds can be measured by 1D TLC in a reliable and easy manner, in which DNA is applied together with the test compound at the starting spot. Analysis is performed via differences in Rf-values in comparison to a reference chromatogram without DNA.     

Characterization of the procoagulant chain derived from human high molecular weight kininogen (Fitzgerald factor) by human tissue kallikrein

Human high molecular weight kininogen (HMWK), a single-chain protein with mol wt 120,000, is cleaved by human urinary kallikrein (HUK) to release kinin from within a disulfide loop and form a two-chain protein that retains all the procoagulant activity of the native molecule. Cleavage of HMWK by HUK is associated with a reduction in size to mol wt 115,000, as assessed by SDS-PAGE of unreduced protein, whereas the two chains of the reduced protein present together as a single broad band with mol wt 64,000. The 64,000 chain with procoagulant activity was chromatographically separated from the nonfunctional chain of similar size. The homogeneous procoagulant chain had an amino acid composition similar to that of smaller procoagulant ("light") chains isolated by others upon cleavage of HMWK with plasma kallikrein and elicited an antiserum that was monospecific by Ouchterlony analysis and inhibited the procoagulant function of HMWK. Thus, the limited proteolysis of HMWK by HUK has permitted, for the first time, the isolation of a stable procoagulant chain that is equal in size to the nonfunctional chain. The common terminology of "heavy" and "light" chain for kinin-free kininogen obtained with plasma kallikrein reflects the continued degradation of the procoagulant carboxyterminal chain and is not appropriate for the initial two-chain product formed when kinin is released from HMWK. It is proposed that the initial cleavage products of HMWK be designated the A-chain, the B-fragment, and the C- chain, representing the amino-terminal chain, the released vasoactive peptide containing the bradykinin sequence, and the carboxy-terminal procoagulant chain, respectively. Thus, intact HMWK would contain, in sequence, A, B, and C regions.     

Acoustic imprinting leads to differential 2-deoxy-D-glucose uptake in the chick forebrain.

This report describes experiments in which successful acoustic imprinting correlates with differential uptake of D-2-deoxy[14C]glucose in particular forebrain areas that are not considered primarily auditory. Newly hatched guinea chicks (Numida meleagris meleagris) were imprinted by playing 1.8-kHz or 2.5-kHz tone bursts for prolonged periods. Those chicks were considered to be imprinted who approached the imprinting stimulus (emitted from a loudspeaker) and preferred it over a new stimulus in a simultaneous discrimination test. In the 2-deoxy-D-glucose experiment all chicks, imprinted and naive, were exposed to 1.8-kHz tone bursts for 1 hr. As shown by the autoradiographic analysis of the brains, neurons in the 1.8-kHz isofrequency plane of the auditory "cortex" (field L) were activated in all chicks, whether imprinted or not. However, in the most rostral forebrain striking differences were found. Imprinted chicks showed an increased 2-deoxy-D-glucose uptake in three areas, as compared to naive chicks: (i) the lateral neostriatum and hyperstriatum ventrale, (ii) a medial magnocellular field (medial neostriatum/hyperstriatum ventrale), and (iii) the most dorsal layers of the hyperstriatum. Based on these findings we conclude that these areas are involved in the processing of auditory stimuli once they have become meaningful by experience.     

Evolutionary analysis of the plastid-encoded gene for the α subunit of the DNA-dependent RNA polymerase of Pyrenomonas salina (cryptophyceae)

The nucleotide sequence of the gene coding for the plastid-encoded subunit of DNA-dependent RNA polymerase from the cryptomonad alga Pyrenomonas salina was determined. The deduced amino-acid sequence, corresponding to a 35.2 kDa polypeptide, was compared to homologues from other organisms. Evolutionary relationships were analyzed in detail by the parsimony method together with bootstrap analysis. The deduced phylogenetic tree shows that the cryptomonad gene is the most ancient type of known plastid-encoded RNA polymerase.     

The concept of major depression

Six operational definitions of the concept of major depression were submitted to empirical evaluation in 600 psychiatric inpatients. Special attention was given to the comparison of major depression in DSM-III-R and ICD-10. The data base created by a polydiagnostic interview revealed relevant classificatory differences between the six definitions under study. Sources of different diagnostic base rates were: inclusion or omission of anhedonia as an obligatory mood criterion; minimal number of syndrome criteria required for the syndrome diagnosis; different width and reference points of time criteria; exclusion rules for co-existing schizophrenic symptoms and for previous nonaffective and manic episodes. The empirically evaluated overlap between pairs of diagnostic definitions was less than excellent in most of the diagnostic definitions under study; only the DSM-III and DSM-III-R definitions agreed with each other to a highly comparable degree. The relatively good agreement of the 1989 draft definition of ICD-10 for major depression ("mild depression") with the other five operational definitions (kappa = 0.69) led us to expect that this definition should receive sufficient international acceptance.     

Cognitive impairments of aphasics in picture sorting and matching tasks

On the basis of earlier experiments showing a differential deficit of aphasics in picture sorting and matching tasks, two experiments were conducted to test the conjecture of a specific deficit of aphasics in the analytical appraisal of individual features. Broca's and Wernicke's aphasics-according to clinical diagnoses and the Aachener Aphasie Test-were compared with patients having right-hemisphere lesions or left-hemisphere lesions without aphasia. Both groups of aphasics differed from the control groups in the sorting task, irrespective of the sorting criterion, but the differences were small. The picture matching task did not discriminate between groups. Obviously, the basic assumption has to be modified with respect to specific conditions of task requirements. The experimental literature is reviewed.This research was supported by a Research Grant from the Deutsche Forschungsgemeinschaft.The research was conducted at the following clinics and rehabilitation centers. We are grateful for their support: Abteilung Neurologie der Med. Fak., RWTH, Aachen. Poliklinik für Stimm-und Sprachkranke, Universitätsklinikum Steglitz, Freie Universität Berlin. Neurologisches Rehabilitationszentrum Godeshöhe e. V., Bonn. Rheinische Landesklinik für Sprachgestörte, Bonn. Neurologische Klinik der Universität Ulm, Dietenbronn. Kliniken Schmieder, Gailingen und Allensbach. Max-Planck-Institut für Psychiatrie, München. Neurologiches Krankenhaus, München. Neurologisches und Hirneverletzten-Versorgungskrankenhaus, Tübingen.We are also most grateful for the kind help of K. Willmes, Aachen, in carrying out the discriminant analyses to classify the aphasics on the basis of the Aachener Aphasie Test.     

Child care workers' development within an interactional perspective: A response to Bayduss and Toscano

Professional development as advocated in the Baydus/Toscano model, primarily conceived as anintra personal emotional maturing process constitutes a rather limited and one-sided perspective. Professional development, especially in child care work, is primarily anchored in the interactional events. The child care worker struggles with complex tasks in a relatively powerless position in order to become a group leader which his or her role demands. Even if professional development is an individual process, the actual chances for development are anchored in the clarity of a person's role expectaions and the available resources and freedom to carry out the necessary tasks associated with the role. The support obtained is not a personal but rather a system issue—namely the degree of actual recognition given within the context of the total staff alignments. Support, in its clearest analysis, is reflected basically through working conditions, receptivity to staff persons' input within their role functions, status, and salary classifications. How dollars for child care work are spent means what kind of support is at hand.This is a companion article to an original position paper by Gregory Bayduss and John A. Tuscano, Child Care Workers Development.     

Zur Reliabilität und Validität der deutschen Version der Prämorbiden Anpassungsskala (PAS)

The Premorbid Adjustment Scale (PAS) was developed by Cannon-Spoor et al. 1982 for research use and has gained importance internationally. This scale is designed to measure the extent of attaining developmental goals premorbidly. The German version is presented here, with first data on the reliability and validity of the scale. In a sample of schizophrenic and schizoaffective patients (n = 86) and healthy parents of the patients (n = 38), DSM-IV diagnosis was made and PAS and Positive and Negative Syndrome Scale (PANSS) data were taken along with information on the course of the disorder. Using Cronbachs alpha, the estimated reliability for the scale and subscales lay between 0.809 and 0.931. High PAS scores, representing poor premorbid adjustment, correlated significantly with low age of onset, high PANSS scores, insidious onset, long hospitalisation, and serious course of the disorder. The threshold of PAS scores between healthy and sick probands was at 0.23. Patients with scores > 0.53 appeared to have an unfavourable course. With test results > 0.23, an odds ratio of 27.9 was ascertained (95% CI 9.39-82.89). The findings presented correspond with those from previous reports in literature.