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Biomedical subjects

C I Smith

Publications and source records attributed to C I Smith.

At least 325 records · Page 18Linked to original sources
PubMed1978

Functional characterization of lanatoside-C-responsive cells.

Lanatoside C, a digitalis glycoside previously shown to be a polyclonal B-cell activator (PBA), was found to stimulate immature cells residing in fetal liver, bone marrow and spleen but also to activate cells from peripheral lymph nodes and peripheral blood. The proliferative response obtained in spleen cells was not affected by macrophage removal, whereas anti-Ig or anti-Ia antiserum pretreatment partially inhibited the responses. Removal of T cells by a pretreatment with anti-Thy 1.2 antiserum plus complement caused a marked increase in the proliferative response of the remaining cells, suggesting the existence of a naturally occurring suppressor T cell for glycoside-induced mitogenesis. Synergy experiments with 'classical' PBAs and lanatoside C, given simultaneously or subsequently, suggest an overlap between the lanatoside-C-responding cell population and the dextran sulphate (DxS)- and lipopolysaccharide (LPS)-sensitive cells. Since DxS-induced activation of B cells is dependent on macrophages, it is suggested that lanatoside C may be used as a functional marker for direct activation of immature B cells.

Animals↗
PubMed1978

Different requirements for T cells responding to various doses of concanavalin A.

Con A is known to activate T cells to proliferation and the development of effector cells. Conflicting reports have been published as to the need for accessory cells in the T-cell response induced by Con A. We have found that the proliferative response in purified mouse spleen T cells induced by various doses of Con A requires different culture conditions and helper cells. The Con-A-induced response induced by optimal and high concentrations of the ligand requires the presence of either serum or adherent cells obtained from the peritoneal cavity or the spleen. For induction of a proliferative response by low doses of Con A both serum and helper cells must be present. The T-cell response to suboptimal concentrations of Con A is further characterized by the fact that the presence of an Ia-positive cell is required. Removal of Ia-positive cells from purified T cells results in a loss of the response of remaining cells to low doses of Con A but has less effect on the response induced by higher concentrations of the activating ligand. The possibility that distinct subsets of T cells are responding to low and high concentrations of Con A will be discussed.

Animals↗
PubMed1978

A chemical approach to the mechanism of B-lymphocyte activation. I. The pure presentation of haptens does not activate B lymphocytes.

In an attempt to definitively determine whether the pure presentation of haptens (on repetitive, non-metabolizable carriers) to B lymphocytes triggers differentiation to antibody-producing cells, dinitrophenyl and trinitrophenyl groups have been covalently coupled to potentially inert carriers (polymethylmethacrylate, chlorinated polyethylene and cellulose). The resulting conjugates (with three different degrees of hapten substitution) are not immunogenic. It is therefore concluded that the pure presentation of haptens to B lymphocytes does not trigger antibody formation.

Acrylic Resins↗
PubMed1978

HLA-A, -B, -C and -D antigens in male patients with myasthenia gravis.

HLA-A, -B, -C and -D antigens were determined in 54 male Myasthenia Gravis patients. A significant increase of the B8 antigen frequency was found among patients with an onset of the disease before the age of 35. No significant increase was found among the D antigens. In a combined male and female material with an early age at onset, thymic hyperplasia was correlated to the presence of HLA-B8.

Adult↗
PubMed1978

No significant correlation of HLA-B8 and amount of antibodies directed to acetylcholine receptor protein in patients with myasthenia gravis.

Forty patients with myasthenia gravis were HLA tissue typed and the amount of anti-acetylcholine receptor protein antibody determined. Sera from seven patients were tested for antibody titer by repeated determinations and the serum concentration was found to be stable. Patients with thymoma had higher titers than patients with normal thymus histology or hyperplasia. Individuals with thymoma lacking HLA-B8 were found to have a higher concentration of antibodies than HLA-B8 negative individuals with hyperplasia. No statistically significant differences were obtained when comparing the amount of antibody in HLA-B8 positive and negative individuals. Titers in patients subjected to thymectomy more than 8 years before sampling did not deviate from those in non-thymectomized myasthenics.

Acetylcholine↗
PubMed1978

Role of virus for the induction of myasthenia gravis.

Virus has been suggested as an etiological agent in myasthenia gravis. In this investigation 36 patients with the clinical diagnosis of myasthenia gravis were tested for antibodies against ornithosis, mycoplasma pneumoniae and 16 viral antigens. Rabbits with experimentally induced autoimmune myasthenia gravis were similarly tested. There was no overall correlation to any microorganism, which might have suggested the involvement of a viral infection in the pathogenesis of the disease. Neither was there any difference in incidence of antibodies in female patients carrying the HLA B8 antigen, an antigen which is associated with myasthenia gravis, as compared to HLA B8 negative individuals.

Adolescent↗
PubMed1978

Sodium polyanethole sulfonate: a new macrophage-dependent polymyxin-inhibitable, polyclonal B cell activator.

The anionic detergent sodium polyanethole sulfonate was found to activate mouse B lymphocytes to increased cell division and formation of plaque-forming cells, possibly by an indirect mechanism. An increased cell division was also obtained in guinea pig and in rabbit lymphooid cell cultures. A strong similarity was found when comparing the dextran sulfate- and the sodium polyanethole sulfonate-sensitive cell population. Thus, the responding mouse cells resided in spleen and lymph node and also in fetal liver and bone marrow. The sensitive lymphocytes were dependent on the presence of macrophages or macrophage-replacing factors, since depletion of phagocytic cells resulted in loss of response. Addition of polymyxin B inhibited the stimulation, possibly through a direct interaction with the polyanion. In potency sodium polyanethole sulfonate was found to surpass dextran sulfate, making this benzene sulfonate a useful tool when studying lymphocyte responses.

Animals↗
PubMed1978

Molecular basis of B cell activation: mitogenicity of native and modified digitalis glycosides.

Lanatoside C, a digitalis glycoside, has previously been shown to be a potent polyclonal B cell activator for mouse lymphocytes. Since the chemical structure of lanatoside C is well defined we investigated the effect of different chemical modifications on the mitogenic properties of the glycoside in order to determine the molecular basis of B cell activation. The presence of an OH- group at C12 in the steroid nucleus proved to be essential for activation to occur in serum-free medium. Likewise, an intact carbohydrate side chain at C3 appeared to be necessary for retaining mitogenic properties. In serum-supplemented cultures, however, a much more complex response pattern was observed where the prerequisites for activation were not as distinct as in serum-free medium.

Animals↗
PubMed1978

Genetic control of lymphocyte suppression. I. Lack of suppression in aged NZB mice is due to a B cell defect.

Con A-activated cells from old NZB mice were found capable of inhibiting the polyclonal response of cells from young NZB and BALB/c animals. Furthermore, Con A-preactivated spleen cells from young NZB and BALB/c mice did not significantly affect the response of spleen cells from old NZB mice. These results suggest that the defective suppressive activity in old NZB mice may be traced to a defect at the B cell level.

Aging↗
PubMed1977

Characterization of self-reactive B cells by polyclonal B-cell activators.

The existence of autoreactive B cells was predicted by theoretical considerations and, recently, confirmed by direct experiments. The aim of the present work was to investigate if the capacity of self-reactive B cells to be activated with different polyclonal B-cell activators (PBA) reflects the heterogeneity of the response as seen in all the Ig-positive cells. We injected mice with dextran sulfate, lipopolysaccharide from Escherichia coli 055:B5, and purified protein derivate of turbercle bacteria RT32 and studied the complement-dependent cytotoxicity against syngeneic spleen cells caused by the sera from injected mice with regard to the different parameters used for characterization of B-cell subpopulations. It was found that the capacity of self-reactive B cells to secrete antibodies reflects the polyclonal-activating capacity of the PBA used. The implications of these findings for the understanding of the triggering mechanism of B lymphocytes and for self-nonself discrimination are discussed.

Animals↗
PubMed1977

Immunological abnormalities associated with liver disease: cause or effect?

Immunological abnormalities are demonstrable in patients with various types of liver damage. These may be (a) non-specific and unrelated to pathogenesis, e.g. auto-antibodies such as anti-nuclear factor; (b) specifically directed against liver antigens but not pathogenetic, e.g. cell mediated immune (CMI) reactions to liver antigen as seen in experimental carbon tetrachloride poisoning; (c) of such a nature as to modify the pathology produced by hepatotoxic agents, e.g. hepatitis B virus or alcohol; (d) primarily responsible for hepatic pathology, e.g. in idiopathic chronic active hepatitis. The latter two possibilities remain unproven although there is growing evidence that immune responses do play some role in the pathogenesis of acute and chronic hepatitis B and possibly also in the pathogenesis of alcoholic liver disease. It seems much less likely that primary abnormalities of the immune systems are responsible for any type of liver disease. In summary, therefore, the available evidence suggests that immune reactions could develop as a consequence of liver damage and only in certain circumstances do these reactions play a role in the development and continuation of hepatic pathology.

Animals↗
PubMed1977

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↗
PubMed1977

Macrophages are required for the dextran-sulfate induced activation of B lymphocytes.

The proliferative response induced by the B cell activating ligand dextran-sulfate (DxS) requires the presence of macrophage-produced factors or the macrophage-substituting compound 2-mercaptoethanol. Thus, the mechanism for activation of mouse B splenic lymphocytes is different for DxS than for other polyclonal B cell activators such as lipopolysaccharides, which can trigger B cells directely in the absence of the helper factors. It is suggested that the disappearance of the DxS-induced response could be studied in a simple functional tests for the efficiency of macrophage depletion obtained by different techniques.

Animals↗
PubMed1977

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↗