Sera from lipopolysaccharide (LPS)-injected mice exhibit complement-dependent cytotoxicity against syngeneic and autologous spleen cells.
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Animals↗
Biomedical subjects
L Hammarström
Publications and source records attributed to L Hammarström.
Polyclonal B-cell activators induce immunological response to autologous serum proteins.
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Autoantibodies↗
Multiple lesions of the lip exhibiting the "Jadassohn phenomenon". Review of the literature and report of a case.
The clinical and microscopic features of multiple, superficial lesions of the lip and adjacent mucosa in an elderly woman are reported. The lesions had been present for many years apparently without symptoms. A histologically confusing picture gave rise to diagnostic problems. Characteristic nests of basaloid cells were present at all levels of the acanthotic epithelium together with microcysts, horn pearls and squamous cell eddies. Review of the literature revealed no previous report on similar lesions of the oral mucosa and it is suggested that the lesions closely coincide with the Jadassohn type of intra-epidermal epithelioma.
Aged↗
In vitro activating properties of polyene antibiotics for murine lymphocytes.
The effect of four polyene antibiotics, Candicidin, Etruscomycin, Filipin and Pimaricin upon mouse lymphocytes was studied. Polyene antibiotics are known to form aqueous pores in the cell membranes inducing known anion or cation selective fluxes. Candicidin was capable of inducing marked DNA-synthesis and polyclonal antibody production when added to normal spleen cells. Etruscomycin and Pimaricin showed a weak inconsistent DNA synthetic stimulatory effect, whereas Filipin was found to be totally uneffective. The stimulating property of Candicidin was also demonstrated on spleen cells from nude mice whereas there was no effect on cortisone resistant thymocytes or spleen cells passed through a nylon fibre column. Thus we conclude that Candicidin is a PBA for mouse lymphocytes. We have previously reported that the two anionselective polyenes, Nystatin and Amphotericin B, are polyclonal B-cell activators for mouse lymphocytes and in this paper the possible mechanism of triggering is further discussed.
Animals↗
Polymyxins as inhibitors of polyclonal B-cell activators in murine lymphocyte cultures.
The polymyxin antibiotics polymyxin B sulfate and colistin methane sulfonate were examined for their ability to inhibit responses to the polyclonal B-cell activators (PBA) bacterial lipopolysaccharide (LPS), dextran sulfate (DS), pneumococcal polysaccharide (SIII), and purified protein derivative of tuberculin (PPD) in spleen cell cultures. Polymyxin concentrations of 1 and 10 microng/ml significantly inhibited both the deoxyribonucleic acid synthetic and polyclonal antibody responses stimulated by LPS, DS, and SIII. At these concentrations of polymyxins, responses to PPD and to the T-cell mitogens concanavalin A and phytohemagglutinin were not affected. Inhibition was not caused by a generalized lymphocyte toxicity. After dialysis of LPS-polymyxin and DS-polymyxin mixtures, the PBA preparations showed decreased mitogenic activity. Thus, the polymyxins probably interacted directly with the LPS and DS molecules. The mitogenic response to DS was more significantly inhibited than the response to a nonsulfated dextran. The cationic property of the polymyxins probably allows attachment to negatively charged groups in the mitogenically relevant parts of some but not all PBA molecules,, this attachment resulting in the loss of PBA activity.
Animals↗
Myasthenia gravis: steroid-induced effects on lymphocyte subpopulations in myasthenia gravis.
Lymphocyte subpopulations from patients with myasthenia gravis were evaluated during chronic steroid therapy. A marked lymphocytopenia (10-70%) was initially (day 3-21) noticed as well as a preferential depletion of thymus-derived cells which paralleled the clinical deterioration. Thus there was a relative increase in B cells, although their absolute number remained rather constant. These changes were reverted within 2-4 weeks in spite of continuous treatment. These findings are compatible with a release of myasthenic factors (anti-acetylcholine receptor antibodies?) during the initial steroid-induced cell damage, the long-term beneficial effects being due to loss or suppression of autoreactive helper t cells.
Adolescent↗
In vivo suppression of uterine lymphocytes during early human pregnancy.
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Female↗
Distribution of 99Tcm-labelled phosphorus compounds, 45Ca and 85Sr in diphosphonate-treated rats.
A similar distribution of 99Tcm, 45Ca and 85Sr was obtained when injected in rats as 99Tcm-labelled pyrophosphate or ethylene-1-hydroxy-1,1-diphosphonate (EHDP), 45Ca-chloride and 85Sr-choloride respectively. The highest concentrations occurred in bone and teeth. In EHDP-treated rats, isotopes were accumulated at sites of ectopic calcifications in the lung, kidney and stomach wall as well as in mineralized tissues. These results indicate that 99Tcm, when administered as 99Tcm-labelled EHDP accumulates predominatly in the inorganic rather than organic tissue components.
Animals↗
Evidence for the existence of self-reactive human B lymphocytes.
Supernatants from human tonsil cells cultured in the presence of the PBAs, LPS and F (ab)2 monomers of rabbit anti-human beta2-microglobulin were found to have a complement-dependent cytotoxic activity to tonsil cells of the same donors. A direct toxic effect of the PBAs on the target cells was excluded by controls. Therefore the most likely explanation for this finding is that human lymphocytes contain a subpopulation of self-reactive B cells which can be triggered by PBAs to release antibodies to self-antigens. The implications of this finding for the understanding of infections accompanied by auto-immune phenomena are discussed.
Antibody Formation↗
Induction of autoantibodies to red blood cells by polyclonal B-cell activators.
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Animals↗
The effect of membrane stabilizing agents on induction of the immune response. I. Effect of lymphocyte activation in mixed lymphocyte reactions.
The effect of three membrane-stabilizing agents, chlorpromazine, imipramine, and lidocain, on in vitro activation of cellular responses was studied using the one-way MLR. Cellular activation was found to be depressed by these drugs. However, the degree of suppression paralleled the decline of viable cells in the cultures. It is concluded that drug-induced inhibition of MLR was due solely to the toxicity of the compounds.
Animals↗
Spleen cells from animals tolerant to a thymus-dependent antigen can be activated by lipopolysaccharide to synthesize antibodies against the tolerogen.
Immunological tolerance was induced in adult mice by the injection of 5 mg of deaggregated hapten-protein conjugate. The tolerant state was confirmed 4-19 days later by the failure of such animals to mount an immune response against an aggregated form of the same thymus-dependent hapten-protein conjugate as well as by the inability of spleen cells from tolerant animals to respond to a thymus-independent hapten-carrier conjugate. Even though the animals were fully tolerant, their spleen cells were activated by lipopolysaccharide (LPS) in vitro to produce normal numbers of plaque-forming cells against the hapten. The finding that spleen cells from tolerant animals could be activated by LPS into synthesis of antibodies against the tolerogen indicates that tolerance to thymus-dependent antigens does not affect B cells, but presumably only T cells. It is suggested that the only stringent test for the existence of B-cell tolerance is the inability of polyclonal B-cell activators to activate antibody synthesis against the tolerogen. The findings make it unlikely that B-cell tolerance to autologous thymus-dependent antigens exists and further indicate that such antigens cannot deliver activating or tolerogenic signals to B cells, although they are competent to combine with and block the Ig receptors.
Animals↗
Association between mitogenicity and immunogenicity of 4-hydroxy-3,5-dinitrophenacetyl-lipopolysaccharide, a T-independent antigen.
Polymyxin B, which is a basic polypeptide produced by various strains of Bacillus Polymyxa, has previously been shown to prevent the lethal effect of LPS and to neutralize the Schwartzmann reaction. In this study we have investigated the interactions between polymyxin B and lipopolysaccharide (LPS) and hapten LPS conjugates. Polymyxin B was found to suppress mitogenicity of LPS and also to inhibit immunogenicity of the hapten conjugate 4-hydroxy-3,5-dinitrophenacetyl (NNP)-LPS. Inhibition was not due to interference with the expression of NNP determinants nor to cross-reactivity between PB and the hapten. Since mitogenicity and immunogenicity decreased in parallel, we conclude that B-cell activation in specific thymus independent responses does not take place in the absence of a nonspecific (non-Ig-mediated) signal.
Animals↗
Mitogenic properties of polyene antibiotics for murine B cells.
Two polyene antibiotics, nystatin and amphotericin B, were found to be mitogenic for mouse spleen cells as measured by induction of DNA synthesis and polyclonal antibody production. This effect was demonstrated on spleen cells from nude mice and anti-theta-treated spleen cells from normal mice. No effect was found on cortisone-resistant thymocytes or on spleen cells treated with anti-mouse bone marrow-derived lymphocyte antigen antiserum. Nor was there any effect on spleen cells passed through a nylon fiber column. Thus we conclude that nystatin and amphotericin B are murine B-cell mitogens.
Amphotericin B↗
HL-A8 and LD-8a in patients with myasthenia gravis.
The frequency of HL-A8 in myasthenia gravis is markedly increased in women (60-80%) but not in men. The MLC determinant, LD-8a, is frequently associated with HL-A8. Of the 37 female MS patients, 15 were LD-8a positive (41%), whereas of the males only one of seven was LD-8a positive. The frequency of HL-A8 was 68% in women and 29% in men with the disease. We therefore conclude that the gene which is responsible for the increased susceptibility to myasthenia gravis in women and which is present in the MHS region, is more closely linked to the SD-2 than to the LD-1 locus.
Epitopes↗
Inhibition of the mitogenicity of the carrier molecule results in loss of immunogenicity of a hapten-LPS conjugate.
Colistin methanesulfonate, a basic polypeptide similar to polymyxin E, has been shown to suppress the mitogenicity of lipopolysaccharide (LPS) from E. coli. It also inhibits the immunogenicity of a hapten-LPS conjugate. The inhibition was neither due to interference with the expression of hapten determinants, nor was it due to crossreactivity between the hapten and colistin methanesulfonate. As mitogenicity and immunogenicity was similarly affected, we conclude that activation of bursa-derived lymphocytes, in specific thymus-independent immune responses, does not take place in the absence of a mitogenic (non-Ig mediated) signal, thus supporting the hypothesis of the "one nonspecific signal" for B cell triggering.
Animals↗
Effects of some immunosuppressive procedures on myasthenia gravis.
Clinical Observations. A total of 53 MG patients have been treated with different immunosuppressive methods (alone or combined) with the following effects: Thymectomy was performed in 38 patients. The improvement was excellent in 15, and moderate or uncertain in 20. In three patients severe long-lasting deterioration followed the operation. ACTH treatment (n=32): Initial deterioration during the 5-7 days of heavy ACTH treatment (1000 IU) was followed by an improvement lasting on an average 4 months. The improvement was good or moderate in 78% of the patients. Betamethazone treatment has been tried in six patients where ACTH and azathioprine was ineffective. In four of these patients the results were excellent. Azathioprine treatment has been given to 26 patients for periods up to 7 years. An improvement is measurable after 6-12 weeks and it seems maximal after about 1 year. Of the 26, 80% responded favorable with reduction in the need for cholinesterase inhibitors. Severe complications were seen in three patients with one death. Drainage of thoracic duct lymph was initiated in 14 patients up to 4 weeks with rapid improvement lasting as long as drainage was performed. Long-termed effects of the drainage may be present, however. Retransfusion of homologous cell-free lymph precipitated a return of the myasthenic symptoms. Biochemical Studies on Myasthenic Lymph. Using a membrane preparation from the electric organ from Torpedo marmorata and tritiated Naja naja siamensis neurotoxin we demonstrated a decreasing binding of toxin to the receptor in the presence of MG lymph gamma-globulin fraction. Gammaglobulins from controls showed almost no inhibition of the neurotoxin binding. Immunological Studies. An increased frequency of HL-A1 and 8 was found in female patients. LD typing was also performed. During a period of three weeks of thoracic duct drainage 130X10(9) or about 10% of total number of lymphocytes in the body were removed. In the lymph an initial decrease in the proportion of thymus-derived lymphocytes (T cells) occurred, which was accompanied by a sequent increase in the proportion of bone-marrow-derived lymphocytes (B cells). Towards the end of drainage this effect was reverted. Mitogenic stimulation using lymphocytes from thoracic duct drainage revealed no differences as compared to normal cells. The proportions of T and B cells was studied in the peripheral blood in nine patients treated with ACTH. During treatment there was an initial decrease in the proportion of T cells accompanied by a subsequent rise in the proportion of B cells, which was maximal after 3-10 days. These proportions were reverted to normal 1-5 days after the maximal change. The effect of azathioprine on T and B cells has also been studied.
Adrenocorticotropic Hormone↗
Whole-body autoradiography of 99Tcm-labelled pyrophosphate and related compounds in young rats.
The distribution of 99Tcm-labelled pyrophosphate in young rats was analysed by wholebody autoradiography and compared with those observed for 99Tcm-pertechnetate, 32P-labelled pyrophosphate and 85Sr-chloride. 99Tcm-labelled pyrophosphate was rapidly accumulated in bone and dentine and was similar to 32P-labelled pyrophosphate and 85Sr-chloride. The uptake of these substances in developing enamel was rather low in contrast to 99Tcm-pertechnetate, which had no affinity for bone.
Animals↗