Studies on immunostimulating derivatives: synthesis of some pyrrolo[1,2-c]pyrimidines.

In a search for potential immunomodulating agents novel pyrrolo[1,2-c]pyrimidines were synthesized and their structures elucidated by spectroscopic means. Unfortunately, most of them were cytotoxic and devoid of effects on T lymphocyte lymphoblastic transformation. Furthermore, they were inactive in the locomotor activity test in mice.

[IgA and its different molecular forms in the mesenteric, portal and peripheral venous blood in man]. / L'IgA et ses différentes formes moléculaires dans le sang veineux mésentérique, portal et périphérique chez l'homme.

The aim of this study was to assess the role of mesenteric blood in polymeric IgA (p-IgA) and IgA2-transport from the intestinal mucosa into plasma and the role of the liver in the clearance of these molecular forms of IgA. The concentrations of IgA, p-IgA and IgA2 were measured in mesenteric, splenic, portal, and hepatic veins of 7 control subjects without liver disease and in portal and peripheral veins of 4 patients with alcoholic cirrhosis. In control subjects, the concentration of the different molecular forms of IgA were not significantly different in mesenteric and in splenic vein. No significant decrease of IgA concentrations was observed in hepatic vein, as compared with portal vein. In cirrhotic patients IgA concentrations were significantly higher than in control subjects, but concentrations of IgA, p-IgA and IgA2 were not different in portal and peripheral blood. These results show that mesenteric vein is not a major way for p-IgA and IgA2 from the gut lamina propria to plasma, and suggest that the origin of a significant part of these molecular forms of IgA could be peripheral lymph-nodes more than gut-associated-lymphoid-tissue. The absence of significant clearance of p-IgA by the liver in normal subjects suggests that abnormalities of hepato-biliary transport of p-IgA is not responsible for the increased IgA levels observed in cirrhotic patients.

Guillain-Barré syndrome following danazol and corticosteroid therapy for hereditary angioedema.

A case of hereditary angioedema secondary to C1 esterase inhibitor deficiency associated with lupus-like nephritis is reported. The patient was initially treated with both corticosteroids and danazol and subsequently had Guillain-Barré syndrome together with appearance of circulating immune complexes and an increase in total complement and C1q, C3, C4, B, and C1 esterase inhibitor levels. Guillain-Barré syndrome might be secondary to danazol therapy since this drug could increase both circulating immune complex production and complement synthesis, thereby providing additional substrate for the underlying immune complex disease. Normalization of complement might therefore be hazardous in lupus with underlying complement deficiency states.

[Acquired C1 esterase inhibitor deficiency and lymphoproliferative syndromes]. / Déficit acquis en inhibiteur de la C1 estérase et syndrome lymphoprolifératif.

About 20 cases of acquired C1 esterase inhibitor deficiency have been reported in association with malignant lymphomas. We describe 3 such patients. The 3 patients studied were asymptomatic and had low C1q level. Danazol administration resulted in an increase of C1 esterase inhibitor in 2 patients. The complement activation in acquired C1 esterase inhibitor deficiency could be explained by interaction with pathological cells of the spleen, the blood or the bone-marrow. The mechanism of decrease of C1 INH is discussed.

[Hereditary deficiency of C1 esterase inhibitor. Lupus and glomerulonephritis]. / Déficit héréditaire en inhibiteur de la C1 estérase. Lupus et glomérulonéphrite.

Congenital deficit of the inhibitor of C1 esterase (C1 INH) usually presents by oedema of the lower limbs, abdomen and glottis (sometimes lethal), which explains its clinical denomination of angioneurotic oedema. The association of this condition with disseminated lupus erythematosis has been reported in 4 cases and with discoid lupus in 4 cases. Antinuclear factors were found in all these cases but there were only two documented cases of nephropathy (one diffuse proliferative glomerulonephritis and one local glomerulonephritis). The association of a deficit of C1 INH and membrano-proliferative glomerulonephritis has only been reported in 2 cases (one lobular glomerulonephritis and one glomerulonephritis with dense basal membrane deposits). Our case had C1 INH deficiency and proliferative lupic glomerulonephritis in the absence of other clinical and immunological signs of DLE. Nephropathy was not looked for in 9 cases of association of C1 INH deficiency and C3-shearing autoantibody (C3 NEF). A common genetic mechanism for these associations seems very improbable. The aptitude of patients with C1 INH deficiency to synthesise autoantibodies under the influence of infections factors, for example, could explain the higher incidence of lupus and glomerulopathies in these patients.

[Immune complex nephropathy and hereditary deficiency of C1 esterase inhibitor (author's transl)]. / Néphropathie à complexes immuns et déficit héréditaire en inhibiteur de la C1 estérase.

Deficiency of C1 esterase inhibitor (C1-INH) was demonstrated in 7 of 22 subjects belonging to the same French family. Immune complex glomerulonephritis without lupic symptoms was discovered in one of the C1-INH deficient subjects, and in a girl of the same family the same deficiency was associated with an insulin-dependent diabetes of sudden onset. The pathophysiological consequences of complement deficiency resulting from the lack of C1 esterase inhibitor are discussed.

[Culture of hepatitis virus B]. / Culture du virus B de l'hepatite

For the last 25 years, numerous attempts have been made to isolate the HBV agent responsible for hepatitis B by means of cultures 'in vitro'. We have undertaken longterm cultures of children's hepatic tissue (C.H.), conjunctive tissue (human adult H.A.F. and human embryonic fibroblasts H.E.F.) and KB cells; these were put in the presence of 7 sera HB + rich in Dane particles. These cells were trypsinized twice a week for almost 3 months and did not present any cytopathogenic effects. Electromicroscopy revealed, 15 days after infection, the presence of icosahedral particles (25 to 27 nm in diameter), free or in dense clusters, but more often empty (20 nm in diameter). These structures seemed to be made up of an assembly of capsomers approximately 5 nm in diameter, joined together in fours to form a ridge. Older cultures revealed clusters of icosahedrons some of which degenerated spontaneously; others were surrounded by proteinic structure having a fringed aspect. Certain rare particles of 35 to 45 nm in diameter are similar to full Dane particles. EID immunological results were positive in the case of sera of patients convalescent from hepatitis B, containing anti-HBc antibodies, on C.H. cells the 27th and 40th days, and negative with anti-HBs antibodies. By immunofluorescence we observed 12 to 20 days after infection of the cells, a clear fluorescence at first nuclear, then essentially cytoplasmic, by means of fluorescent anti-HBc sera of human or animal origin. With the fluorescent anti-HBs antibodies, the reaction is weak and solely cytoplasmic although in DRI, with H.E.F. and KB cells, we obtained from time to time weakly positive results in HBs. The relations between the morphological structures and the immunological results observed are discussed.