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.     

Systematic screening for DNA sequence variation in the coding region of the human dopamine transporter gene (DAT1)

The dopamine transporter (DAT) plays a central role in dopaminergic neurotransmission in the human brain. Genetic association studies have used a variable number of tandem repeat (VNTR) polymorphism in the 3'-flanking region of the dopamine transporter gene (DAT1) to implicate the DAT in the development of various neuropsychiatric disorders. In this study, we have examined the possibility that a mutation exists in the coding region of the DAT1 gene which through linkage disequilibrium accounts for the observed associations. The complete coding region, as well as exon-intron boundaries, was screened in 91 unrelated individuals including 45 patients with bipolar affective disorder and 46 healthy control individuals by the means of single strand conformation analysis. Our findings suggest that the DAT1 gene is highly conserved since we detected only two rare missense substitutions (Ala559Val, Glu602Gly) and three silent mutations (242C/T, 1342A/G, and 1859C/T) in the whole coding region. Five sequence variants were observed in intronic sequences but none affects known splice sites. The lack of frequent variants of possible functional relevance indicates that genetic variation in the coding region of the DAT1 gene is not responsible for the previously observed associations with neuropsychiatric disorders. The two rare missense substitutions were found in single bipolar patients but not in controls. Investigation of the patients' families revealed independent segregation between the Ala559Val variant and affective disorder. The Glu602Gly variant was inherited by the proband from an affected father. It therefore remains possible that Glu602Gly may be a rare cause of bipolar affective disorder.     

Confirmation of the association between bleomycin hydrolase genotype and Alzheimer's disease

Bleomycin hydrolase (BH), a cysteine protease from the papain superfamily, is considered to be a candidate for the beta-secretase, which is presumably involved in the production of beta-amyloid peptide. The G/G genotype of BH was identified as a significant risk factor for the development of Alzheimer's disease (AD) in subjects not carrying the apolipoprotein E epsilon4 allele (apoE-epsilon4). However, this finding was recently challenged. We studied this polymorphism in a homogenous sample of German AD patients and controls. The over-representation of the G/G genotype in AD patients could be confirmed, however it was more pronounced in apoE-epsilon4 carriers. Additional studies should be undertaken to increase the confidence that the BH polymorphism is associated with AD and to explore the relationship between BH and apoE.