Steroid receptors and atypical histology as prognostic parameters in meningioma

Cytosolic oestrogen and progesterone receptors (ER and PR) were determined in 58 primary and 13 recurrent meningiomas and related to their histological and clinical features. ER levels were low or not detectable (range 0-34 fmol/mg prot., median 0 fmol), whereas considerable amounts of PR were found in 69% of primary tumours (range 0-583 fmol/mg prot., median 72 fmol) and in 5/5 long-term recurrences (range 69-505 fmol/mg prot., median 143). Eight tumours recurred within a short-term period (less than 5 years) with a low PR expression (range 0-34 fmol/mg prot., median 0 fmol) and all presented raised cellularity and mitotic rate ("atypical" meningioma) or criteria of definitely malignant meningioma. The primary tumours of the short-term recurrences were not available for receptor analysis; however, they also were either "atypical" or anaplastic meningiomas. Long-term recurrences never displayed other than classical histology. From our results we conclude that polymorphy, as well as a lack of PR are strong indicators for short-term recurrence.     

Stress-induced reduction in the rat mixed lymphocyte reaction is due to macrophages and not to changes in T cell phenotypes

Exposure to aversive events or Stressors modulates various aspects of immune function. We have previously reported that exposure to an acute Stressor, inescapable tail shock (IS), resulted in a shift in T cell subpopulations in rat mesenteric lymph nodes but not in cervical lymph nodes (Fleshner et al. (1992) J. Neuroimmunol. 41, 131–142). The mesenteric ratio was increased immediately after exposure to IS and was due primarily to an increase in the percent of CD4⁺ cells. The present experiments were designed to determine the relationship between the IS-associated phenotypic shift and its significance in the function of CD4⁺ T cells. The function assessed was the in vitro proliferative response to alloantigens coded for by the Major Histocompatibility Complex (MHC). Using the mixed lymphocyte reaction (MLR), we report that exposure to IS resulted in a decrease in the MLR response of cells from both cervical and mesenteric lymph nodes. Depletion of macrophages (nylon wool adherent cells) eliminated the IS-induced reduction and co-culture of macrophages (irradiation-insensitive cells) from shocked rats produced the suppression. One interpretation of these data is that exposure to IS resulted in the activation of macrophages and the release of a suppressive factor which reduced the MLR response of peripheral lymph node lymphocytes.     

Excess of high activity monoamine oxidase A gene promoter alleles in female patients with panic disorder

A genetic contribution to the pathogenesis of panic disorder has been demonstrated by clinical genetic studies. Molecular genetic studies have focused on candidate genes suggested by the molecular mechanisms implied in the action of drugs utilized for therapy or in challenge tests. One class of drugs effective in the treatment of panic disorder is represented by monoamine oxidase A inhibitors. Therefore, the monoamine oxidase A gene on chromosome X is a prime candidate gene. In the present study we investigated a novel repeat polymorphism in the promoter of the monoamine oxidase A gene for association with panic disorder in two independent samples (German sample, n = 80; Italian sample, n = 129). Two alleles (3 and 4 repeats) were most common and constituted >97% of the observed alleles. Functional characterization in a luciferase assay demonstrated that the longer alleles (3a, 4 and 5) were more active than allele 3. Among females of both the German and the Italian samples of panic disorder patients (combined, n = 209) the longer alleles (3a, 4 and 5) were significantly more frequent than among females of the corresponding control samples (combined, n = 190, chi2 = 10.27, df = 1, P = 0.001). Together with the observation that inhibition of monoamine oxidase A is clinically effective in the treatment of panic disorder these findings suggest that increased monoamine oxidase A activity is a risk factor for panic disorder in female patients.     

Reasons why trauma surgeons fail to screen for alcohol problems.

BACKGROUND: Alcohol screening and intervention have been recommended as routine components of trauma care but are rarely performed. HYPOTHESIS: An association exists between current screening and counseling practices and the trauma surgeon's knowledge, attitude, and perceived role and responsibility toward alcohol problems. PARTICIPANTS: Random-sample survey (n = 241) of members of the American Association for the Surgery of Trauma. MAIN OUTCOME MEASURES: Reported screening and counseling practices. RESULTS: Fifty-four percent of respondents screened 25% or fewer patients, while only 29% screened most patients. The most common reason for not screening was "lack of time." Most (76%) were not familiar with the most common clinically used screening questionnaires, and 83% reported no training in alcohol screening. Screening was more likely if attending physicians perceived a major responsibility for screening (P<.001). Nonscreeners were twice as likely to state screening was "not what I was trained to do" and more frequently believed screening offends patients (P =.001). Independent predictors of screening were perceived major role responsibility (odds ratio [OR], 2.35; 95% confidence interval [CI], 1.38-4.01) and confidence in screening ability (OR, 1.96; 95% CI, 1.05-3.67) and counseling ability (OR, 2.27; 95% CI, 1.34-3.85). Eighty-eight percent of respondents would be willing to devote time to training if shown that counseling is effective. CONCLUSIONS: Lack of screening and counseling appears to be due to cognitive factors, not lack of motivation. Skills on how to screen and counsel for alcohol abuse should be taught to trauma surgeons, because a strong correlation exists between screening and confidence in skills. There is a need for education regarding results of effective intervention trials in medical settings.     

Wiederholung und Iteration Von der Psychoanalyse zur Systemtheorie

Starting with Freud's presentation in "Beyond the Pleasure Principle", the conception of the repetition compulsion is introduced. Freud gave a teleological interpretation of the psychological phenomenon of repetition. On one hand, he considered it as an attempt of the psyche to get delayed control over a penetrating amount of traumatic stimuli, on the other hand, he interpreted it within his conception of death instinct as an expression of a destructive impulse. From systems theory, especially from chaos theory originates the conception of iteration. It is used to describe systems characterized by repeatedly performed operations representing simultaneously an important model of homeostatic regulation in living systems. The applicability of the iteration conception on repetition phenomena in the psychic field is being discussed. With reference to Luhmann's systems theory, repetition can be considered as an iterative phenomenon within the selfreferencing organization of the psyche. However the connection between physiological processes in the nervous system and psychological phenomena is not ascertainable, especially not from the point of view of systems theory. Conceptions of systems theory being transferred to the psychic field represent a hermeneutic approach to the matter.     

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.