Complement-mediated enhancement of HIV-1 neutralisation by anti-HLA antibodies derived from polytransfused patients

We have recently shown that 'alloimmune sera' derived from polytransfused patients (PTP sera) are able to recognise and neutralise HIV in vitro. In this study we try to identify the protein(s), which are recognised by the PTP sera and elucidate mechanisms responsible for the neutralising capacity of these sera. The PTP sera allowed immunoprecipitation (IP) of HLA class II molecules on HIV-infected cells. To detect a potential cross-reactivity of alloreactive antibodies (Ab) with the HIV envelope protein gp160 or its subunits gp120/gp41 and HLA proteins, ELISA and FACS analyses were performed. The lack of reactivity of the PTP sera against rsgp160 in ELISA or FACS analysis indicated that recognition of cells was independent of HIV infection. To clarify whether interaction of the PTP sera with target cells has any effect on the infection process, virus neutralisation assays were performed. Inhibition of HIV infection was observed only when virus was pre-incubated with the PTP sera. Complement enhanced neutralisation of HIV-1 significantly. This enhancement was not due to complement-mediated lysis, because pre-incubation of the target cells with PTP sera did not inhibit HIV replication. Therefore, the neutralising effect of the Ab was due to blocking of the viral attachment/fusion process and not to negative signalling after infection. Since steric hindrance is possible only when HLA and gp120/gp41 are in close vicinity, isolation of rafts and IP assays were performed. These experiments revealed that gp120 and MHC class II molecules are indeed co-localised. The close physical association of gp120/gp41 and HLA strongly supports a mechanism for neutralisation of HIV by anti-HLA-Ab based on steric hindrance.     

Hepatocellular Hyperplasia, Plasmacytoma Formation, and Extramedullary Hematopoiesis in Interleukin (IL)-6/Soluble IL-6 Receptor Double-Transgenic Mice

Cytokines interact not only with membrane anchored receptors, but also with specific soluble receptors which circulate in the bloodstream. In general, soluble cytokine receptors such as soluble tumor necrosis factor receptor, soluble interleukin 1 receptor, and soluble interleukin 4 receptor compete with their membrane-bound counterparts for the ligands and therefore act as antagonists. In contrast, soluble receptors for cytokines of the interleukin-6 (IL-6) family complex with their ligands act agonistically. Interestingly, the complex of IL-6 and the soluble interleukin 6 receptor (sIL-6R) activates target cells that do not express the membrane-bound IL-6R and therefore cannot respond to IL-6. To identify cellular responses that are due to IL-6/sIL-6R but not to IL-6 alone, IL-6/sIL-6R double-transgenic mice were generated and compared with IL-6 single-transgenic mice. IL-6/sIL-6R transgenic mice develop a severe phenotype showing 1) marked hepatocellular hyperplasia frequently surrounded by peliosis and necrosis, 2) significant acceleration and aggravation of plasmacytoma formation, and 3) excessive activation of extramedullary hematopoiesis in spleen and liver followed by a subsequent increase of all cellular components in the peripheral blood. These in vivo data suggest that the sIL-6R recruits primarily unresponsive cell populations such as hematopoietic progenitor cells and hepatocytes to IL-6-induced proliferation, but also enhances the known mitogenic effect of IL-6 on plasma cells and thereby contributes to plasmacytoma formation.     

Effect of surface treatment on the shear bond strength of three resin cements to a machinable feldspatic ceramic

The aim of this study was to evaluate the shear bond strength of three resin cements to Vita Mark II ceramics under different pretreatments of the ceramic surface and to examine whether simplified pretreatment procedures would result in satisfying results compared to the state of the art. RelyX Unicem (RXU), Calibra (CAL), and Variolink II (VAR) were used as resin cements and bonded to machine milled feldspatic disks, pretreated in five different ways. (1) no pretreatment of the ceramic surface; (2) surface etched with hydrofluoric acid (HF); (3) ceramic surface silanized; (4) ceramic surface etched (HF) and silanized, (5) ceramic surface etched (HF), silanized, and covered with Heliobond. The shear bond strengths were measured initially, after 5000 and 10,000 thermocycles (TC). After 10,000 TC for CAL only procedure 5 resulted in a reliable adhesion median value of 10.7 MPa. VAR showed median values of 24.6, 17.2, and 18.1 MPa for pretreatments 5, 3, and 4, respectively. RXU performed 25.9, 22.0, and 11.0 MPa for procedures 5, 4, and 3, respectively. For procedure 2, RXU revealed the significantly highest value with 15.4 MPa (U-test, p = 0.05). Only RXU-luted specimens of procedure 1 survived the 10,000 thermocycles. The results revealed that a simplification of the ceramic pretreatment for VAR and RXU might be possible.     

Alternating copolymerization of butadiene and propene with the catalyst VO(ONeo)2 Cl/Al(i-C4H9)3, 1

The influence of basic reaction parameters—the ratio of catalyst components, the composition of the monomer mixture and the temperature—on the progress of the copolymerization, the molecular weight and the molecular weight distribution as well as on the composition of the copolymers obtained is reported. Conversion data for the variation of the mole ratio of comonomers show a maximum for an [Al]/[V] mole ratio of approximately 7, whereas the molecular weight of copolymers is not significantly influenced. An increase in the molecular weight of the copolymers can be obtained by an increase of butadiene content in the monomer mixture. However, there is also an increasing incorporation of butadiene into the copolymer. Raising the temperature from ?60°C to 0°C results in a significant decrease in molecular weight, whereas the composition of the copolymers is not significantly changed.     

Morphological detection and quantification of lipoprotein(a) deposition in atheromatous lesions of human aorta and coronary arteries

Summary Lipoprotein(a), as an atherogenic particle, represents an independent risk factor for coronary heart disease. In the present study the morphological distribution of apoprotein (a) and apoprotein B within the arterial wall is described. Apoprotein B, a constituent of very low-density lipoprotein, low-density lipoprotein and lipoprotein(a) has previously been demonstrated in atheromatous lesions. Lipoprotein(a) possesses an additional protein, designated apoprotein (a). Autopsy material (n=74) from the left coronary artery and from the thoracic aorta has been examined by means of immunohistochemistry and both apoprotein (a) and apoprotein B were detected, primarily associated with the extracellular matrix and accumulating in lesions in the arterial wall. The staining pattern for both antigens was almost always found to be congruent, suggesting that the detection of (a)-antigen has to be attributed at least in part to the presence of lipoprotein(a). It is concluded that both low-density lipoprotein and lipoprotein(a) have an important role in the pathogenesis of atherosclerosis.     

Thermogenic effect of adrenaline: interaction with insulin

Summary The contribution of insulin (3.6 pmol sd kg body mass^–1·min^–1 to adrenaline-induced (0.164 nmol · kg fat free mass^–1·min^–1) thermogenesis was studied in ten postabsorptive healthy volunteers using two sequential protocols. Variables considered were oxygen consumption as well as carbon dioxide production, heart rate, blood pressure, plasma concentrations of glucose, insulin, glycerol, free fatty acids,-HO-butyrate and lactate. Adrenaline increased plasma concentrations of glucose, glycerol, free fatty acids, and-HO-butyrate, and heart rate and metabolic rate during normo-insulinaemia [61.3 (SEM 6.6) pmol·^–1]. Similar effects were observed during hyperinsulinaemia [167.9 (SEM 18.7) pmol·^–1], but the effect of adrenaline on oxygen consumption was reduced. On average, metabolic rate increased by 12.9% during normo-insulinaemia and by 8.9% during hyperinsulinaemia. We concluded that relative hyperinsulinaemia resulted in decreased adrenaline-induced thermogenesis and therefore increased whole body anabolism.     

Structural analysis of alkene/maleic anhydride copolymers

Structural investigations on maleic anhydride (MAn) copolymers with ethene, propene and styrene, their products of hydrolysis, and their methyl half-esters by means of ¹³C NMR spectroscopy are presented. The spectra of 2,3-diethylsuccinic acid and its anhydrides in the erythro- and threo-configuration and of butylsuccinic acid and its anhydride were obtained and compared with the spectra of the copolymers. In each case the results show the formation of both threo(trans)- and erythro(cis)-structures. At a polymerization temperature of 60°C the proportions were 88% threo to 12% erythro for ethene/MAn copolymers and 80% threo to 20% erythro for propene/MAn copolymers, a ratio which was confirmed also by the hydrolyzed forms. Copolymerization at 150°C leads, in the case of propene/MAn, to 67% threo and 33% erythro. The production of ethene/MA copolymer via the copolymerization of ethene and fumaric acid half-ester and its saponification to ethene/fumaric acid leads to a ratio of 38% threo to 62% erythro. These results are in accordance with the thermal stabilities of the configurations. In the case of styrene/MAn copolymer it is not possible to obtain a unique interpretation of the configurations from the spectra. For the conversion of propene/MAn and styrene/MAn copolymers by means of methanol to half-esters it can be derived from the ¹³C NMR spectra how many of the half-ester moieties are obtained in the neighbourhood of the methyl and phenyl groups, respectively, of the olefin.     

The effect of erroneous responses on response monitoring in patients with major depressive disorder: a study with event-related potentials

Perceived failure is reported to have detrimental effects on subsequent performance in patients with major depressive disorder. We investigated the error-related negativity (ERN)/error negativity (Ne), an electrophysiological correlate of response monitoring, using a 64-channel EEG. Sixteen patients with DSM-IV major depressive disorder and 16 matched controls participated in an Eriksen flanker task with continuous performance feedback that signaled monetary reward. Compared to controls, patients with major depressive disorder showed a less negative ERN/Ne in error trials following error trials. This result might reflect impaired response monitoring processes in major depressive disorder resulting from an underactivity in a central reward pathway and/or a deficit in strategic reasoning.     

Comparative genomic hybridization analysis of hepatoblastoma reveals high frequency of X-chromosome gains and similarities between epithelial and stromal components

Hepatoblastoma (HB) is the most common liver tumor in childhood and differs in its environmental risk factors and genetic background from hepatocellular carcinoma. HB is associated with inherited conditions such as familial adenomatous polyposis and Beckwith-Wiedemann syndrome, suggesting the importance of genetic abnormalities in the pathogenesis and progression of this disease. It has a very polymorphous morphology. A diverse range of cytogenetic alterations has been reported to date, the most frequent being trisomy 2 and trisomy 20. Thirty-five HB specimens from 31 patients (22 purely epithelial, 4 purely mesenchymal, 9 mixed) were examined by comparative genomic hybridization (CGH), a technique that enables us to screen the entire tumor genome for genetic losses and gains. Our aims were as follows: (1) to characterize chromosome abnormalities that appear in this tumor and (2) to identify possible differences between different histologic subtypes of HB. We found significant gains of genetic material, with very little difference in the number and type of alterations between the different histologic components of HB. The most frequent alterations were gains of Xp (15 cases, 43%) and Xq (21 cases, 60%). This finding was also confirmed by fluorescent in situ hybridization performed on nuclei extracted from 6 specimens. Other common alterations were 1p-, 2q+, 2q-, 4q-, and 4q+. We found no difference between different histologic subtypes, a finding that may be in agreement with the hypothesis of a common clonal origin for the different components. An hitherto-unreported high frequency of X chromosome gains may support the assumption that X-linked genes are involved in the development of this neoplasm.