Biomedical subjects
J L Ryan
Publications and source records attributed to J L Ryan.
Detection of a mediator derived from endotoxin-stimulated macrohpages that induces the acute phase serum amyloid A response in mice.
The mechanism by which LPS stimulates an acute phase serum amyloid A (SAA) response in C3H mice has been studied. A factor (SAA inducer) appears in the blood of C3H/HeN (lipopolysaccharide [LPS]-sensitive) mice approximately 1 h after administration of LPS, which, when passively administered, can induce C3H/HeJ mice to produce SAA although they are resistant to the LPS itself. SAA inducer has been detected in the culture medium of LPS treated C3H/HeN macrophages but not spleen cells. Thus, two stages in the induction of the acute phase SAA response are now recognized: a latent period of 2-3 h during which the SAA concentration remains at baseline values and in which SAA inducer appears, and the period of synthesis of SAA which lasts for approoximately 24 h past induction. It is proposed that a macrophage response to LPS is responsible for production of the serum mediator which induces SAA synthesis.
Possible role for glycosphingolipids in the control of immune responses.
Preparations of gangliosides from bovine brain contain material which acts as a strong mitogen on murine spleen cells. This material is highly lipophilic and co-purifies with the ganglioside fraction. It contains saccharides of a similar composition to those found in monosialogangliosides, as well as a spinogsine base and an appreciable amount of peptide. The common brain gangliosides GM1, GD1a and GD1b, on the other hand, are not mitogenic and act as suppressors of the mitogenic activity of bacterial lipopolysaccharide on murine spleen cells. Both the mitogenically active and suppressive fractions of bovine brain glycosphingolipid were found to act exclusively on B lymphocytes. Since gangliosides and related compounds are components of plasma membranes and of amphipathic nature, they may passively migrate between the lymphocyte subpopulations and thus act as physiological modulators of immune responses.
Bacterial endotoxins and host immune responses.
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Lack of responsiveness of C3H/HeJ macrophages to lipopolysaccharide: the cellular basis of LPS-stimulated metabolism.
The rate of glucose utilization has been used as a measure of LPS-induced activation of cultures of C3H/HeN and C3H/HeJ spleen cells, peritoneal cells, and purified peritoneal adherent cells. Peritoneal cells utilized 40 to 60 times more glucose than did spleen cells and purified adherent monolayers were more active than mixed peritoneal cells, suggesting that only macrophage metabolism was being measured. The cell preparations for C3H/HeJ mice were not activated by Escherichia coli K235 LPS prepared by extensive phenol extraction, whereas C3H/HeN cells were activated by the LPS. Cells from both strains were activated by a commercially obtained E. coli 0111:B4 LPS and butanol-extracted K235 LPS. The addition of 10% C3H/HeN spleen cells to C3H/HeJ peritoneal cells resulted in a marked enhancement of glucose utilization. These findings suggest that LPS-induced enhancement of macrophage metabolism occurs both by direct action of LPS on macrophages as well as indirectly through activated lymphocytes.
The influence of oxidation state on the absorption of plutonium from the gastrointestinal tract.
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Impaired response to pneumococcal vaccine in Hodgkin's disease.
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The CEO: Mr. Inside or Mr. Outside?
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C57BL/10/CR mice: nonresponders to activation by the lipid a moiety of bacterial lipopolysaccharide.
C57BL/10/CR mice do not respond to the lipid A moiety of LPS. This defect was demonstrated in vivo by a decreased production of the acute phase serum amyloid protein SAA. In addition, the defect was demonstrated in vitro by using cultures of spleen cells and peritoneal cells. No mitogenesis of spleen cells or enhanced glucose utilization by either spleen cells or peritoneal cells was observed when the cells were stimulated by lipid A or phenol-extracted Escherichia coli K235 LPS. The response of these mice to PHA, Con A, Poly I:C, 8BrcGMP, and butanol extraced E. coli K235 LPS was normal. Thus, the inability of lipid A to stimulate B lymphocyte mitogenesis and activate peritoneal cells in vitro may correlate with its inability to induce the acute phase SAA in vivo. B10/CR mice represent another strain, similar to the C3H/HeJ, which is nonresponsive to lipid A and should be useful in eludcidating the mechanism by which bacterial LPS activates cells.
Comparative evaluation of two new applanation tonometers-preliminary study.
Three separate intra-ocular pressure assessment preliminary studies utilising the Goldmann, E.M.T. 20 and the Digilab Model 30R pneumatonometer were carried out on a total of 114 eyes with glaucoma, and in 184 normal eyes in 162 patients. In general the E.M.T 20 gave a lower result that the Goldmann but both compared well within the normal intra-ocular pressure range. Within the normal intra-ocular pressure range the pneumatonometer generally gave a 1-3 mm Hg higher reading than the Goldmann but in the glaucomatous eyes this difference became much less and readings tended to be similar with both tonometers. The fixed calibration of the E.M.T. 20 and its accuracy for pressures in the 20 mm Hg range make it an ideal instrument for screening for glaucoma but it is not suitable for the accurate stabilization of glaucoma patients under treatment. The accuracy of the pneumatonometer in the range of intra-ocular pressure above 22 mm Hg render it the instrument of choice for the diagnosis and control of glaucoma patients. Added advantages of the pneumatonometer were the resilience of the probe to accidental damage and the ability to record the ocular pulse.
Genetic non-responsiveness of murine fibroblasts to bacterial endotoxin.
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Fc receptor-mediated inhibition of murine B-lymphocyte activation.
Immobilized antigen-antibody complexes are able to inhibit the mitogenic response of murine spleen cells to the B-cell mitogen 8-bromo-3',5'-cyclic guanosine monophosphoric acid. This this inhibition is dependent on intact Fc fragments in the immobilized complexes. Soluble complexes do not mediate this inhibition. When lipopolysaccharide (lps) activation of B cells was studied, it was found that the mitogenic response was inhibited at all times tested between 2 and 7 days of culture. Also, the LPS-induced mitogenesis of nude spleen cells was inhibited by immobilized complexes, indicating that suppressor T cells probably play no significant role in the inhibition. Immobilized complexes inhibit polyclonal antibody responses in a serum-free system and in the presence of normal mouse serum, but are unable to inhibit in the presence of fetal calf serum (FCS). If nu/nu spleen cells are used, however, the FCS does not block the ability of the complexes to inhibit the polyclonal response. It is suggested that that antigen-antibody complexes under appropriate conditions may bind to B lymphocytes via their Fc receptors and trigger a central "off" signal which blocks proliferation and consequently antibody production.
Inhibition of B lymphocyte activation by interaction with Fc receptors.
Much early work indicated that specific antibody can play an inhibitory role in the immune response. This inhibitory activity was found to be dependent on an intact Fc portion of the antibody used, both in vivo and in vitro. Thus a role for lymphocyte Fc receptors in regulations of the immune response was suggested. However, soluble antigen-antibody complexes, which bind to Fc receptors, do not appear to inhibit B cell activation. Recent experiments have demonstrated that antigen-antibody complexes immobilized on a surface strikingly inhibit LPS induced B cell mitogenesis and polyclonal antibody synthesis. Mechanisms for Fc receptor-mediated inhibition of B cell activation have been considered, and a model proposed to explain many of these findings as well as allow for antigen specific inhibition.
Inhibition of lymphocyte mitogenesis by immobilized antigen-antibody complexes.
Mouse spleen cells, cultured on surfaces coated with antigen-antibody complexes, are inhibited from responding to the B-cell mitogens, lipopolysaccharide, lipid A, Pneumococcal polysaccharide SIII, and poly I:C. The response to the T-cell mitogen, concanavalin A, is also substantially inhibited by immobilized antigen-antibody complexes, but specific inhibition of the response to phytohemagglutinin is minimal. Control experiments showed that immobilized complexes prepared from IgG F(ab')2 fragments and IgA antibodies (both of which fail to bind to Fc receptors when complexed to antigen) did not show significant inhibitory activity when compared with the inhibition observed with complexes prepared from whole IgG. Suspensions of antigen-antibody complexes prepared from the same antigen and intact IgG antibody did not inhibit mitogenesis. None of the mitogens used could be demonstrated to compete with the binding of aggregated immunoglobulin to the B-cell Fc receptor. It appears that the interaction of Fc receptor-bearing lymphocytes and/or macrophages with immobilized complexes prevents lymphocyte activation by mitogens. It is suggested that the mechanism(s) involved may be relevant to antibody feedback control of the humoral immune response.
Simple method for culturing anaerobes.
A simple, effective method is needed for growing obligate anaerobes in the clinical laboratory. This report describes a pre-reduced anaerobic bottle that can be taken to the bedside for direct inoculation, provides a flat agar surface for evaluation of number and morphology of colonies, and can be incubated in conventional bacteriological incubators. Each anaerobic culture set consisted of two bottles containing brain heart infusion agar and CO(2). Gentamicin sulfate (50 mug/ml) was added to one of these to inhibit facultative enteric bacilli. Comparison of the anaerobic bottles with an identical aerobic bottle which was also routinely inoculated permitted early identification of anaerobic colonies. Representative species of most anaerobic genera of proven pathogenicity for man have been isolated from this system during 10 months of routine use.
Galactose-deficient endotoxin from urinary Escherichia coli.
Analysis of 111 rough strains of Escherichia coli from known urinary infections revealed for the first time that galactose-deficient rough mutants are not exclusively a laboratory phenomenon. They exist naturally with or without an epimerase deficiency and represent natural examples of the key role of galactose in the attachment of "O" side chains to the core of bacterial lipopolysaccharides.
Medical ethics and the civil law.
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Pressures for change. The financial pressures.
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