Animal model: immunologic model of inflammatory bowel disease.
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Following observations that the intracerebral injection into rats of antiserum to brain gangliosides resulted in recurrent epileptiform activity and that seizure activity was not seen if antibodies were removed by absorption of the antiserum with pure GM1 ganglioside, a study was undertaken to establish characteristics of the immunological agents used to produce this model of epilepsy. It was determined that the potencies (antibody titers with GM1 ganglioside) of antiganglioside sera can be correlated with the intensities of epileptiform activity they induce; that immunoglobulin fractions from antiganglioside sera are even more effective biologically than the antisera; and that antibodies to GM1 ganglioside purified by affinity chromatography can also induce recurrent epileptiform discharges but are not as effective as either native antiserum or immunoglobulin fractions.
Carcinoma of the cervix uteri is one of the most important tumors in women. The tumor induces an immunological defense reaction against itself in the tumor host. The round cell infiltrate at the tumor invasion line, which predominantly consists of small lymphocytes is the morphological equivalent of this interrelationship. In the lymph-nodes of the drainage area of the tumor certain patterns of reaction can be differentiated, which may be interpreted as humoral or cellular immune reactions. Cellular immune reactions in lymph-nodes of patients operated according to the method of Wertheim-Meigs were correlated with a better prognosis of the tumor disease. The hypothesis of an involvement of the HSV-type II in the genesis of the cervical carcinoma is supported by the increased incidence of antibodies against the virus. Therewith, relations between the stage of disease and the age of the patient were found as a possible basis for the virus hypothesis and the immune reaction to the tumor associated antigens an altered genetic situation may be presumed. Typing in the HLA-system demonstrates an accumulation of the frequency of the antigen B12 in patients with carcinoma of the cervix. These investigations may lead to a differentiated outlook with regard to the detection of risk groups and therapeutical consequences for cervical cancer.
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Several gold salts were compared in kaolin-induced rat paw oedema, u.v. erythema in guinea pigs, delayed type hypersensitivity and humoral immunity in mice, and adjuvant-induced arthritis in the rat. In the latter the additional parameters of serum gold and copper levels and lysosomal enzyme activity were determined. In addition, the in vitro inhibition of several lysosomal enzymes derived from mouse macrophages was studied. The gold compounds examined were aurothiomalate, aurothioglucose, triethylphosphine gold chloride (SK & F 36914) and its glucopyranoside derivative (SK & F D-39162), triphenylphosphine gold chloride and sodium gold chloride dihydrate. SK & F 36914 and SK & F D-39162 has significant activity after oral dosage upon paw kaolin and u.v. erythema in rats and guinea pigs, respectively. Gastric swelling also occurred. In Wistar rats, adjuvant arthritis was little affected by the gold salts but in the Lewis rats there was suppression. In both strains there was less elevation in serum copper levels with treatment by SK & F 36914 and SK & F D-39162, but not by aurothiomalate. None of the compounds had any measurable effect on delayed hypersensitivity or humoral antibody levels in mice. The in vitro activities of cathepsin B1 and cathepsin D were inhibited by all the gold compounds. Reactivity of gold compounds with glutathione and cysteine in vitro was dependent on compound solubility and the nature of the gold ligand. Considerable differences exist between the profiles of activity for the different gold salts evaluated. These observations indicate that some gold salts do possess anti-inflammatory activity with a potency similar to that of indomethacin.
Antibodies to GM1 ganglioside injected into the sensorimotor cortex of the rat induce recurrent epileptiform activity. We now find that the divalent F(ab')2 and monovalent Fab' fragments derived from antiganglioside IgG molecules are able to induce epileptiform seizures. This result supports the view that the binding of antibodies to ganglioside receptors in the synaptic membrane is sufficient in itself to initiate changes in membrane processes which lead to epileptiform spiking. These changes do not appear to be dependent on linking of ganglioside receptors or on the presence of serum factors such as complement.
A protein of 75 kDa is produced in large quantities by the human malarial parasite Plasmodium falciparum and is present on the surface of the merozoite, whose function is to infect erythrocytes. Based on nucleotide sequence coding for 40% of this protein, two nonoverlapping model peptides 13 and 19 residues long were synthesized, coupled to a keyhole limpet hemocyanin carrier, and used to immunize rabbits. Although both antisera had high titers of anti-peptide antibodies, only that raised against the 13-residue peptide showed good reactivity against the original protein. Although the 19-mer adopted the helical secondary structure predicted for the corresponding protein region, antisera against this peptide reacted with the native protein weakly or not at all. Concluding that the poor anti-protein reactivity was due to modification of lysine-containing epitopes by glutaraldehyde conjugation, we used a carrier-free 28-residue peptide presented as a 56-residue disulfide-bonded dimer to model the same region. This peptide, in contrast to the conjugated 19-mer, stimulated the production of IgG antibodies that reacted at high dilution with the authentic protein in immunoblots, ELISA, and radioimmunoprecipitation assays. These data indicate that large carrier-free peptides may be successfully used as immunogens. In addition, our results show that this strategy may greatly improve the ability of conjugation-sensitive peptides to stimulate antibodies reactive with the original protein and therefore has substantial practical application.
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Studies have shown that the parent myelin basic protein (MBP) is a more potent antigen than its disease-inducing fragments. Based on equimolar ratios, 10-15 times more peptide is required to induce experimental allergic encephalomyelitis (EAE) with the same severity as that induced by the intact MBP. In this report, we show that 2 epitopes are required for EAE in Lewis rats; that which induces T cell-mediated immunity requires the expression of a B cell epitope for the development of full spectrum of clinical and histopathological signs of disease. Thus, the development of disease may be related to the magnitude of the humoral and cellular responses to particular B and T cell epitopes. Whether more than 1 epitope, over 30 of which have been located in the MBP, contribute to the development of MBP-induced disease is not clear; but what is clear is that the EAE-inducing peptide sequence, unlike the MBP, is restricted in terms of the number of recognizable epitopes.
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