Differential effects of sex hormones on autoantibody production and proteinuria in chronic graft-versus-host disease-induced experimental lupus nephritis

In patients with systemic lupus erythematosus, the female-to-male ratio is as high as 10:1. Sex hormones are thought to play a role in this difference in susceptibility. In a previous study, we demonstrated a high susceptibility of female mice to the development of glomerulonephritis after induction of chronic graft-versus-host disease (GVHD), compared with male mice. In order to unravel further this gender-related difference (C57Bl/10*DBA/2)F¹ hybrid mice were either castrated or ovariectomized and treated with 17β-ethinyloestradiol or testosterone-decanoate preceding the induction of chronic GVHD. Testosterone-decanoate reduced significantly the development of albuminuria in females. In contrast, proteinuria of 17β-ethinyloestradiol-treated female mice was in the same range as that of sham-operated mice. Autoantibody levels against glomerular basement membrane, renal tubular epithelium, dsDNA and ssDNA, as determined by ELISA, were higher in 17β-ethinyloestradiol-treated female mice than in all other groups. Immunofluorescence studies showed the presence of immunoglobulin and complement deposits in glomeruli of all animals, without significant differences between the experimental groups. Our findings confirm earlier observations, in that testosterone-decanoate is shown to be an inhibitory compound, whereas 17β-ethinyloestradiol has stimulating properties in autoimmunity. Moreover, our results show for the first time differential hormonal effects on autoantibody levels and proteinuria in experimental lupus nephritis.     

Secretion of γ-Interferon at the Cellular Level

Using a haemolytic plaque assay for gamma-interferon (IFN-gamma) secretion we found that in vitro Epstein-Barr virus (EBV) exposure of peripheral blood mononuclear cells from EBV immune individuals led to IFN-gamma secretion, which was apparent within 6 h after virus contact and peaked 12-24 h after induction. Live, ultraviolet-light-irradiated and heat-inactivated virions all caused IFN-gamma secretion. In contrast, blood mononuclear cells from EBV non-immune adults or neonates could not be activated to IFN-gamma production by EBV.     

Analysis of the Expression of I-Ak-like Antigens in Murine Fetal and Adult Tissues with the Monoclonal Antibody 10–2.16

The expression of I-Ak antigens in normal C3H/FeJ adult and 15-day embryonic mice has been investigated by indirect immunofluorescence staining of tissue cryostat sections with the anti I-Ak antigen monoclonal antibody 10-2.16. In adult mice I-Ak antigens were expressed in Langerhans-like cells in the skin, epithelium of the gastrointestinal tract, endometrium, thymic reticuloepithelial cells, and several capillary endothelia. On the other hand, these antigens were not detected in Kupffer cells, alveolar macrophages, brain or mammary gland. In 15-day-old embryos the expression of Ia-like antigens was restricted to thymic reticuloepithelial cells, isolated spleen cells, and capillaries of the gastrointestinal tract.     

Osteosarcomatosis

A review of the 690 cases of osteosarcoma in the radiographic file of the Armed Forces Institute of Pathology revealed 29 cases of "osteosarcomatosis" (multiple skeletal sites of osteosarcoma). Fifteen of these patients were 18 years old and under and manifested rapidly appearing, usually symmetric, sclerotic metaphyseal lesions. The remaining 14 patients were more than 18 years old and had fewer, asymmetric sclerotic lesions. In most patients (28 of 29), a radiographically dominant skeletal tumor was seen. Pulmonary metastases occurred in the majority of patients and were detected at the same time as the bone lesions. These 29 patients were studied with regard to demographic data and skeletal distribution and radiographic appearance of their lesions. As a result of the findings, a metastatic origin from a primary dominant osteosarcoma is favored over a multifocal origin as the basis for osteosarcomatosis. Osteosarcomatosis is more commonly encountered in the mature skeleton than has been previously recognized.     

MODULATION OF ALCOHOL PREFERENCE BY NMDA ANTAGONISTS IN MALE RATS

Chronic alcoholization by alcohol inhalation was used to studythe properties of magnesium, a non-competitive NMDA receptorantagonist, and CGP 39551, a competitive NMDA receptor antagonist,on behavioural dependence as estimated by the free-choice paradigm[alcohol 10% (v/v) vs. water], on the hypermotility after alcoholwithdrawal, and finally on the cortical vascularization. Thefirst experimental group received the drugs per os during thewhole alcoholization period. Magnesium (20 mg/kg/day) decreasedthe alcohol dependence while CGP 39551 (5 and 10 mg/kg/day)increased, in a dose-dependent manner, the dependence to alcohol.A second group of animals received the same drugs at the samedosages, not simultaneously during chronic alcoholization, butimmediately after alcoholization in one shot i.p. injection.In this case, rats receiving 5 mg/kg CGP 39551 never showedany dependence towards alcohol, while 10 mg/kg CGP 39551 or20 mg/kg magnesium prolonged the number of days of alcohol dependence.These results thus indicate the close interaction between NMDAreceptor function and dependence for alcohol. Magnesium hadno effects on hypermotility, while CGP 39551-treated animalspresented a decrease in the hypermotility observed after alcoholwithdrawal. Neither drug affected the hypervasculanzation accompanyingthe chronic alcoholization.     

LYME PERICARDITIS LEADING TO TAMPONADE

We report the case of a 62-yr-old man who presented with Lymepericarditis leading to cardiac tamponade shortly followed byan arthritis. IgM and IgG antibodies to Borrelia burgdorferiwere demonstrated in serum by indirect immunofluorescence. Borreliaburgdorferi was demonstrated and identified in pericardial fluidby indirect immunofluorescence using serum from a patient withproven Lyme disease and by a monoclonal antibody immuno-goldsilver stain. Spirochetes were also found in synovial biopsiesusing a silver stain. The tamponade was treated with pericardiocentesis;the arthritis was treated with intravenous ceftriaxone (2 gonce daily) for 14 days. The patient recovered completely withindays of commencing treatment. This case report demonstratesthat borrelial infection may lead to pericarditis and cardiactamponade. KEY WORDS: Borrelia burgdorferi infection, Arthritis, Pericarditis, Tamponade