New Zealand white rabbits immunized with RNA-complexed total histones develop an autoimmune-like response.

The antibody response of rabbits immunized with a total histone mixture containing randomly coiled H1/H5, H2A, H2B, H3 and H4 devoid of DNA was investigated in direct and competitive ELISA. The antisera were tested with isolated histones and chromatin and with a series of overlapping synthetic peptides covering the entire sequences of the four core histones and two peptides of H1. It was found that the New Zealand (NZ) white rabbits immunized with the total histone (TH) mixture complexed with RNA produced IgG antibodies reacting with histones and with a number of histone peptides but not with chromatin. The antisera also contained IgG antibodies which bound components that correspond to common target antigens in autoimmune diseases such as native dsDNA, peptides of Sm-D antigen, ubiquitin, branched peptides of ubiquitinated H2A and poly(ADP-ribose). By competition experiments, it was shown that these antibodies corresponded to non-crossreacting antibody populations. New Zealand rabbits immunized with TH in the absence of RNA or random outbred rabbits immunized with the RNA-complexed histone fraction produced antibodies reacting with histone, chromatin and very few histone peptides, while no activity with non-related antigens was observed. The pattern of reactivity of antisera raised in NZ rabbits with RNA-complexed TH was found to be very similar to that observed in sera of patients with systemic lupus erythematosus while, in contrast, the antibody response was very different in NZ or outbred rabbits immunized with various native nuclear particles and with individual histones. Altered nucleosome particles rather than native nucleosomes may represent the antigenic stimulus giving rise to autoantibodies.     

Characterization of a monoclonal anti-Bw4 antibody (Tü109): Evidence for similar epitopes on the Bw4 and Bw6 antigens

The production and serologic, as well as immunochemical properties of a cytotoxic murine IgG monoclonal antibody (Tü109) that precipitates HLA-class I molecules, are described. In the microcytotoxicity assay Tü109 supernatant was demonstrated on a panel of 424 HLA-ABC, -DR, -DQ, -MT typed normal Caucasian blood donors to define an epitope on HLA-B locus molecules in great association with the supertypic specificity Bw4. Reactivity of supernatant showed MHC linked inheritance of the Tü109 determinant and discriminated the HLA-Bw4/Bw6 associated HLA-B locus split antigens. Weak or lack of binding on lymphocytes from some HLA-Bw4 heterozygous individuals, particularly typing for HLA-Bw44, appeared to be due to qualitative and/or quantitative variations of HLA-B locus molecules on the cell surface. With Tü109 ascites fluid, however, extra-reactivity on all HLA-Bw6⁺ cells was demonstrated. Preferential binding of supernatant to HLA-Bw4, but reactivity of ascites fluid with HLA-Bw6⁺ molecules in addition, was furthermore confirmed by IEF analysis of antigens immunoprecipitated with Tü109 from cell lysates. Thus the antibody may help to analyze the evolutionary relationship of the diallelic specificities Bw4 and Bw6.     

Early time course of the acute phase protein response in man.

The rate at which the acute phase protein response occurred after both major and minor surgery was explored. Increases in the plasma concentration of C-reactive protein (CRP), alpha-1-acid glycoprotein (alpha 1 AG) and fibrinogen were not detected until 6-8 h after the initial incision. The peak concentration of CRP occurred at 48 h and that of fibrinogen at 96 h; alpha 1 AG concentrations rose rapidly until 48 h followed by little change until about 120 h. Although there was widespread variation in the concentrations of individual proteins in patients, severity of injury did not seem to have a significant effect on the time course of the change. Plasma cortisol concentration and the total white blood cell count (WBC) reached their peaks before the acute phase proteins, cortisol at 6 h and WBC at 12 h.     

Anatomic basis of the transgluteal approach to the hip-joint by anterior hemimyotomy of the gluteus medius

The authors present a study of the intrinsic anatomy of the gluteus medius m. and of its innervation through the caudal branch of the superior gluteal n. The existence of an intramuscular tendon in the thickness of the gluteus medius was constantly prooved in 40 muscles. The relations of the intrinsic fibrous structure of the muscle and its innervation were studied. The authors deduce from that the topography of a gluteus medius incision, with respect to a safety area towards its innervation, which leads to an exposure of the acetabulum that is satisfying and gives opportunities of a sound repair after the surgery of the hip joint through the transgluteal approach. They propose the anterior hemimyotomy of the gluteus medius m designation.

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Bases anatomiques de l'abord transglutéal de la hanche par hémimyotomie antérieure du muscle moyen fessier

Résumé Les auteurs présentent une étude de l'anatomie intrinsèque du m. moyen fessier (MF) et de son innervation par le rameau caudal du n. glutéal supérieur (NGS). 40 muscles ont été étudiés. L'existence d'une lame tendineuse dans l'épaisseur du MF a été constamment mise en évidence. Les rapports entre les éléments de l'architecture fibreuse intrinsèque du muscle et son innervation ont été étudiés. Les auteurs en déduisent la topographie d'une incision du MF respectant une zone de sécurité vis à vis de son innervation, procurant une exposition acétabulaire satisfaisante et des possibilités de réparation solide après chirurgie de l'articulation coxo-fémorale par voie d'abord transglutéale, et proposent la dénomination hémimyotomie antérieure du MF.

     

Requests for euthanasia or physician-assisted suicide from older persons who do not have a severe disease: an interview study

OBJECTIVE: To determine how often requests are made for euthanasia and physician-assisted suicide (EAS) in the absence of severe disease and how such requests are dealt with in medical practice in The Netherlands. METHOD: Retrospective interview study. Participants: 125 general practitioners (GPs), 77 nursing home physicians (NHPs), and 208 clinical specialists. RESULTS: In The Netherlands, each year approximately 400 people request EAS, because they are 'weary of life'. Thirty per cent of all physicians have at some time received an explicit request for EAS in the absence of severe disease; 3% of all physicians had granted a request for EAS in such a case. Most requests for EAS to GPs in the absence of severe disease (n = 29) were made by single people aged 80 years and over. While their problems were most frequently of a social nature, 79% had one or more non-severe illnesses. Most GPs refused the request; half of them proposed an alternative treatment, which the patient often refused. Nineteen people who did not receive any treatment persisted in their wish to die; the request for EAS from 5 out of 10 patients who received one or more types of treatment was withdrawn or became less explicit. CONCLUSIONS: Most physicians in The Netherlands refuse requests for EAS in the absence of severe disease. Most patients persist in their request. In an ageing population more research is needed to provide physicians with practical interventions to prevent suicide and to make life bearable and satisfactory for elderly people who wish to die.     

Anti-SSA/Ro52 autoantibodies blocking the cardiac 5-HT4 serotoninergic receptor could explain neonatal lupus congenital heart block

The 52-kDa SSA/Ro (Ro52) ribonucleoprotein is an antigenic target strongly associated with the autoimmune response in mothers whose children develop neonatal lupus and congenital heart block. When sera from patients with systemic lupus erythematosus were used as autoimmune controls in an enzyme immunoassay to screen for antibodies against the human serotoninergic 5-HT4-receptor, a high correlation was found between the presence of anti-Ro52 protein antibodies in such sera and antibodies reacting with a synthetic peptide, corresponding to the second extracellular loop of the human 5-HT4 receptor (amino acid residues 165-185). Homology scanning between the 5-HT4 peptide and the sequence of the Ro52 protein indicated two potential common epitopes located between residues 365 and 396 of the Ro52 protein. Cross-reactivity was found between the peptide derived from the 5-HT4 receptor, and a peptide corresponding to residues 365-382 of the Ro52 protein. Autoantibodies, affinity-purified on the 5-HT4 receptor peptide, specifically recognized both the Ro52 protein and the 5-HT4 receptor protein in immunoblots. The affinity-purified antibodies antagonized the serotonin-induced L-type Ca channel activation on human atrial cells. This effect could explain the electrophysiological abnormalities in neonatal lupus.     

Lymphohaemopoietic antigens of cultured human glomerular epithelial cells.

Glomerular visceral epithelial cells (GVEC) from normal human glomeruli were grown in tissue culture. Cell surface markers were studied by immunofluorescence microscopy using antibodies against lymphohaemopoietic differentiation antigens which are known to be present early (BA-1, OKB2, BA-2) and late (J5, anti CR1) in renal ontogenesis. Like foetal human glomerular epithelium, the cultured cells reacted with BA-1 and OKB2 (identifying an antigen expressed on B cells and polymorphonuclear leucocytes), and BA-2 (leukaemia-associated antigen), but were consistently negative for CR1 (C3b receptor); J5 which identifies the common acute lymphoblastic leukaemia antigen (CALLA) stained variably. Reactivity with antimyosin or anti factor VIII were absent. The cells produced an extracellular matrix containing laminin, type IV collagen, and fibronectin. This study supports the notion that GVEC undergo dedifferentiation as shown by the acquisition of lymphohaemopoietic differentiation antigens present early in renal ontogeny. In addition, the production of extracellular matrix constituents in vitro may be useful for the investigation of human glomerular basement membranes.