Immunoprophylaxis against Leishmania infections with a semi-purified antigen.
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Biomedical subjects
Publications and source records attributed to D Frommel.
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Five out of seven American woodchucks inoculated with woodchuck hepatitis virus developed antigenemia after 2 to 13 weeks followed by an antibody response. One animal became a carrier, and another animal exhibited a primary antibody response. Clinical disease was not obvious and aminotransferase elevation could not be demonstrated. Liver biopsy showed mononuclear portal infiltration and little parenchymal cell necrosis.
Merozoites obtained from cutaneous cultures of Plasmodium falciparum were used as antigen for an in vitro lymphocyte assay. Antigen specific proliferative responses were observed with lymphocytes from individuals with long-standing immunity to P. falciparum. Donors whose last P. falciparum challenge occurred within the year preceding the assay exhibited lymphocyte responses significantly higher than those from donors whose infection was more remote. This suggests that a lymphocyte dependent assay may relate to the protective status of the donor.
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A movement opposing the nuclear arms race asked for medical surveillance of four people intending to go without food for an unlimited period. The course of fasting was uneventful until day 28-35, when weight loss reached 18%. In one subject fasting was ended on day 38 owing to development of Wernicke's encephalopathy; the others agreed to suspend their fast by day 40. The presence of physicians, offered under defined conditions, may have contributed to the timely cessation of this protest.
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The natural history of infection with woodchuck hepatitis virus (WHV) has been studied in a colony of 38 Marmota monax. Besides serologic assessment for WHV markers, light-microscopic findings of 61 liver biopsies were correlated with the results of immunofluorescence analysis for nucleocapsid (WHcAg) and surface (WHsAg) antigens. Twenty-four chronic WHsAg carriers all featured signs of continuous viral replication. Two major immunomorphologic patterns were observed in their livers: 1) portal hepatitis in which WHcAg accumulated in the cytoplasm and WHsAg was associated with the hepatocyte membrane and 2) periportal hepatitis in which WHcAg shifted toward nuclear localization and WHsAg became mostly intracytoplasmic. Progression from portal to periportal hepatitis, observed in 7 woodchucks, appeared to be induced by a partial recovery of specific immune reactivity to WHV, insufficient, however, to interrupt WHV replication. Deposits of WHsAg and immunoglobulins were present in the kidney and spleen of animals with severe hepatitis.
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Antibody against liver membrane (LMA) was measured using suspensions of rabbit hepatocytes and FITC-conjugated F(ab')2 fragments of affinity-purified goat anti-human IgG. The sera of 43 children with chronic liver disease were examined. Significant titers of LMA were observed for all patients with untreated HBV-negative chronic active hepatitis (CAH). Follow-up studies during immunosuppressive therapy showed that the decrease in LMA titers was delayed as compared to that of non-organ-specific antibodies, and did not correlate with clinical, biochemical, and histological parameters. The detection of LMA is useful in the diagnosis of the CAH subtype which may benefit from immunosuppressive therapy. However, it is of no assistance in the clinical management of autoimmune CAH, since it failed to predict possible relapse after withdrawal of treatment. A pathogenic role for LMA remains thus questionable.
Cultured murine Kupffer cells were tested for their ability to bind TNP-sensitized erythrocytes coated with IgA myeloma proteins (MOPC 315 & 460) which have high affinity for TNP ligands, and to ingest TNP-enzyme-IgA soluble immune complexes. In these experimental conditions, 6-18% of Kupffer cells were found to express surface binding sites for IgA, a feature they share with lymphocytes and granulocytes. This functional property, also displayed by circulating monocytes, is thus maintained in liver-residing macrophages, and may contribute to the regulation of immune response to gut-derived antigens.
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Two non-haemophilic elderly patients who had developed autoantibodies to factor VIII were studied over a period of 9 months to 5 years. Sequential measurements of antibody to factor VIII (anti-VII:C), factor VIII coagulant activity (VIII:C), factor VIII coagulant antigen (VIII:CAg), factor VIII-related antigen (VIIIR:Ag), and factor VIII ristocetin cofactor (VIII:WF) were performed. Before treatment, low VIII:C, normal or increased VIII:CAg and high VIIIR:Ag levels were found and were indicative of the presence of circulating immune complexes. Immunosuppressive therapy induced progressive correction of VIII:C and VIIIR:Ag values. High levels of VIII:CAg subsided in the patient who relapsed. It is suggested that antibodies to factor VIII bind and remove VIII:C from the circulation thereby inducing an increased synthesis of VIII:CAg which may be associated with an augmented release or production of VIIIR:Ag.
Possible interrelations between the immune response factor VIII and the major histocompatibility system were investigated in 57 multi-transfused hemophilic brothers belonging to 26 families. Linkage appears very unlikely although formal proof of independence cannot be offered. The HLA system, therefore, does not provide markers predictive for the development of antibodies to factor VIII in severe hemophilia A.
Factor VIII complex and its interaction with antibodies to factor VIII have been studied in 17 non-haemophilic patients with factor VIII inhibitor. Low VIII:C and high VIIIR:Ag levels were found in all patients. VIII:WF levels were 50% of those of VIIIR:Ag, possibly related to an increase of poorly aggregated and electrophoretically fast moving VIIIR:Ag oligomers. Antibody function has been characterized by kinetics of VIII:C inactivation, saturability by normal plasma and the slope of the affinity curve. Two major patterns were observed: 1) Antibodies from 6 patients behaved similarly to those from haemophiliacs by showing second order inhibition kinetics, easy saturability and steep affinity slope (greater than 1). 2) Antibodies from other patients, usually with lower titres, inactivated VIII:C according to complex order kinetics, were not saturable, and had a less steep affinity slope (less than 0.7). In native plasma, or after mixing with factor VIII concentrate, antibodies of the second group did not form immune complexes with the whole factor VIII molecular complex. However, dissociation procedures did release some antibodies from apparently low molecular weight complexes formed in vivo or in vitro. For appropriate management of non-haemophilic patients with factor VIII inhibitor, it is important to determine the functional properties of their antibodies to factor VIII.
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The liver microsomal delta 9 and delta 6 desaturase activities have been studied in rats with carbon tetrachloride-induced hepatitis. Immediately after poisoning, significant decreases were observed for both types of desaturase activity. However, recovery kinetics were slower for the delta 6 desaturase than for the delta 9 desaturase. The activities of NADH-ferricyanide and NADH-cytochrome C reductases, proteins involved in the electron transfers associated with microsomal desaturation, were also measured. There was a fall in both activities after poisoning, but this decrease was less than that of the desaturase activities.
Liver-membrane auto-antibodies (LMA) were searched for in children with histologically proven chronic active hepatitis. LMA were found in the serum of all 20 patients under study. In the 6 cases associated with hepatitis B virus, LMA were the sole marker for auto-immunity; in 11 cases, negative for HBsAg, other anti-tissue antibodies, smooth muscle or endoplasmic reticulum antibody, coexisted. Neither prior to therapy nor during treatment with prednisone and azathioprine was there any correlation between titres of LMA and those of other auto-antibodies nor with the assessment of histological activity. Although a reliable diagnostic marker, LMA, as revealed by using heterologous hepatocytes, appear to convey limited values as a prognostic marker of chronic active hepatitis in children.