Zur Geschichte der Anti-Aliens-Bewegung in England

N. W. Goldstein

Characterization of anti -sulfatide autoantibodies in demyelinating diseases

Multiple sclerosis (MS) is the most common autoimmune disease of the central nerve system and Guillain Barré Syndrome (GBS) is an inflammatory neuropathy involving the peripheral nerves. Anti-myelin immunoglobins may play a role in the demyelination processes of the both diseases. Sulfatide is an abundant glycolipid on myelin and is a candidate target antigen for disease related autoantibodies. The objective of this study was to characterize anti-sulfatide antibodies and compare antibodies from GBS and MS patients with fetal antibodies. Our hypothesis is that some B cells producing disease-associated autoantibodies are derived from or related to B cells of the fetal repertoire. Here we report that reactivity of plasma IgM against sulfatide was elevated in twelve MS patients compared with twelve normal subjects. This result implies that anti-sulfatide antibodies are disease-related. A total of sixteen human B lymphocyte clones producing anti-sulfatide autoantibodies were isolated from MS patients, GBS patients and a human fetus. Seven of the clones were from three MS patients, four of the clones were from three GBS patients and five were from the spleen of a twenty-week human fetus. Sequences have been obtained for the heavy and light chain variable regions (VDJ and VJ regions) of all of the anti-sulfatide immunoglobulins. Seven of the sixteen antibodies used VH3 for the variable region gene of the heavy chain consistent with the rate of VH3 usage in randomly selected B cells. Somatic mutations were significantly more frequent in the patient antibodies than in the fetus and somatic mutations in CDR's (Complementarity Determining Region) were significantly more frequent than in framework regions. No significant difference was found between patients and fetus in length of VH CDRIII. However, it is reported that antibodies from randomly selected normal adult B cells have longer CDRIII lengths than those of the fetus (Sanz I, 1991 Journal of Immunology Sep 1;147(5):1720-9). Our results are consistent with derivation of the precursors of B cells producing these autoantibodies from B cells related to those of the fetal repertoire. These findings are consistent with a model in which quiescent B cells from clones produced early in development undergo proliferation in dysregulated disease states, accumulating somatic mutations and increasing in reactivity toward self-antigens. ^ Epitope mapping and molecular modeling were done to elucidate the relationships between antibody structure and binding characteristics. The autoantibodies were tested for binding activity to three different antigens: sulfatide, galactoceramide and ceramide. Molecular modeling suggests that antibodies with positive charge surrounded by or adjacent to hydrophobic groups in the binding pocket bind to the head of sulfatide via the sulfate group through electrostatic interactions. However, the antibodies with hydrophobic groups separated from positive charges appear to bind to the hydrophobic tail of sulfatide. This observation was supported by a study of the effect of NaCl concentration on antigen binding. The result suggested that electrostatic interactions played a major role in sulfate group binding and that hydrophobic interactions were of greater importance for binding to the ceramide group. Our three-dimensional structure data indicated that epitope specificity of these antibodies is more predictable at the level of tertiary than primary structure and suggested positive selection based on structure occurred in the. formation of those autoantibodies. ^

The anti-apartheid movement in Japan : an overview

Anti-apartheid movements outside South Africa have been recently becoming a popular research topic as an indispensable part of the history of the liberation struggle against apartheid, as well as from the “global civil society” point of view, i.e. anti-apartheid movements as one of the earliest examples of transnational social movements with the aim of realization of global justice. The Japanese movement, however, has attracted little attention so far, despite its history of nearly half century. The Japanese movement’s characteristic foci and style, reflecting the unique position of Japan as a non-white nation with strong trade relations with white-dominated South Africa, certainly deserves detailed study. This paper is an attempt to fill the gap by outlining the history of the anti-apartheid movement in Japan.

The framing discourses of 'Honorary white' in the anti-apartheid movement in Japan

International and transnational solidarity is being increasingly recognized as an indispensable part in the recent historiography on the liberation struggle in Southern Africa. Yet the literature has mostly focused on anti-apartheid movements in the West, and anti-apartheid movements in Asia have attracted little attention. Focusing on the Japanese citizens' movement (shimin undo) against apartheid, which loosely coalesced into the Japan Anti-Apartheid Committee (JAAC), this paper looks into how the issue of 'honorary white' was brought into the early period of the anti-apartheid movement in Japan, and how the framing discourses of the movement was developed around the issue.

Los agentes de la edificación desde el punto de vista de la Gestión Integral de Proyectos: diferencias y semejanzas entre la Legislación Española y los Estándares Internacionales = Expert agents in the Global Development of a building project: differences and similarities between Spanish and International contexts.

Desde los años 60, crece en Europa y Estados Unidos la preocupación y la necesidad de mejorar los procesos de gerencia de los proyectos de construcción al volverse estos más complejos. Esto ha llevado a la continua aparición de nuevos profesionales desde la fecha citada hasta nuestros días. De ahí la complejidad de conocer las cualidades de cada uno de ellos, así como las funciones a realizar o la formación que deben tener para poder desarrollar el puesto de trabajo según el papel que desempeñan para cada actividad. Muchos agentes son los que pueden intervenir en la edificación, muchas son las funciones que llevan a cabo estos agentes, muchas son las habilidades que se necesitan para realizar estas misiones, y una buena gestión de la edificación es la que hay que desarrollar para lograr el gran éxito. El presente trabajo fin de máster, dirigido a arquitectos, arquitectos técnicos, ingenieros, abogados, economistas y todos los profesionales del sector inmobiliario y de la construcción, trata de resolver todas aquellas dudas sobre los diferentes sujetos que estarán presentes desde la definición del proyecto en la fase inicial hasta el final de la obra, pasando por las fases de pre-construcción, construcción y post-construcción. (ENGLISH VERSION) Since the 1960s, most construction projects have become more and more complex, and new concerns and necessities related to the management of a project have been on the rise in Europe and in the United States. Thence, the need for more specialized professionals in the field has become a common fact, as well as the inclusion of new curricular subjects in most building engineering studies. There are different agents that play a relevant role in a building project; some of them are expected to perform a highly specialized set of functions that require specific management skills for the work to be successful. This research work—aimed mainly at engineers, quantity surveyors, lawyers, economists, real estate and construction professionals—shows the major implications of the building construction process including both pre-tender/construction and post-tender/construction stages as far as the main expert agents are involved.

Antibodies to ribosomal P proteins of Trypanosoma cruzi in Chagas disease possess functional autoreactivity with heart tissue and differ from anti-P autoantibodies in lupus

Anti-P antibodies present in sera from patients with chronic Chagas heart disease (cChHD) recognize peptide R13, EEEDDDMGFGLFD, which encompasses the C-terminal region of the Trypanosoma cruzi ribosomal P1 and P2 proteins. This peptide shares homology with the C-terminal region (peptide H13 EESDDDMGFGLFD) of the human ribosomal P proteins, which is in turn the target of anti-P autoantibodies in systemic lupus erythematosus (SLE), and with the acidic epitope, AESDE, of the second extracellular loop of the β1-adrenergic receptor. Anti-P antibodies from chagasic patients showed a marked preference for recombinant parasite ribosomal P proteins and peptides, whereas anti-P autoantibodies from SLE reacted with human and parasite ribosomal P proteins and peptides to the same extent. A semi-quantitative estimation of the binding of cChHD anti-P antibodies to R13 and H13 using biosensor technology indicated that the average affinity constant was about 5 times higher for R13 than for H13. Competitive enzyme immunoassays demonstrated that cChHD anti-P antibodies bind to the acidic portions of peptide H13, as well as to peptide H26R, encompassing the second extracellular loop of the β1 adrenoreceptor. Anti-P antibodies isolated from cChHD patients exert a positive chronotropic effect in vitro on cardiomyocytes from neonatal rats, which resembles closely that of anti-β1 receptor antibodies isolated from the same patient. In contrast, SLE anti-P autoantibodies have no functional effect. Our results suggest that the adrenergic-stimulating activity of anti-P antibodies may be implicated in the induction of functional myocardial impairments observed in cChHD.

Meta-analysis of short term low dose prednisolone versus placebo and non-steroidal anti-inflammatory drugs in rheumatoid arthritis

Objective: To determine whether short term, oral low dose prednisolone (⩽15 mg daily) is superior to placebo and non-steroidal anti-inflammatory drugs in patients with rheumatoid arthritis.

Ubiquitin-protein ligase activity of X-linked inhibitor of apoptosis protein promotes proteasomal degradation of caspase-3 and enhances its anti-apoptotic effect in Fas-induced cell death

The inhibitor of apoptosis (IAP) family of anti-apoptotic proteins regulate programmed cell death and/or apoptosis. One such protein, X-linked IAP (XIAP), inhibits the activity of the cell death proteases, caspase-3, -7, and -9. In this study, using constitutively active mutants of caspase-3, we found that XIAP promotes the degradation of active-form caspase-3, but not procaspase-3, in living cells. The XIAP mutants, which cannot interact with caspase-3, had little or no activity of promoting the degradation of caspase-3. RING finger mutants of XIAP also could not promote the degradation of caspase-3. A proteasome inhibitor suppressed the degradation of caspase-3 by XIAP, suggesting the involvement of a ubiquitin-proteasome pathway in the degradation. An in vitro ubiquitination assay revealed that XIAP acts as a ubiquitin-protein ligase for caspase-3. Caspase-3 was ubiquitinated in the presence of XIAP in living cells. Both the association of XIAP with caspase-3 and the RING finger domain of XIAP were essential for ubiquitination. Finally, the RING finger mutants of XIAP were less effective than wild-type XIAP at preventing apoptosis induced by overexpression of either active-form caspase-3 or Fas. These results demonstrate that the ubiquitin-protein ligase activity of XIAP promotes the degradation of caspase-3, which enhances its anti-apoptotic effect.