Lycobetaine acts as a selective topoisomerase II beta poison and inhibits the growth of human tumour cells.

The phenanthridine alkaloid lycobetaine is a minor constituent of Amaryllidaceae. Inhibition of cell growth was studied in the clonogenic assay on 21 human tumour xenografts (mean IC(50) = 0.8 microM). The growth of human leukaemia cell lines was also potently inhibited (mean IC(50) = 1.3 microM). Athymic nude mice, carrying s.c. implanted human gastric tumour xenograft GXF251, were treated i.p. with lycobetaine for 4 weeks, resulting in a marked tumour growth delay. Lycobetaine was found to act as a specific topoisomerase II beta poison. In the presence of calf thymus DNA, pure recombinant human topoisomerase II beta protein was selectively depleted from SDS-gels, whereas no depletion of topoisomerase II alpha protein was observed. In A431 cells immunoband-depletion of topoisomerase II beta was induced, suggesting stabilization of the covalent catalytic DNA-intermediate in living cells. It is reasonable to assume that this mechanism will cause or at least contribute significantly to the antitumour activity.

[Ernst Schweninger, personal physician of the German chancellor and director of the Charite Dermatology Clinic 1884-1902]. / Ernst Schweninger, Leibarzt des Reichskanzlers und Direktor der Charité-Hautklinik 1884-1902.

Ernst Schweninger was at the age of 33 years already world renowned for being Bismarck's personal physician. In 1884, his grateful patient made him chief of the Department of Dermatology in Berlin and Professor of Dermatology. The subsequent years were marked by political struggles within the university, but he still produced a number of scientific publications, and is still remember for his first description of anetoderma type Schweninger-Buzzi. Dermatology and his activities at the Berlin clinic from whose direction he resigned in 1902 accounted for only one period in his life. His main interest was the physiologic-dietetic therapeutic method which he applied also to dermatology. Later on, he dissociated himself from scientific medicine and became the founder of a school for natural healing methods. The present report is designed to keep alive the memories of this politically active physician.

Active DNA topoisomerase IIalpha is a component of the salt-stable centrosome core.

Recently, we reported that the monoclonal antibody specific for human DNA topoisomerase IIalpha, Ki-S1, stains not only the nuclei of human A431 cells but also extranuclear structures suggestive of centrosomes (Meyer, K. N., Kjeldsen, E., Straub, T., Knudsen, B. K., Kikuchi, A., Hickson, I. D., Kreipe, H., and Boege, F. (1997) J. Cell Biol. 136, 775-788). Here, we confirm colocalization of Ki-S1 with the centrosomal marker gamma-tubulin. In addition, we show labeling of centrosomes by peptide antibodies against the N and C termini of human topoisomerase IIalpha. Probing Western blots of isolated centrosomes with topoisomerase IIalpha antibodies, we demonstrate a protein band of 170 kDa. Moreover, isolated centrosomes exhibited DNA decatenation and relaxation activity correlated to the amount of topoisomerase IIalpha protein in the same way as seen in the pure recombinant enzyme. Topoisomerase IIalpha epitopes could not be removed from centrosomes by salt extraction, DNase treatment, or RNase treatment, procedures that completely removed the enzyme from nuclei. Taken together, these observations suggest that active topoisomerase IIalpha is bound tightly to the centrosome in a DNA-independent manner. Because such centrosomal topoisomerase IIalpha was also present in quiescent lymphocytes devoid of topoisomerase IIalpha in the nuclei, we assume that it might be a long-lived storage form.

Detection of autoantibodies against tissue transglutaminase in patients with celiac disease and dermatitis herpetiformis.

OBJECTIVE: Endomysial autoantibodies (EmA) are specific for celiac disease. The target antigen has been identified as tissue tranglutaminase (tTG). Our aim was to study the accuracy of a newly developed enzyme-linked immunosorbent assay (ELISA) for easy detection of tTG autoantibodies. METHODS: Thirty-one sera from patients with histologically proven celiac disease and 23 healthy controls were examined for EmA using monkey esophagus and human umbilical cord as substrate. IgA-tTG autoantibodies were determined by newly developed ELISA. Additionally, sera from patients with dermatitis herpetiformis (n = 20), inflammatory bowel disease (IBD; n = 32), chronic liver disease (n = 36), and diabetes mellitus (n = 19) were tested. RESULTS: The sensitivity of the tTG autoantibody ELISA accounted for 90% detection in patients with untreated celiac disease. The specificity was 76% owing to positive values in the lower range in patients with IBD (15%), chronic liver disease (36%), and diabetes (22%), all of whom were negative for EmA. In dermatitis herpetiformis patients 90% were EmA-positive. Of these, only 47% showed elevated tTG autoantibodies. Preincubation of sera from dermatitis patients with tTG abolished immunofluorescent staining of endomysial structures. CONCLUSION: Detection of mid- to high-titer tTG autoantibodies is highly specific for celiac disease. However, in the low-titer range, overlap exists with liver disease, IBD, and diabetes. Tissue transglutaminase autoantibodies may evolve as a new screening and follow-up method for celiac disease. Although tTG seems to be a major autoantigen in dermatitis herpetiformis, the low sensitivity of both tTG ELISA and immunofluorescence using human umbilical cord suggests differential involvement of tTG in this disease.

Beware of the heart: the multiple picture of cardiac involvement in myositis.

A 42-yr-old woman with dermatomyositis had two myocardial infarctions, episodes of acute chest pain and an acute lung oedema. These events were initially misinterpreted as atherosclerotic ischaemic heart disease accompanying the autoimmune disease. The lack of improvement of cardiac symptoms with anti-ischaemic and immunosuppressive drugs indicated other mechanisms. Intracoronary drug provocation as well as myocardial biopsy revealed a coincidence of small-vessel disease and vasospastic angina as a cause for the severe cardiac symptoms. After initiating therapy with high doses of calcium channel blockers, marked improvement of cardiac symptoms occurred. In the pathogenesis of cardiac involvement in dermatomyositis, two different mechanisms should be considered: inflammatory processes due to dermatomyositis and vasoconstriction caused by an impaired regulation of vascular tone, such as abnormal vessel reactivity or disturbed neuropeptide release. Signs of this generalized vasopathy are Raynaud's phenomenon, Prinzmetal's angina and small-vessel disease, which can coincide. In patients with severe cardiac symptoms and autoimmune diseases, Prinzmetal's angina should be excluded by intracoronary drug provocation using acetylcholine.

Penetration of titanium dioxide microparticles in a sunscreen formulation into the horny layer and the follicular orifice.

Coated titanium dioxide (TiO2) microparticles are commonly used as UV filter substances in commercial sunscreen products. The penetration of these microparticles into the horny layer and the orifice of the hair follicle was investigated. The distribution of the microparticles in the horny layer was analyzed using the method of tape stripping in combination with spectroscopic measurements. Deeper layers of the stratum corneum were devoid of TiO(2) even after repetitive application of sunscreen preparation when analyzing interfollicular areas. Only in the areas of the pilosebaceous orifices could microparticles be identified. The penetration of TiO(2) was investigated in histological skin sections. A biopsy was taken from a skin area from which the horny layer had been removed by tape stripping. In isolated areas, a penetration of coated TiO2 into the open part of the follicle was observed. The amount of TiO2 found in a given follicle was less than 1% of the applied total amount of sunscreens. A penetration of microparticles into viable skin tissue could not be detected.

The Biographical Personality Interview (BPI)--a new approach to the assessment of premorbid personality in psychiatric research. Part I: Development of the instrument.

The Biographical Personality Interview (BPI) is a research instrument for the retrospective assessment of premorbid personality traits of psychiatric patients. Its construction is based on results of a series of investigations in which biographical data from psychiatric case notes were analysed with respect to premorbid personality traits. In order to avoid methodological shortcomings of the utilisation of clinical records, an interview technique was developed. It is applied by two independent, specially trained investigators who are kept "blind" regarding any clinical data of the subject under study. One of them has to conduct the interview of a clinically remitted patient and to provide an interview protocol, the other one has to rate personality traits from that protocol along a large series of purely descriptive items. Sum scores for six personality structures ("types") are calculated and the case is then assigned to the intra-individually dominating personality type according to the highest of these scores.

The Biographical Personality Interview (BPI)--a new approach to the assessment of premorbid personality in psychiatric research. Part II: Psychometric properties.

The Biographical Personality Interview (BPI) was applied to 179 subjects (158 psychiatric patients and 21 probands from the general population); 100 patients and 20 healthy controls served as a validation sample; the others had been interviewed during the training period or did not meet the inclusion criteria for the validation of the BPI. The acceptance of the interview was high, the inter-rater reliability of the ratings of premorbid personality structures ("types") varied between 0.81 and 0.88 per type. Concurrent validity of the typological constructs as assessed by means of the BPI was inferred from the intercorrelations of type scores and correlations of these scores with questionnaire data and proved to be adequate. Clinical validity of the assessment was indicated by statistically significant differences between diagnostic groups. Problems and further developments of the instrument and its application are discussed.

An operationalized procedure for the recognition of premorbid personality types in biographical case notes on psychiatric patients.

A method for the assessment of six premorbid personality types from biographical data in psychiatric case histories is described. Trained raters have to fill in a list comprising 106 items as descriptors of a patient's premorbid behavioural development. The assignment to the types in question (the "manic type" and its rare variant, the "happy-go-lucky type", the "melancholic type", the "anxious insecure type" and its rare variant, the "unrealistic dreamy type", and finally, the "nervous tense type") is computed on the basis of the item scores by forming type scores and comparing their height intraindividually. The subject under study is assigned to the type reaching the comparatively highest value. Two raters independently analyzed 261 records from which all information on mental disorders in family members and the patient himself/herself as well as all biographical data from the first manifestation of a symptom disorder onwards had been erased by technical assistants. In 106 of the records, a global assignment to the types of premorbid personality had already been performed by one of the authors of the typology. The scores for the same type assessed by the two ratings correlated highly with each other (0.77 to 0.80), the concordance of types reached a kappa-value of 0.55 (P < 0.001), and the results of the operationalized typing agreed in the same order with the result of global typing in the subsample of n = 106.(ABSTRACT TRUNCATED AT 250 WORDS)

[Percutaneous absorption of hematoporphyrin derivative--fluorescence- and electron microscopic studies]. / Perkutane Absorption von Hämatoporphyrin-Derivat--Fluoreszenz- und elektronenmikroskopische Untersuchungen.

Using surviving human skin, percutaneous absorption following topical application of hematoporphyrin derivative was investigated. Hematoporphyrin derivative gave strong red fluorescence, which was dependent from it's actual concentration, from the used kind of vehicle, from preparation time, and from time between preparation and application of hematoporphyrin derivative solution. Ultrastructural investigation verified cytoplasmatic membranes and mitochondria as the principal targets also after topical application followed by irradiation with visible light.

[The value of humoral immune phenomena in children and adolescents with circumscribed scleroderma]. / Zum Aussagewert humoraler Immunphänomene bei Kindern und Jugendlichen mit zirkumskripter Sklerodermie.

Sera taken from 35 children and teen-agers with different clinic variants of the circumscribed scleroderma were investigated for the presence of FANA, anti-DNA-, anti-DNP-, anti-ENA-(extractable nuclear antigens)-, and anti-Ro/SSA-antibodies. In 85.7% of the patients, humoral immune phenomena were ascertainable. Whereas FANA above all in patients with clinically rapidly progredient running linear form (71%) were present, anti-dsDNA- and anti-DNP-antibodies may be worth as hint upon a visceral manifestation. Therefore, they may be valid as leading antibodies for a subset of the circumscribed scleroderma, which is being designated by extracutaneous participation and the skin mostly exhibit a linear variant. The frequency of the evidence of the characteristic immune phenomena in patients with circumscribed scleroderma, which are typically in systemic lupus erythematosus, is considered as hint to the immune pathogenesis of the disease. The functional defects of the kidneys, catched with the isotope-clearance refer to a possible systemic character of the disease-process. Humoral immune phenomena are suitable for differentiation of the cutaneous and extracutaneous progress forms, in which high titer of FANA with homogeneous pattern of fluorescence, anti-dsDNA- and anti-DNP-antibodies have a special importance. Compared to it anti-ssDNA-antibodies and anti-Ro/SSA-antibodies characterize the high degree of activity of cutaneous and extracutaneous progress forms.

Correlation between the phenotype and the functional capacity of activated T cells in patients with active systemic lupus erythematosus.

Activated T cells in the peripheral blood of patients with systemic lupus erythematosus (SLE) were determined using monoclonal antibodies against activation antigens. Elevated percentages of HLA-DR+ T cells were found in association with active disease. In contrast, we observed an increase in IL-2 receptor-bearing T cells in only six out of 16 patients with active disease. In vitro assays, like spontaneous proliferation, response to IL-2, production of IL-2, and immunoglobulin synthesis have shown that the different patterns of activation antigens are related to different functional stages of T-cell activation. The possible therapeutic consequences are discussed.