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Biomedical subjects

M B Pepys

Publications and source records attributed to M B Pepys.

At least 271 records · Page 15Linked to original sources
PubMed1980

Serum protein concentrations during Schistosoma mansoni infection in intact and T-cell deprived mice. I. The acute phase proteins, C3 and serum amyloid P-component (SAP).

Normal mice developed marked elevation of two acute phase plasma proteins, C3 and serum amyloid P-component (SAP), between 40 and 50 days after percutaneous infection with cercariae of Schistosoma mansoni. The high levels persisted until the end of the experiment (day 106). The onset of this acute phase response corresponds with the reported time at which granulomata develop in the liver. In mice deprived of T cells by thymectomy and anti-thymocyte serum, the granulomata were significantly smaller and all the animals died between days 70 and 80. These mice had normal C3 levels throughout although there was a rise in SAP concentration. C3 and SAP levels in infected control mice, which had been thymectomized but not deprived of T cells with anti-thymocyte serum, were the same as in intact infected animals. The different behaviour of C3 and SAP in infected T-cell deprived mice may reflect the alteration in specific schistosomal pathology and/or a role for T cells in mediation of the acute phase production of some proteins.

Amyloid↗
PubMed1980

Complement-independence of the acute-phase production of serum amyloijd P-component (SAP) in mice.

Mice depleted of circulating C3 by injection of cobra factor (CoF), the C3-activating protein of cobra (Naja naja) venom, mounted the same acute-phase responses of serum amyloid P-component (SAP) to subsequent injection of casein, bacterial lipopolysaccharide or croton oil as did normal control mice. There was also evidence for accelerated synthesis of C3 itself in response to injection of these acute-phase stimulants in CoF-treated mice. On the other hand complement activation produced by injection of CoF alone did not cause any elevation of the serum SAP level. These results indicate that acute-phase plasma protein production can proceed independently of the complement system as a mediator of or participant in inflammatory reactions, and that complement activation alone is not a sufficient stimulus for an acute-phase response, at least of SAP.

Amyloid↗
PubMed1980

Amyloid P-component in mice injected with casein: identification in amyloid deposits and in the cytoplasm of hepatocytes.

Amyloid P-component was sought by immunofluorescence in the tissues of CBA mice receiving repeated subcutaneous injections of casein. P-component appeared in a perifollicular distribution in the spleen after about twenty casein injections, and correlated precisely with amyloid deposits identified by staining with Congo red. In mice which had received at least fourteen injections of casein, P-component also became detectable within the cytoplasm of periportal hepatocytes. This is the first demonstration of P-component in murine amyloid and of a possible site for in vivo synthesis of P-component.

Amyloid↗
PubMed1980

Differences in the acute phase responses of serum amyloid P-component (SAP) and C3 to injections of casein or bovine serum albumin in amyloid-susceptible and -resistant mouse strains.

In CBA/Ca and C57Bl/Cbi mice, which are susceptible to casein-induced amyloidosis, daily injections of casein caused a marked rise in the level of circulating serum amyloid P-component (SAP), which was sustained while injections continued. In contrast, mice given bovine serum albumin (BSA) injections showed only a small, transient increase in SAP levels. A/J mice, which are relatively resistant to casein-induced amyloidosis, also developed high SAP levels initially, but the increase was not maintained despite continued administration of casein. A/J mice receiving BSA had a slowly progressive rise in SAP which reached the same level as in the casein-treated animals. Administration of colchicine, which prevents casein-induced amyloidosis, suppressed the SAP response to casein in CBA mice. The serum level of the C3 component of complement, which is not an amyloid protein but is an acute phase reactant, also increased following casein injection. The rise in C3 was, however, proportionately less than that of SAP, was less sustained and was scarcely affected by colchicine. The present results therefore demonstrate different patterns in the acute phase response of different proteins in different mouse strains, and suggest that there may be a relationship between sustained high levels of SAP and the deposition of amyloid.

Amyloid↗
PubMed1979

Immunodeficiency, malabsorption and secretory diarrhea. A new syndrome.

Described here is a patient with severe watery diarrhea associated with common variable immunodeficiency. Malabsorption for fat, bile acids, vitamin B12 and xylose was demonstrated, but the patient failed to respond to all the usual therapeutic maneuvers. The diarrhea responded only to high dose steroid therapy. Intestinal perfusion studies showed a hitherto undescribed, presumably acquired, glucose-stimulated water, sodium and chloride secretion in the jejunum and ileum, whereas normal fluid and electrolyte transport occurred from bicarbonate and mannitol solutions. Glucose absorption itself was normal and no hormonal, morphologic or biochemical defect was demonstrated to account for the phenomenon. The patient was also interesting when compared with other patients with common variable immunodeficiency in having normal plasma cells in the intestinal mucosa and an extensive family involvement.

Adult↗
PubMed1979

An improved method for the isolation from Naja naja venom of cobra factor (CoF) free of phospholipase A.

An improved method is reported for the isolation from cobra (Naja naja) venom of cobra factor (CoF), the anticomplementary protein which is derived from cobra C3. Sequential chromatography on DEAE-Sepharose, Sephacryl-S200, and finally hydroxylapatite yielded 6.25 mg CoF per gram of crude venom. The purified CoF had 1 unit of functional anticomplementary activity per 1--2 micrograms of protein, and was homogeneous on gradient and non-reduced sodium dodecyl sulphate (SDS) polyacrylamide gel electrophoresis (PAGE). In SDS-PAGE after reduction with mercaptoethanol there were two major bands (M.W. 75,000 and 51,000 daltons), three minor bands (M.W. 29--31,500 daltons) and two trace bands (36,500 and 41,500 daltons). By analogy with mammalian C3 it is suggested that the CoF consists of two polypeptide chains linked by disulphide bridges, one of which undergoes cleavage of the peptide chain at several points either in vivo or in vitro.

Animals↗
PubMed1979

Binding of serum amyloid P-component (SAP) by amyloid fibrils.

Serum amyloid P-component (protein SAP) was found to bind in vitro to isolated amyloid fibrils of both primary and secondary types. The binding was strictly calcium-dependent, optimal uptake requiring at least 0.5 mM calcium ion. Using normal human serum as the source of protein SAP different fibril preparations became saturated with between 5--20 micrograms of SAP per mg dry weight of fibril. Isolated pure protein SAP bound in greater amounts. In control experiments SAP did not bind significantly to collagen fibrils, sheep erythrocytes, plastic shavings, or the following immobilized proteins: human kappa or lambda Bence-Jones proteins; human; rabbit or mouse IgG; human serum albumin. C-reactive protein, which resembles protein SAP structurally but has calcium-dependent specificity for different ligands, bound significantly to only one of five different amyloid fibril preparations.

Amyloid↗
PubMed1979

Lymphocyte binding of fluid phase mouse C3b.

Isolated fluid phase mouse C3b adhered to human and to mouse lymphocytes. On human, but not on mouse cells it could be stained by fluoresceinated F(ab')2 anti-mouse C3. Binding to mouse cells was, however, shown by inhibition of C3-dependent rosette formation and by direct staining with fluorescein-conjugated C3b (FITC-mouse C3b). Optimal staining of lymphocytes by FITC-mouse C3b depended on a sufficient intensity of fluorochrome conjugation and on a degree of aggregation of the C3b. FITC-mouse C3b preparations which initially stained weakly, stained strongly after being aggregated with glutaraldehyde. The failure of immunofluorescent techniques to demonstrate binding by mouse lymphocytes of mouse C3b which had not been so aggregated was apparently due to inaccessibility to anti-C3 of the receptor-bound C3b. Aggregated mouse C3b-FITC induced sequential patching and capping of lymphocyte complement receptors followed by endocytosis, all of which was inhibited completely by cold (4 degrees), sodium azide (2 x 10(-3) m), cytochalasin B (28 microgram/ml) and chlorpromazine (10(-4) m), and partially by lignocaine (2 x 10(-3) m), and colchicine (10(-4) m). That mouse C3 which has interacted with mouse complement receptors may not be demonstrable by anti-C3 antibody may have important implications for immunohistochemical localization of C3 bound in vivo to lymphoid cells.

Animals↗
PubMed1979

Isolation of serum amyloid P-component (protein SAP) in the mouse.

Serum amyloid P-component (protein SAP) was associated from mouse serum and ascitic fluids by calcium-dependent affinity chromatography on Sepharose 4B (Pharmacia) followed by gel filtration on Ultrogel AcA44 (LKB) in the presence of EDTA. It was homogenous on gradient polyacrylamide gel and sodium dodecyl sulphate (SDS)-polyacrylamide gel electrophoresis, and induced a monospecific antiserum in the rabbit. The related protein, C-reactive protein (CRP) was present in only trace amounts not exceeding 2 mug/ml of serum even during acute phase reactions. It was isolated by calcium-dependent affinity chromatography on insolubilized pneumococcal C-polysaccharide. The availability of these isolated mouse proteins and their respective antisera will facilitate investigation of their function.

Amyloid↗
PubMed1979

Inhibition of complement-dependent rosette formation after lymphocyte incubation with fatty acids.

Overnight incubation of lymphocytes with certain fatty acids bound to albumin has previously been shown to modify the fatty acid composition of cellular phosphoglycerides without impairing viability, and also to inhibit mitogen and antigen-induced lymphocyte transformation. In the present study, incubation of human lymphocytes with palmitic acid or with linoleic acid impaired their capacity to form complement-dependent rosettes but had no effect on either spontaneous rosette formation with sheep erythrocytes or Fc(gamma)-dependent rosette formation. With mouse lymphocytes, complement-dependent rosette formation was suppressed only following incubation with linoleic acid and there was no effect on Fc(gamma)-dependent rosette formation. Although the mechanism of these effects remains to be elucidated the results suggest that control of membrane lipid composition may modify the important in vivo immunological functions which involve complement receptors.

Animals↗
PubMed1979

Activation of mouse complement by different classes of mouse antibody.

The capacity of mouse IgM, IgGl, IgG2 and IgA anti-dinitrophenyl (DNP) antibodies to activate mouse or guinea-pig complement was studied, using a sensitive haemolytic assay and two-dimensional immunoelectrophoresis to detect cleavage of mouse C3. Three monoclonal IgM antibodies, and a heterogeneous IgM fraction, lysed trinitrophenylated erythrocytes in the presence of guinea-pig C, but failed to produce lysis in the presence of mouse C. and only activated mouse C3 very inefficiently. A monoclonal IgGl antibody did not produce haemolysis in the presence of guinea-pig or mouse C, but cleaved mouse C3 via the alternative pathway. Two IgA myeloma proteins (M315 and M460) had similar properties. A heterogeneous IgG2 antibody fraction produced haemolysis in the presence of both mouse and guinea-pig C, and was shown to activate both the classical and alternative pathways of mouse C.

Animals↗
PubMed1978

Cell-mediated immunological responsiveness in mice decomplemented with cobra venom factor.

In vivo administration of cobra factor (CoF) the C3-activating protein of cobra venom, had no suppressive effect on the in vitro response of lymphocytes to PHA, LPS or allogeneic cells; nor did it affect the generation of cells cytotoxic to allogeneic target cells. HVG reactivity was inhibited by commercially available but not purified CoF, and the latter also failed to prolong skin allograft survival. It is concluded that in vivo complement depletion does not interfere with T cell responses, and that previous reports of prolonged survival of skin allografts and inhibition of cutaneous delayed hypersensitivity reactions following treatment with CoF may have been due to impurities in the preparations used.

Animals↗
PubMed1978

Comparative clinical study of protein SAP (amyloid P component) and C-reactive protein in serum.

The serum concentration of protein SAP (amyloid P component) has been measured for the first time in a substantial series of normal individuals and patients with various diseases, and the results contrasted with the levels of the related protein C-reactive protein (CRP). The mean +/- s.d. concentration of protein SAP was 43 +/- 14 microgram/ml in seventy-six normal men, 33 +/- 10 microgram/ml in eighty-six normal women and 4 +/- 2 microgram/ml in thirty-six normal cord sera. Unlike CRP, whick is a major acute phase reactant, protein SAP was only slightly elevated in inflammatory and neoplastic diseases in which CRP was greatly increased. The level of protein SAP was significantly depressed in patients with hepatic disease, suggesting that its measurement might be of value in their management.

Amyloid↗
PubMed1977

Temperature dependence of antigen-specific rosette formation by lymphocytes from immunised mice.

Spleen cell suspensions from mice undergoing a secondary response to sheep erythrocytes (SRBC) contained about one tenth as many specific antigen-binding, rosette-forming cells (RFC) when they had been washed at 37 degrees C instead of 4 degrees C before rosetting. This difference was correlated with the presence of IgG anti-SRBC antibody in the serum, and the 37 degrees C washings of immunised spleen cells could passively allergise non-immune spleen cells at 4 degrees C for specific rosette formation which was inhibitable by anti-mouse F(ab)2 serum. The RFC from actively immunised mice were lymphocytes and not macrophages by morphological and cytochemical criteria. It is suggested that the 37 degrees C-labile RFC are lymphocytes to which IgG antibodies bind in the cold. These data indicate that in the use of antigen-binding cell assays to monitor immunological responses, it is necessary to wash lymphocytes at 37 degrees C before testing.

Animals↗