Modulation of interferon-gamma-induced major histocompatibility (MHC) and CD14 antigen changes by lipophilic muramyltripeptide MTP-PE in human monocytes

The lipophilic muramylpeptide derivative muramyltripeptide-phosphatidylethanolamine (MTP-PE, 0.05 to 5 micrograms/ml) and human recombinant interferon-gamma (rIFN-gamma, 1 to 100 U/ml) were applied singly or in combination to fresh human mononuclear blood leucocytes in vitro. After 15 to 72 hr incubation, culture- and drug-induced changes in beta 2-microglobulin (MHC class I associated), HLA-DR (MHC class II), and Leu-M3 (CD14) antigen expression were investigated by flow cytometry; changes in monocyte morphology (forward light scatter and side scatter) were assessed by scatter analysis. It was found that (1) rIFN-gamma caused a simultaneous down-regulation of the CD14 antigen and an up-regulation of MHC class I and class II molecules on the surface of cultured monocytes; (2) MTP-PE, which by itself failed to influence the expression of these antigens, synergized with rIFN-gamma in increasing MHC antigens and reducing CD14; (3) at high concentrations rIFN-gamma reduced monocyte viability to a small but significant extent and this effect was further potentiated by MTP-PE; and (4) untreated monocytes in culture showed an apparently MTP-PE-insensitive increase in size, density, and beta 2-microglobulin, HLA-DR, and CD14 antigen expression. The influence of MTP-PE on rIFN-gamma-induced surface marker changes may contribute to its immunoadjuvant activity in vivo.     

Stereology in the extraction of information from images

Some important aspects for information extraction by stereology from images in surgical and experimental pathology are discussed. The relationship between stereology and morphometry is briefly discussed, with the most important conditions for stereologic analysis in pathology pointed out. The possibilities, limits and problems inherent in stereologic and morphometric analysis in pathology are explained in two examples: so-called "small airways disease" and tight junctions of hepatocytes during physiologic choleresis.     

Relationship between soluble tumor necrosis factor (TNF) receptors and TNFα during immunotherapy with interleukin-2 and/or interferon α

Eleven metastatic cancer patients were studied during three different regimens of immunotherapy with interleukin-2 (IL-2) and/or interferon (IFN): group A received 4 days of IL-2 i.a. infusion (n=3), group B IFN s.c. during 5 days (n=4), followed on day 3 by 5 days of a continuous IL-2 i.v. infusion, and group C had 4 days of IL-2 i.v. infusion together with s.c. IFN on days 1 and 4 (n=4). Soluble tumor necrosis factor receptors (sTNFR) p55 and p75 and TNF concentrations in serum were analyzed before therapy and daily during 8 days of the first therapy cycle. sTNFR was measured by radioimmunoassay. sTNFR p55 increased in all patient groups from a baseline value of 5.2±0.9 ng/ml to a maximum of 13.6±1.2 ng/ml by days 3–4 (P=0.003). sTNFR p75 increased from 7.6±1.1 ng/ml to peak values of 30.1±2.6 ng/ml in groups A and B (P=0.02). In group C the sTNFR p75 response was weak (NS). In group B, the increase of both p55 and p75 occurred only after addition of IL-2 to IFN. TNF increased weakly during treatment with IFN alone (group B); it rose strongly during IL-2 and the combined treatment (groups A-C) from 8±2 pg/ml to 115±13 pg/ml (P=0.003). In group B, it reached the maximum 24 h after addition of IL-2 to IFN and decreased thereafter. there was a significant relationship between TNF and sTNFR p55 or sTNFR p75 in groups A and C, (P=0.001), but not in group B. Group C was also investigated during the third therapy cycle. The increase of sTNFR p75 was stronger (P=0.01) and that of TNF weaker than in the first cycle; the sTNFR p55 response was similar in both cycles. In conclusion sTNFR p55 and p75 are rapidly induced during IL-2 and IL-2+IFN treatment, the increase of sTNF receptors parallels or exceeds that of TNF and may influence the immunomodulatory effects of TNF during cytokine therapy.     

Territory Defence in Black Redstarts,Phoenicurus ochruros: Effects of Intruder and Owner Age?

European black redstarts, Phoenicurus ochruros, vigorously defend all-purpose territories and exhibit delayed plumage maturation, most subadult males looking exactly female-like in their first breeding season. We tested the hypotheses that such dull subadult male plumages are beneficial in order to reduce aggression of adult males either by deception or by honest signalling of subordinance status, and that, in turn, conspicuous (adult) plumage colorations are able to intimidate contenders because they act as a signal of fighting ability and aggressive motivation. Adult and dull yearling black redstart territory owners were confronted with intruders mimicked by stuffed mounts of either a conspicuous adult or a dull subadult male. Our results do not support the hypotheses tested: dull plumages of young intruders did not reduce aggression from adult territory owners and aggressiveness towards intruders was significantly higher in yearling territory owners as compared with adult owners. Conspicuous intruders did not deter dull territory owners and we found no indications that conspicuous male coloration is a signal of fighting ability or aggressive motivation in this species. Instead, the amount of aggressive response to intruders showed considerable individual variance within age classes regardless of the plumage of the intruder and the status of the owner.     

The CD44 standard/ezrin complex regulates Fas-mediated apoptosis in Jurkat cells

The transmembrane receptor CD44 conveys important signals from the extracellular microenvironment to the cytoplasm, a phenomena known as “outside-in” signaling. CD44 exists as several isoforms that result from alternative splicing, which differ only in the extracellular domain but yet exhibit different activities. CD44 is a binding partner for the membrane-cytoskeleton cross-linker protein ezrin. In this study, we demonstrate that only CD44 standard (CD44s) colocalizes and interacts with the actin cross-linkers ezrin and moesin using well-characterized cell lines engineered to express different CD44 isoforms. Importantly, we also show that the association CD44s-ezrin-actin is an important modulator of Fas-mediated apoptosis. The results highlight a mechanism by which signals from the extracellular milieu regulate intracellular signaling activities involved in programmed cell death. Electronic supplementary material The online version of this article (doi: ) contains supplementary material, which is available to authorized users.     

Habitatpr?ferenzen, Dynamik der Raumnutzung und Bestandsstruktur bei Dorfamseln (Turdus merula)

Zusammenfassung In fünf Montandörfern bei Innsbruck/Tirol und zwei Probeflächen der Stadt wurde der Bestand der Amsel in 2 Winterhalbjahren und 2 bis 6 Brutperioden 1982–1987 untersucht. Die Siedlungsdichte nahm von bäuerlichen Dörfern höherer Montanlagen bis in Stadtbereiche Innsbrucks stark zu und zeigte deutliche Beziehungen zur Länge der Strauchschichtgrenzlinie in den einzelnen Probeflächen. Die Reviere waren sowohl in den städtischen als auch dörflichen Untersuchungsarealen sehr inhomogen verteilt. In den Dörfern wurden ältere Gartensiedlungen deutlich präferiert; zentrale Bauerndorfkerne waren am dünnsten besiedelt. Die Brutbestandsfluktuationen waren in zwei über 6 Jahre kontrollierten Dörfern insgesamt gering (9–15% Variationskoeffizient). Hingegen verdreifachte sich die Zahl der Amselreviere im Teilbereich eines Dorfes im Zuge zunehmender Durchgrünung von 1982 bis 1987. In der Nachbrutzeit gab es grundsätzliche Unterschiede in der Dynamik dörflicher und städtischer Amselpopulationen. Mit zunehmend urbanem Siedlungscharakter nahm offensichtlich nicht nur die Amplitude der saisonalen Bestandsoszillationen ab, sondern auch der Anteil von Standvögeln und insbesondere überwinternder Weibchen zu. Innerhalb der Dorflandschaften wechselte die Nutzungsintensität nahe benachbarter Teilareale kurzfristig und kleinräumig. Vor allem vom Herbst zum Winter waren Präferenzwechsel zwischen randlichen Gartensiedlungen und Obstanlagen und zentraleren, bäuerlichen Dorfbereichen auffällig.

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Habitat preferences and seasonal dynamics of space atilization in Blackbirds (Turdus merula) living in villages

Summary Between 1982 and 1987, habitat selection, seasonal changes in population densities and microspace use as well as fluctuations of breeding populations of the Blackbird were investigated in five mountain villages near Innsbruck, Tyrol. Results are compared with data from two city plots. The breeding density of Blackbirds increased dramatically (tenfold) from farmhouse dominated villages to suburbanlike village plots and to urban areas in the city of Innsbruck. There was a distinct relationship between the number of territories and the length of shrub layer boundaries. Remarkable differences in density existed between structurally different parts of the sample plots. These differences also correlated with the amount of vegetation cover available but were also related to other features of village subareas (e.g. density and character of buildings). The fluctuations of population levels within six years were surprisingly low in two villages (coefficients of variation 9 to 15%). In parts of one village, however, the number of blackbird territories tripled with an increase of the vegetation cover at the same time. In postbreeding season fundamental differences in the dynamics of village and suburban to urban populations were noticed. This is true for the amount of the population oszillations (lower with increasing urbanization) as well as for sex ratio in wintering populations (higher proportions of femals in suburban and city plots). Short-term shifts in habitat preferences were obvious within the village plots in the course of the year. Whereas orchards and older residential areas with rich shrub and tree layers at the village edges were heavily utilized by Blackbirds in autumn, the village centres were preferred in winter.

     

The inhibition of trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate and 4'-nitrobenzyl 4-guanidinobenzoate

The inhibition of the enzymes trypsin, plasmin, and thrombin by benzyl 4-guanidinobenzoate and 4'-nitrobenzyl 4-guanidinobenzoate is caused by acylation of the active site. Second order rate constants were determined.