184 results on '"Dumonde, D. C."'
Search Results
2. Adhesion molecules are upregulated on dendritic cells isolated from human blood
- Author
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McCARTHY, D. A., MACEY, M. G., BEDFORD, P. A., KNIGHT, S. C., DUMONDE, D. C., and BROWN, K. A.
- Published
- 1997
3. Human blood dendritic cells: binding to vascular endothelium and expression of adhesion molecules
- Author
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Brown, K. A., Bedford, P., Macey, M., McCarthy, D. A., Leroy, F., Vora, A. J., Stagg, A. J., Dumonde, D. C., and Knight, S. C.
- Published
- 1997
4. METALLOPROTEINASES AND TIMP-1 IN PROLIFERATIVE VITREORETINOPATHY: O159
- Author
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Limb, G A, Miller, K, Chignell, A H, Williamson, T H, Hollifield, R D, and Dumonde, D C
- Published
- 1996
5. Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-α)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression
- Author
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Vora, A. J., Perkin, G. D., McCoy, T., Dumonde, D. C., and Brown, K. A.
- Published
- 1996
6. IL-6 acts on endothelial cells to preferentially increase their adherence for lymphocytes
- Author
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Watson, C., Whittaker, S., Smith, N., Vora, A. J., Dumonde, D. C., and Brown, K. A.
- Published
- 1996
7. The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-beta1) up-regulation and increased prostaglandin E2 (PGE2) production
- Author
-
Harbige, L S, Layward, L, Morris-Downes, M M, Dumonde, D C, Amor, S, Pathology, Amsterdam Neuroscience - Neuroinfection & -inflammation, and AII - Inflammatory diseases
- Abstract
Polyunsaturated fatty acids are known to affect the immune response and administration of the omega-6 fatty acid linoleic acid has been reported to be beneficial in multiple sclerosis (MS) and EAE. In this study we have investigated the effects of oral feeding of plant lipid rich in the omega-6 fatty acid gamma-linolenic acid from Borago officinalis on acute and relapse disease and the immune response in EAE using SJL mice. EAE was induced by an encephalitogenic peptide (92-106) of myelin oligodendrocyte glycoprotein (MOG), and mice were fed the plant lipid daily from 7 days after EAE induction to assess the effects on acute disease and from day 25 to assess the effects on disease relapse. The clinical incidence and histological manifestations of acute EAE, and the clinical relapse phase of chronic relapsing EAE (CREAE) were markedly inhibited by omega-6 fatty acid feeding. A significant increase in the production of TGF-beta1 in response to concanavalin A (Con A) at day 13 and a significant increase in TGF-beta1 and PGE2 to Con A, PPD and MOG peptide (92-106) at day 21 were detected in spleen mononuclear cells from fatty acid-fed mice. There was no difference in interferon-gamma, IL-4 and IL-2 production between the fatty acid-fed and control groups. Significantly higher TGF-beta mRNA expression was found in the spleens of omega-6 fatty acid-fed mice at day 21. There were no differences in spleen cell proliferative response to Con A, PPD and MOG peptide (92-106). Biochemical analysis of spleen cell membrane fatty acids revealed significant increases in the eicosanoid precursor fatty acids dihomo-gamma-linolenic acid and arachidonic acid in response to gamma-linolenic acid feeding, indicating rapid metabolism to longer chain omega-6 fatty acids. These results show that oral feeding of gamma-linolenic acid-rich plant lipid markedly affects the disease course of acute EAE and CREAE and is associated with an increase in cell membrane long chain omega-6 fatty acids, production of PGE2 and gene transcription and, on activation, secretion of TGF-beta1.
- Published
- 2000
8. Selective up-regulation of human granulocyte integrins and complement receptor 1 by cytokines
- Author
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Gloria Astrid Limb, Hamblin, A. S., Wolstencroft, R. A., and Dumonde, D. C.
- Subjects
Integrins ,Antigens, CD ,CD11 Antigens ,CD18 Antigens ,Dose-Response Relationship, Immunologic ,Receptors, Complement 3b ,Cytokines ,Humans ,Cycloheximide ,Cells, Cultured ,Research Article ,Granulocytes ,Receptors, Complement - Abstract
The percentage of human granulocytes expressing the integrins CD11b and CD11c as well as complement receptor 1 (CD35) was increased by short-term incubation of whole blood with interleukin-2 (IL-2), interleukin-4 (IL-4) and tumour necrosis factors alpha and beta (TNF-alpha and TNF-beta). The mean fluorescence intensity of granulocyte CD18 was also increased by the above cytokines, whilst that of CD11b was only increased by TNF-alpha. Up-regulation of granulocyte CD18 expression was seen with 1 U/ml of IL-2, TNF-alpha or TNF-beta, in contrast to the effect of IL-4 which was only observed with 100 U/ml. Similarly, enhanced expression of CD35 was induced by 1 U/ml of IL-2 or TNF-alpha but not by concentrations of IL-4 or TNF-beta lower than 100 U/ml. Cytokine effects on the CD11/CD18 complex and CD35 molecules were not modified by cycloheximide, suggesting that their increased expression was not due simply to synthesis de novo. None of the granulocyte surface determinants investigated was altered upon short-term incubation of blood with either IL-1, IL-6 or interferon-gamma (IFN-gamma). The demonstration in vitro that cytokines selectively up-regulate granulocyte integrins and complement receptor 1, suggests that similar mechanisms may be operating during the control of granulocyte-mediated inflammatory processes.
- Published
- 1991
9. The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-β1) up-regulation and increased prostaglandin E2 (PGE2) production
- Author
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Harbige, L S, primary, Layward, L, additional, Morris-Downes, M M, additional, Dumonde, D C, additional, and Amor, S, additional
- Published
- 2000
- Full Text
- View/download PDF
10. Enhanced binding of lymphocytes from patients with multiple sclerosis to tumour necrosis factor-alpha (TNF-alpha)-treated endothelial monolayers: associations with clinical relapse and adhesion molecule expression
- Author
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VORA, A. J., primary, PERKIN, G. D., additional, McCOY, T., additional, DUMONDE, D. C., additional, and BROWN, K. A., additional
- Published
- 1996
- Full Text
- View/download PDF
11. Heat shock protein peptides reactive in patients with Behçet's disease are uveitogenic in Lewis rats
- Author
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STANFORD, M R, primary, KASP, E, additional, WHISTON, R, additional, HASAN, A, additional, TODRYK, S, additional, SHINNICK, T, additional, MIZUSHIMA, Y, additional, DUMONDE, D C, additional, VAN DER ZEE, R, additional, and LEHNER, T, additional
- Published
- 1994
- Full Text
- View/download PDF
12. Soluble intercellular adhesion molecule-1 (sICAM-1) as a marker of disease relapse in idiopathic uveoretinitis
- Author
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ZAMAN, A G, primary, EDELSTEN, C, additional, STANFORD, M R, additional, GRAHAM, E M, additional, ELLIS, B A, additional, DIRESKENELI, H, additional, D'CRUZ, D P, additional, HUGHES, G R V, additional, DUMONDE, D C, additional, and WALLACE, G R, additional
- Published
- 1994
- Full Text
- View/download PDF
13. Circulating immune complexes may play a regulatory and pathogenic role in experimental autoimmune uveoretinitis
- Author
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KASP, E, primary, STANFORD, M R, additional, BROWN, E, additional, COOMBES, A G A, additional, and DUMONDE, D C, additional
- Published
- 1992
- Full Text
- View/download PDF
14. Cytokines in proliferative vitreoretinopathy
- Author
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Limb, G A, primary, Little, B C, additional, Meager, A, additional, Ogilvie, J A, additional, Wolstencroft, R A, additional, Franks, W A, additional, Chignell, A H, additional, and Dumonde, D C, additional
- Published
- 1991
- Full Text
- View/download PDF
15. Molecular size of retinal vascular leakage determined by FITC-dextran angiography in patients with posterior uveitis
- Author
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Atkinson, E G, primary, Jones, S, additional, Ellis, B A, additional, Dumonde, D C, additional, and Graham, E, additional
- Published
- 1991
- Full Text
- View/download PDF
16. The protective effects of omega-6 fatty acids in experimental autoimmune encephalomyelitis (EAE) in relation to transforming growth factor-beta 1 (TGF-β1) up-regulation and increased prostaglandin E2 (PGE2) production.
- Author
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Harbige, L. S., Layward, L., Morris-Downes, M. M., Dumonde, D. C., and Amor, S.
- Subjects
OMEGA-6 fatty acids ,ENCEPHALOMYELITIS ,TRANSFORMING growth factors-beta ,PROSTAGLANDINS E ,MULTIPLE sclerosis - Abstract
Polyunsaturated fatty acids are known to affect the immune response and administration of the omega-6 fatty acid linoleic acid has been reported to be beneficial in multiple sclerosis (MS) and EAE. In this study we have investigated the effects of oral feeding of plant lipid rich in the omega-6 fatty acid gamma-linolenic acid from Borago officinalis on acute and relapse disease and the immune response in EAE using SJL mice. EAE was induced by an encephalitogenic peptide (92–106) of myelin oligodendrocyte glycoprotein (MOG), and mice were fed the plant lipid daily from 7 days after EAE induction to assess the effects on acute disease and from day 25 to assess the effects on disease relapse. The clinical incidence and histological manifestations of acute EAE, and the clinical relapse phase of chronic relapsing EAE (CREAE) were markedly inhibited by omega-6 fatty acid feeding. A significant increase in the production of TGF-β1 in response to concanavalin A (Con A) at day 13 and a significant increase in TGF-β1 and PGE
2 to Con A, PPD and MOG peptide (92–106) at day 21 were detected in spleen mononuclear cells from fatty acid-fed mice. There was no difference in interferon-gamma, IL-4 and IL-2 production between the fatty acid‐fed and control groups. Significantly higher TGF-β mRNA expression was found in the spleens of omega-6 fatty acid-fed mice at day 21. There were no differences in spleen cell proliferative response to Con A, PPD and MOG peptide (92–106). Biochemical analysis of spleen cell membrane fatty acids revealed significant increases in the eicosanoid precursor fatty acids dihomo-γ-linolenic acid and arachidonic acid in response to gamma-linolenic acid feeding, indicating rapid metabolism to longer chain omega-6 fatty acids. These results show that oral feeding of gamma-linolenic acid-rich plant lipid markedly affects the disease course of acute EAE and CREAE and is associated with an increase in... [ABSTRACT FROM AUTHOR]- Published
- 2000
- Full Text
- View/download PDF
17. Heterogeneity of guinea-pig lymphokines revealed by parallel bioassay.
- Author
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Bray, M. A., Dumonde, D. C., Hanson, Jennifer M., Morley, J., Wolstencroft, R. A., and Smart, J. V.
- Subjects
- *
LYMPHOKINES , *BIOLOGICAL assay , *MACROPHAGES , *ANTIGENS , *GUINEA pigs as laboratory animals , *IMMUNOLOGY - Abstract
This paper describes the application of parallel bioassay to the measurement of lymphocyte mitogenic, inflammatory and macrophage migration inhibitory activities present in guinea-pig lymphokine preparations. Seven lymphokine preparations were made under similar conditions by antigen activation of sensitized guinea-pig peritoneal exudate cells; and one of these was prepared in sufficient quantity as a 'working standard' for the repeated assay of the three lymphokine activities in the other six 'test' preparations. Mean potency ratios of the separate lymphokine activities were calculated for the test preparations by reference to those of the standard preparation (designated as unity). Although the seven preparations were made under operationally similar circumstances, χ² analysis of the assay results revealed that the three separate lymphokine activities occurred in different absolute amounts and relative proportions in the different preparations. This demonstration by parallel bioassay of heterogeneity and dissociation of lymphokine activities implies that these biological activities cannot be ascribed to a single substance. This type of analysis has general application in the characterization and separation of biologically active substances present in preparations exhibiting multiple activities. [ABSTRACT FROM AUTHOR]
- Published
- 1976
18. Experimental cutaneous leishmaniasis.
- Author
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Preston, Patricia M. and Dumonde, D. C.
- Subjects
- *
LEISHMANIASIS , *PROTOZOAN diseases , *IMMUNOGLOBULINS , *PLASMA cells , *IMMUNITY , *ANTIGENS - Abstract
This study shows how infection of CBA mice with L. tropica can be manipulated so as to mimic the principal features of both subclinical and self-healing cutaneous leishmaniasis in man. CBA mice were infected with graded inocula of L. tropica promastigotes. The pattern of primary infection was found to be dependent on dose of infecting organisms: mice given low dose inocula (10², 10³) developed subclinical infections: those given high dose inocula (104, 105, 106) developed overt, clinical lesions. Size and duration of lesions, and antibody production were directly proportional to dose: delayed hyper- sensitivity responses were inversely proportional to dose. Protective immunity to challenge infection was induced by both subclinical and clinical infection: and was manifest both during and after the healing stages of primary lesions. Protective immunity was also induced by artificial immunization with sonicated promastigotes in adjuvants but was only manifest if the challenge dose was not too large. The course of challenge infections differed depending on the method of immunization, i.e. whether by infection or artificial immunization. Lymphoid cells from immune CBA mice conferred protection on recipient syngeneic CBA mice against challenge infection; serum from immune mice did not, but suspension of immune peritoneal cells in immune serum enhanced their protective capacity. The experimental induction of protective immunity by low-dose infection, without a clinical allergic response at the site of inoculation, is of importance in designing an immunoprophylactic approach to human leishmaniasis. [ABSTRACT FROM AUTHOR]
- Published
- 1976
19. Precipitation of experimental autoallergic uveoretinitis by cyclosporin A withdrawal: an experimental model of uveitis relapse.
- Author
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Atkinson, E. G., Dinning, W. J., Kasp, E., Graham, E. M., and Dumonde, D. C.
- Subjects
CYCLOSPORINE ,CYCLIC peptides ,UVEITIS ,EYE inflammation ,UVEAL diseases ,LABORATORY mice - Abstract
This study set out to determine whether withdrawal of cyclosporin A (CyA) in Lewis rats sensitized to retinal S antigen would precipitate experimental autoallergic uveoretinitis (EAU), and whether challenge of such animals with S antigen or an unrelated stimulus would accelerate EAU onset after drug withdrawal. Rats were sensitized with 50 μg S antigen in Freund's complete adjuvant (FCA) and EAU onset was suppressed by 18 days of treatment with CyA at doses ranging from 3 to 10 μg/kg daily. Without challenge, seven out of 11 animals developed EAU with a median onset of 78 days, This was reduced to 6S days in rats challenged on day 32 with FCA alone, to 48 days with 10 μg S antigen in FCA. and to 41 days with 50 μg S antigen in FCA. The incidence, onset and severity of anterior uveitis and extent of photoreccptor destruction were related to both CyA dose and nature of challenge. The extent of photoreceptor destruction ran parallel with severity of anterior uveitis; and delayed-type hypersensitivity reactivity on day 43 was related to both severity of anterior uveitis (P<0.001) and photoreceptor damage (P<0.02). At the highest dose. CyA also delayed the appearance of antibody to S antigen; however, subsequent antibody levels were unrelated to EAU severity or to nature of challenge. The results indicate that CyA-induced suppression of the immunological response to S antigen can recover spontaneously after drug withdrawal, that challenge with either S antigen or FCA alone can accelerate the subsequent onset of EAU. and that these phenomena may provide a basis for investigating mechanisms underlying relapse of human uveoretinitis. [ABSTRACT FROM AUTHOR]
- Published
- 1989
20. Morphometric analysis of T lymphocyte compartmentation in experimental autoimmune uveoretinitis.
- Author
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Brown, E. C., Kasp, E., and Dumonde, D. C.
- Subjects
T cells ,LYMPHOCYTES ,CELLS ,RETINA ,GENOTYPE-environment interaction ,LEUCOCYTES - Abstract
Experimental autoimmune uveoretinitis (EAU) in the Lewis rat is characterized by extensive infiltration of inflammatory cells into all compartments of the eye, only some of which become irreversibly damaged. The apparent differences in the pathogenic impact of inflammatory cells within different ocular compartments may suggest that different mechanisms underlie cellular infiltration and selective tissue destruction. In order to investigate the importance of T lymphocyte infiltration, we carried out a precise topographical and temporal analysis of T cell infiltration into five compartments of the eye using an improved method for the fixation of ocular tissue. Our study showed that T cell infiltration began in the ciliary body and was most numerous and sustained in this area during EAU. The peak of T cell infiltration into the retina was comparatively delayed and was of lesser magnitude. Analysis of T cell subsets revealed a tendency for the helper phenotype to predominate during the course of disease in all ocular compartments except the retina where both helper and cytotoxic/suppressor T cells were equally represented at the height of inflammation. We suggest that the pathogenetic impact of autoreactive lymphocytes in EAU depends on the accessibility of relevant tissue antigen and on local microenvironmental features of lymphocytic traffic within different ocular compartments. [ABSTRACT FROM AUTHOR]
- Published
- 1989
21. Heat--induced aggregated human IgG modifies the adherence of human polymorphonuclear cells to cultured endothelium.
- Author
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Brown, K. A., McCarthy, D., Bull, M., Chasty, R. C., and Dumonde, D. C.
- Subjects
IMMUNOGLOBULIN G ,BLOOD plasma ,ENDOTHELIUM ,EPITHELIUM ,SURGICAL complications ,SERUM - Abstract
The adherence of human blood polymorphonuclear cells (PMNC) to cultured porcine aortic endothelium was enhanced by high concentrations of heat-stable IgG aggregates (HAGG) when sera was omitted from the culture media. With 20% human serum present in the media, HAGG induced a dose-related inhibition of PMNC adhesions with concentrations as low as 10 /(g/ml producing a significant effect. This inhibitory action of HAGG, which was optimally expressed after 30 min of incubation, seemed to be directed at the PMNC rather than the endothelium. Heat-inactivation of the sera resulted in a marked decline of the inhibitory activity of HAGG. Aggregates of size 15-21 s were demonstrated to be most effective in inhibiting PMNC attachment and it is complexes of this size which are commonly found in the circulation of patients with chronic inflammatory diseases. Immune complex modification of PMNC adherence may control leucocyte extravasation during inflammation. [ABSTRACT FROM AUTHOR]
- Published
- 1989
22. Shedding and synthesis de novo of Fc and C3b receptors by cultured guinea-pig macrophages.
- Author
-
Limb, G. A., Brown, K. A., Wolstencroft, R. A., and Dumonde, D. C.
- Subjects
MACROPHAGES ,GUINEA pigs as laboratory animals ,CULTURES (Biology) ,ERYTHROCYTES ,GENE expression ,FC receptors - Abstract
Resident macrophages freshly obtained from the peritoneal cavity of guinea-pigs were demonstrated to form a higher percentage of Fc and C3b rosettes than elicited macrophages when low concentrations of IgG and IgM-C3b were used to sensitize ox red blood cells (ORBC) in rosette assays. Culture of the total resident and elicited macrophages for 6 h at 37 °C resulted in a decrease of Fc and C3b rosette-forming cells, the loss of Fc receptor-bearing cells by resident macrophages only being apparent when using a sub-optimal concentration of sensitizing IgG. After 24 h incubation the percentages of Fc and C3b rosettes returned to their initial values. In contrast, there was no decline in the percentage of Fc and C3b rosettes formed by the adherent population of resident and elicited macrophages cultured for 6 h. However, extending the incubation of the adherent macrophage to 24 h produced an increase of Fc receptor-positive cells and a dramatic decrease of C3b receptor-positive cells. Culture supernatants of the total macrophage population that had been incubated for 6 h inhibited Fc and C3b rosette formation by freshly obtained elicited macrophages. These results, together with the demonstration that treatment of the total macrophage population with cycloheximide led to an inhibition of Fe and C3b receptor expression after 24 h culture, suggest that the Fc and C3b receptors of guinea-pig macrophages are shed and synthesized de novo during short-term culture. This system could be applied to the study in vitro of soluble immunoregutatory mediators on macrophage functions which are dependent on the expression of Fe and C3b receptors. [ABSTRACT FROM AUTHOR]
- Published
- 1988
23. Failure of exogenous interleukin 1 and interleukin 2 to correct decreased lymphocyte transformation in chronic hepatitis B virus carriers.
- Author
-
Anastassakos, Ch., Alexander, G. J. M., Wolstencroft, R. A., Dumonde, D. C., Eddleston, A. L. W. F., and Williams, R.
- Subjects
INTERLEUKIN-1 ,INTERLEUKIN-2 ,LYMPHOCYTES ,HEPATITIS B virus ,INDOMETHACIN ,PROSTANOIDS - Abstract
To test the hypothesis that reduced lymphocyte transformation in response lo PHA in chronic hepatitis B virus infection might be due lo deficient lymphokine production, lymphocyte transformation was measured in the presence or absence of exogenous interluekin I, interleukin 2 or both, or, as a source of mixed lymphokines, supernatants from mixed lymphocyte reactions. The response lo PHA was significantly impaired in patients compared lo controls, but was not corrected by interleukin 1. interleukin 2 or supernatant from mixed lymphocyte reactions over a wide range of concentrations. Variation of the proportion of monocytes in culture or the addition of indomethacin had no effect on lymphocyte transformation. Thus, reduced lymphocyte proliferation in response to PHA in patients with chronic hepatitis B virus infection cannot be attributed to deficient lymphokine production or to active suppression by monocytes or prostaglandins and a direct role for the hepatitis B virus or a viral product is under investigation. [ABSTRACT FROM AUTHOR]
- Published
- 1987
24. Interleukin 1 in Crohn's disease.
- Author
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Satsangi, J., Wolstencroft, R. A., Cason, J., Ainley, C. C., Dumonde, D. C., and Thompson, R. P. H.
- Subjects
INTERLEUKIN-1 ,MONOKINES ,CROHN'S disease ,ULCERATIVE colitis ,ILEUM diseases ,INFLAMMATORY bowel diseases - Abstract
A number of the activities currently ascribed to the mediator interleukin I (IL-1) are relevant to chronic inflammatory bowel disease. Using the mouse thymocyte stimulation assay, lymphocyte-activating factor (LAF ) activity was measured in plasma samples and supernatants from cultures of peripheral blood mononuclear cells from 16 patients with Crohn's disease, six with ulcerative colitis, and 10 healthy subjects. Results were compared with disease activity, drug therapy, granulocyte count, and plasma levels of zinc and C-reactive protein (CRP), Very low levels of LAF were detected in a few plasma samples from each of the subject groups. Mononuclear cells from healthy subjects produced LAF only when cultured with lipopolysaccharide, but stimulated ceils from patients produced greater amounts. Moreover, cells from six patients with Crohn's disease, not receiving steroids, produced LAF spontaneously. Crohn's disease patients also had low plasma zinc but elevated levels of CRP and granulocytes. This enhanced production of LAF in vitro may reflect a primary cellular defect in Crohn's disease, or a secondary consequence of monocyte activation. [ABSTRACT FROM AUTHOR]
- Published
- 1987
25. Experimental cellular allergic reactions in normal canine and malignant human prostate.
- Author
-
Robinson, M. R. G., Rigby, C. C., Pugh, R. C. B., Vaughan, L C., and Dumonde, D. C.
- Subjects
PROSTATE ,CANCER patients ,MYCOBACTERIUM tuberculosis ,BACTERIAL antigens ,PROSTATE diseases ,PROSTATITIS ,DRUG administration - Abstract
This paper describes the histopathology of chronic tuberculin-type hypersensitivity reactions in the normal canine and malignant human prostate. Seven dogs were sensitized by injection of Freund's complete adjuvant and the histological response to the subsequent intra-prostatic injection of 6 mg tuberculin PPD was documented. A chronic mononuclear cell prostatitis persisted for 4 weeks and was accompanied by paracortical distension and follicular hyperplasia in regional lymph nodes. Six patients with carcinoma of the prostate were given multiple intra-prostatic injections of BCG, which induced a chronic mononuclear cell prostatitis with some evidence of tumour-cell necrosis. The study indicated that the prostate can support chronic cell-mediated allergic reactions to extrinsic antigens and that intra-prostatic injections of BCG can be administered without harmful ejects to patients with malignant prostatic disease. [ABSTRACT FROM AUTHOR]
- Published
- 1976
26. AUGMENTATION OF LYMPHOCYTE TRANSFORMATION TO TUBERCULIN PPD.
- Author
-
Hamblin, Anne S., Maini, R. N., and Dumonde, D. C.
- Subjects
LYMPHOCYTES ,TUBERCULIN ,IMMUNE response ,DNA ,LEUCOCYTES ,IMMUNOLOGY - Abstract
There is recent interest in whether dialysable transfer factor can specifically increase immune responses when added to lymphoid cells in vitro. This report demonstrates that transfer factor preparations (human leucocyte dialysates) 'augment' rather than 'transfer' lymphocyte transformation responses (DNA synthesis) to tuberculin PPD in vitro and that the magnitude of this augmentation is proportional to the level of DNA synthesis induced by PPD in the absence of added transfer factor. Experiments showed that transfer factor preparations from Mantoux-positive or Mantoux-negative 'donors' were equally effective in augmenting 'recipient' lymphocyte trans- formation responses to PPD. Thus the extent of augmentation was related, not to the tuberculin sensitivity of the transfer factor donors, but to that of the recipients. In the absence of tuberculin PPD, transfer factor preparations sometimes stimulated lymphocyte DNA synthesis, but the extent of this was small and inconstant. The results therefore provide evidence for an antigen-dependent, but not an antigen- specific effect of transfer factor in increasing lymphocyte DNA synthesis in vitro. It is suggested that leucocyte dialysates contain an augmenting factor which may facilitate the response of antigen-sensitive cells to PPD in vitro, or may facilitate the recruitment into DNA synthesis of cell populations responding to mitogenic lymphokine produced during lymphocyte transformation. [ABSTRACT FROM AUTHOR]
- Published
- 1976
27. ACCELERATED CYTODIFFERENTIATION OF ANTIBODY-SECRETING CELLS IN GUINEA-PIG LYMPH NODES STIMULATED BY SHEEP ERYTHROCYTES AND LYMPHOKINES.
- Author
-
Kelly, R. H., Susan Harvey, V., Sadler, Tessa E., and Dumonde, D. C.
- Subjects
IMMUNOGLOBULINS ,CELLS ,ERYTHROCYTES ,LYMPHOKINES ,LYMPH nodes ,IMMUNIZATION - Abstract
Lymphokines. produced in response to structurally unrelated antigens. altered the course of a primary anti-sheep erythrocyte plaque-forming cell response within the regional lymph nodes of normal guinea-pigs. Intralymphatic injection of a small dose of lymphokines (05 8 μg) 1 day after antigen priming accelerated the rate of indirect plaque-forming cell cytodifferentiation between the 5th and the 9th days of the response. This effect was lint related to changes in the level of antigen trapping by lymph node macrophages. but the lymphocyte mitogenic activity may have been important for the response since there was a significant increase in [³H]thymidine incorporation within the lymphokine-treated nodes on the 3rd day following immunization. [ABSTRACT FROM AUTHOR]
- Published
- 1975
28. EXPERIMENTAL CUTANEOUS LEISHMANIASIS IV. SELECTIVE SUPPRESSION OF CELL-MEDIATED IMMUNITY DURING THE RESPONSE OF GUINEA-PIGS TO INFECTION WITH LEISHMANIA ENRIETTII.
- Author
-
Bryceson, A. D. M., Bray, R. S., and Dumonde, D. C.
- Subjects
CELLULAR immunity ,PROTOZOAN diseases ,LEISHMANIASIS ,IMMUNOGLOBULINS ,METASTASIS ,IMMUNE response - Abstract
The purpose of this study was to determine whether suppression of acquired. cell-mediated immunity occurred during the course of cutaneous leishmaniasis of the guinea-pig. In order to do this, groups of animals were infected with amastigotes of Leishmania enriettii in doses ranging from 10
1 to 2 × 108 organisms. The clinical course of primary and metastatic infection was followed for up to 30 weeks and the immunological response was examined by skin tests of hypersensitivity to soluble leishmanial antigens. by detection of circulating antibody, and by determining the resistance of animals to reinfection with fresh organisms. With increasing inoculum size the incubation period (for the establishment of a primary lesion) diminished from 4 weeks (101 organisms) to 1 week (2 × 108 organisms). Large inocula (2 × 108 ) led to large ulcerated primary lesions with widespread metastases and death of sonic animals in the group. But no evidence of visceralization. With increasing dose of organisms, there was increasingly rapid development of delayed hypersensitivity and of antibody as detected by immunofluorescence: thus there was no evidence that high inocula produced immunological tolerance. With inocula > 105 , a characteristic and selective depression of delayed hypersensitivity occurred when primary lesions were well developed and when metastatic infection was well advanced. Surviving animals recovered their delayed hypersensitivity as primary and metastatic lesions healed. After healing of the primary lesions, animals in all groups were fully resistant to reinfection, even though some of them bore persistent metastases. It was concluded that the immunosuppressive effects of heavy infecting inocula were due to desensitization of rapidly acquired, cell-mediated immunity rather than to the induction of immunological tolerance. It is suggested that this mechanism might underlie certain features of disseminated leishmaniasis in man. [ABSTRACT FROM AUTHOR]- Published
- 1974
29. Rapid cytokine up-regulation of integrins, complement receptor 1 and HLA-DR on monocytes but not on lymphocytes.
- Author
-
Limb, G. A., Hamblin, A. S., Wolstencroft, R. A., and Dumonde, D. C.
- Subjects
IMMUNITY ,LYMPHOCYTES ,ANTIVIRAL agents ,INTERFERONS ,INTEGRINS ,IMMUNOGLOBULINS - Abstract
Short-term (3 hr) incubation of whole blood with human recombinant cytokines induced rapid changes in the expression of monocyte but not of lymphocyte surface molecules. The percentage of monocytes bearing CD11b molecules was enhanced by tumour necrosis factor-beta (TNF-α), whilst that of CD11c was increased by both TNF-α and TNF-β. The mean fluorescence intensity (MFI) of monocyte CD11a was enhanced by interleukin-2 (IL-2), TNF-α and TNF-β, and that of CD11b. CD11c and CD18 was increased by IL-2, IL-4, TNF-α and TNF-β. The proportion of monocytes expressing HLA-DR antigens was not modified by the cytokines investigated, but its MFI was increased by IL-2, IL-4, TNF-α and TNF-β. In contrast, the percentage of monocytes bearing complement receptor 1 (CD35) was enhanced by IL-2, TNF-α and TNF-β but the MFI of this molecule was not modified by these cytokines. The highest up-regulation of CD18, HLA-DR and CD35 was observed with 100 U/ml of either IL-2. IL-4, TNF-α or TNF-β. Decreasing the concentration of all four cytokines from 100 to 10 and 1 U/ml diminished the levels of expression of all molecules, with the exception of CD35, which reached its maximum upon incubation with I U/ml of TNF-α. IL-1β, IL-6 or interferon-gamma (IFN-γ) did not modify the expression of any of the above monocyte surface determinants. Moreover, none of the lymphocyte surface molecules investigated was modified by 3-hr incubation of blood with cytokines. The demonstration that cytokines selectively and rapidly up-regulate integrins, complement receptor 1 and HLA-DR molecules, on monocytes but not on lymphocytes, suggests that similar mechanisms of mononuclear cell activation by cytokines may control the development and duration of the inflammatory process. [ABSTRACT FROM AUTHOR]
- Published
- 1992
30. Selective up-regulation of human granulocyte integrins and complement receptor 1 by cytokines.
- Author
-
Limb, C. A., Hamblin, A. S., Wolstencroft, R. A., and Dumonde, D. C.
- Subjects
GRANULOCYTES ,INTEGRINS ,CELL receptors ,INTERLEUKINS ,TUMOR necrosis factors ,CYTOKINES - Abstract
The percentage of human granulocytes expressing the integrins CD11b and CD11c as well as complement receptor 1 (CD35) was increased by short-term incubation of whole blood with interleukin-2 (IL-2), interleukin-4 (IL-4) and tumour necrosis factors alpha and beta (TNF-α and TNF-β). The mean fluorescence intensity of granulocyte CD18 was also increased by the above cytokines, whilst that of CD11b was only increased by TNF-β. Up-regulation of granulocyte CD18 expression was seen with 1 U/ml of IL-2, TNF-α or TNF-β, in contrast to the effect of IL-4 which was only observed with 100 U/ml. Similarly, enhanced expression of CD35 was induced by 1 U/ml of lL-2 or TNF-α but not by concentrations of IL-4 or TNF-β lower than 100 U/ml. Cytokine effects on the CD11/CD18 complex and CD35 molecules were not modified by cycloheximide, suggesting that their increased expression was not due simply to synthesis de novo. None of the granulocyte surface determinants investigated was altered upon short-term incubation of blood with either IL-1, IL-6 or interferon-gamma (IFN-γ). The demonstration in vitro that cytokines selectively up-regulate granulocyte integrins and complement receptor 1, suggests that similar mechanisms may be operating during the control of granulocyte-mediated inflammatory processes. [ABSTRACT FROM AUTHOR]
- Published
- 1991
31. Antigenicity and uveitogenicity of partially purified peptides of a retinal autoantigen, S-antigen.
- Author
-
Banga, J. P., Kasp, E., Ellis, B. A., Brown, E., Suleyman, S., and Dumonde, D. C.
- Subjects
MOLECULAR biology ,MOLECULAR immunology ,IMMUNOLOGY ,PEPTIDES ,IMMUNOBLOTTING ,ANTIGEN analysis - Abstract
S-antigen, a potent retinal autoantigen involved in human inflammatory eye disease, has been chemically digested with cyanogen bromide to generate various peptide fragments. Cleavage of bovine S-antigen at methionyl residues generates seven major polypeptide fragments of apparent molecular weight 26,000, 22,000, 19,000, 18,000, 12,500, 8000 and 3000, respectively. Immunoblotting following SDS-polyacrylamide gel electrophoresis either with monoclonal antibodies known to be directed to two separate antigenic determinants on S-antigen or with various polyclonal antisera identified two peptide fragments of 26,000 and 18,000 MW. The extreme insolubility of the larger peptide fragments in aqueous or organic buffers makes the purification of the polypeptides by biochemical procedures difficult. However partial purification of the remaining soluble peptides by gel filtration in urea containing buffers made it possible to ascertain that the 18,000 MW peptide is an important constituent that carries a uveitogenic determinant of this autoantigen. [ABSTRACT FROM AUTHOR]
- Published
- 1987
32. Numerical immunotaxonomy of <em>Leishmania</em> I. DIFFERENTIATION OF FOUR STRAINS OF <em>LEISHMANIA</em> BY SEROLOGICAL TESTS.
- Author
-
Matossian-Rogers, A., Lumsden, W. H. R., and Dumonde, D. C.
- Subjects
LEISHMANIA ,IMMUNOCYTOCHEMISTRY ,PARASITES ,IMMUNITY ,BLOOD plasma ,IMMUNE serums - Abstract
This paper describes the application of numerical methods to the arrangement of four leishmanial strains according to their reactivity and cross-reactivity in tests of parasite agglutination, indirect immunofluorescence and passive cutaneous anaphylaxis with antisera prepared by immunization or infection of rabbits, guinea-pigs and mice. Using corresponding pools of animal sera as test 'reagents' the antigenic reactivity of the four leishmanial strains (L. enriettii, L. tropica major, L. aethiopica and L. mexicana amazonensis) was scaled by reference to end point serum titres; and antigenic relationships between individual strain pairs were expressed as mean similarity coefficients, giving equal weight to the results of the different serological tests. Overall analysis of the results revealed that L. mexicana amazonensis and L. tropica major were the two most closely related strains, clustering with an overall similarity coefficient of 89 per cent, whereas coefficients of similarity between other strain combinations fell between 75 and 80 per cent. Although different sera had different discriminatory capacity for the leishmanial strains, two combinations of serum reagent and test system yielded relationships between the four strains that most closely approximated to the overall values. These were: (a) immunofluorescence tests with mouse antisera; and (b) agglutination tests with selected rabbit antisera. The results illustrate the use of a number of immunological parameters in relatingmicro organisms of a given genus, and reveal a serological classification of the four leishmanial strains at variance with their geographical origin. [ABSTRACT FROM AUTHOR]
- Published
- 1976
33. ROLE OF LYMPHOCYTE ACTIVATION PRODUCTS (LAP) IN CELL-MEDIATED IMMUNITY I. PREPARATION AND PARTIAL PURIFICATION OF GUINEA-PIG LAP.
- Author
-
Dumonde, D. C., Page, D. A., Matthew, Margaret, and Wolstencroft, R. A.
- Subjects
- *
LYMPHOKINES , *CELLULAR immunity , *CHROMATOGRAPHIC analysis , *ANTIGENS , *BLOOD proteins , *MACROPHAGES - Abstract
Partial purification of soluble products of guinea-pig lymphocyte activation (LAP) was undertaken by fractional precipitation with ammonium sulphate, ion-exchange and Sephadex chromatography, and by immune precipitation of inducing antigen and of contaminating serum protein. During these purification steps the activity of macrophage migration-inhibition factor (MIF) was concentrated up to 1300-fold and separated from inducing antigen and serum protein. An endpoint assay was devised for expressing antigen-induced MIF activity of LAP fractions as weights of material giving 30% inhibition of migration (MI30 doses). MIF activity precipitated between 50% and 80% saturated ammonium sulphate and eluted from DEAE-cellulose at pH 7-9 at intermediate salt concentrations (0-03-0-2 M phosphate). On Sephadex gel filtration MIF activity was concentrated in fractions of molecular weight range 56,000-82,000 with a smaller amount of activity eluting from 20,000-56,000. After immune precipitation of extraneous protein and elution from DEAE-cellulose, LAP material was found to have an MI30 dose of 0-4 /μg. Materials representative of antigen and serum protein-depleted MIF were selected for intralymphatic injection in order to determine whether MIF-rich LAP fractions were able to induce paracortical distension in guinea-pig lymph nodes (see following paper). [ABSTRACT FROM AUTHOR]
- Published
- 1972
34. THE PRODUCTION OF LYMPHOCYTE MITOGENIC FACTOR AND MIGRATION-INHIBITION FACTOR BY ANTIGEN-STIMULATED LYMPHOCYTES OF SUBJECTS WITH GRASS POLLEN ALLERGY.
- Author
-
Maini, R. N., Dumonde, D. C., Faux, J. A., Hargreave, F. E., and Pepys, J.
- Subjects
- *
ALLERGIES , *INTERLEUKIN-2 , *ANTIGENS , *THYMIDINE , *LYMPHOCYTES , *MACROPHAGES - Abstract
Peripheral blood lymphocytes of twenty-three subjects with grass pollen allergy were cultured with grass pollen antigen for 3 days. After harvesting, the culture supernatants were added to fresh autologous lymphocytes which were maintained in culture for 6 days. Cellular uptake of [³H]thymidine was measured during the sixth day of culture, and revealed that the lymphocyte culture supernatants stimulated greater thymidine uptake than expected from the lymphocyte transformation response to corresponding amounts of antigen. The supernatant factor which mediated this effect was termed `lymphocyte mitogenic factor' by analogy with a similar response of lymphocytes in clinical and experimental delayed hypersensitivity. Lymphocyte culture supernatants were also tested for migration- inhibition factor by their ability to inhibit the migration of guinea-pig macrophages. [ABSTRACT FROM AUTHOR]
- Published
- 1971
35. The Effects of Antibodies on Cells III. STUDIES ON THE INTERACTION OF RAT LIVER MITOCHONDRIA AND LYSOSOMES WITH ANTIBODY AND COMPLEMENT.
- Author
-
Dumonde, D. C., Roodyn, D. B., and Prose, P. H.
- Subjects
- *
FERRITIN , *AUTOANTIBODIES , *MITOCHONDRIA , *LYSOSOMES , *PRECIPITIN reaction , *IMMUNITY - Abstract
Complement-fixing and precipitating antibodies to mitochondrial and lysosomal fractions of rat liver were induced in rabbits. The incubation of these subcellular fractions with ferritin-labelled antibody revealed localization of the antibody on mitochondria and lysosomes, but no specific morphological effect of antibody and complement. Incubation of the cell fractions with antibody and complement did not impair the efficiency of mitochondrial oxidative phosphorylation or affect the latency and sedimentation characteristics of lysosomal acid phosphatase. The results are discussed in relation to the action of antibody and complement on cells and to possible mechanisms of tissue damage in autoimmunity. [ABSTRACT FROM AUTHOR]
- Published
- 1965
36. The Effects of Antibodies on Cells II. CHANGES IN THE ELECTROPHORETIC MOBILITY OF ASCITES TUMOUR CELLS TREATED WITH ANTIBODIES AND COMPLEMENT.
- Author
-
Forrester, J. A., Dumonde, D. C., and Ambrose, E. J.
- Subjects
- *
IMMUNOGLOBULINS , *CELLS , *ASCITES tumors , *CANCER cells , *ELECTROPHORESIS , *ELECTROCHEMISTRY - Abstract
This communication describes the use of micro-electrophoresis in studying the changes in ascites tumour cells exposed to antibodies and complement. Treatment of the cells with rabbit antibody led to a change in electrophoretic mobility consistent with a surface adsorption of γ-globulin. The addition of complement led to a reduction in this electrophoretic effect of antibody. Treatment of the cells with neuraminidase, which produced a marked fall in their electrophoretic mobility, did not alter the effect of rabbit antibody and complement on the cells. Incubation with iso-antibody, in the presence or absence of complement, did not alter the mobility of the ascites cells measured at pH 7.0. The addition of 0.01 M calcium chloride to the electrophoresis medium produced a fall in mobility of the cells exposed to either antibody preparation in the presence of complement. Therefore, although iso-antibody and complement did not produce direct changes in cell mobility, changes in the cell surface could be detected by electrophoresis in the presence of calcium ions. The possibility is discussed that, during immune cytolysis, unmasking of phosphate groups of phospholipids might take place in the cell surface. [ABSTRACT FROM AUTHOR]
- Published
- 1965
37. Autoantibody Production in Rabbits V. COMPARISON OF THE AUTOANTIBODY RESPONSE AFTER THE INJECTION OF RAT AND RABBIT LIVER AND BRAIN.
- Author
-
Asherson, G. L. and Dumonde, D. C.
- Subjects
- *
AUTOANTIBODIES , *RABBITS , *INJECTIONS , *IMMUNOGLOBULINS , *LABORATORY animals - Abstract
The injection of rat liver and rat brain in Freund's complete adjuvant into rabbits led to the production of complement fixing autoantibodies against rabbit tissue. The autoantibody response following the injection of rabbit liver and brain was much smaller. The autoantibody response to rat liver occurred even when Freund's incomplete adjuvant was used. The injection of rabbit liver in Freund's complete adjuvant into rabbits which had produced autoantibody after the injection of rat liver did not increase the level of autoantibody to rabbit liver. In most, but not all, rabbits the natural antibody found in the sera taken before immunization was destroyed by heating the sera at 65°. After immunization with rat liver in Freund's complete adjuvant the levels of serum antibody to rabbit liver stable at 56° rose by day 5; however, autoantibody stable at 65° was not detectable until between days 7 and 14. [ABSTRACT FROM AUTHOR]
- Published
- 1964
38. EXPERIMENTAL CUTANEOUS LEISHMANIASIS III EFFECTS OF THYMECTOMY ON THE COURSE OF INFECTION OF CBA MICE WITH <em>LEISHMANIA TROPICA</em>.
- Author
-
Preston, Patricia M., Carter, R. L., Leuchars, Elizabeth, Davies, A. J. S., and Dumonde, D. C.
- Subjects
IMMUNOGLOBULINS ,LYMPH nodes ,PROTOZOAN diseases ,ENDOCRINE glands ,LYMPHOID tissue ,CELLULAR immunity ,FLUORESCENCE ,IMMUNOCYTOCHEMISTRY ,IMMUNOFLUORESCENCE - Abstract
This paper describes the course of infection and the immunological response in thymus-deprived and normal CBA mice after intradermal inoculation with promastigotes of L. tropica. Infection of normal mice resulted in the development of a cutaneous ulcer healing within 12 weeks. As the infection progressed and the draining lymph nodes increased in weight, changes in the paracortical and follicular regions were accompanied by the development of delayed hypersensitivity and the production of antibodies detectable by immunofluorescence and a parasite agglutination test. Lesions in thymectomized irradiated mice healed more slowly and the draining lymph nodes were smaller than in normal mice. Follicular reactions were feeble and paracortical activity depressed. The most noticeable feature of these lymph nodes was a persistent and intense macrophage infiltration. Delayed hypersensitivity and antibodies detectable by immunofluorescence were correspondingly low; but parasite agglutinating antibody was not depressed. The course of infection and immunological response of a control group of sham thymectomized, irradiated mice resembled that of normal mice. These experiments indicate that thymus-dependent cell populations play an important role in the response of mice to infection with L. tropica. [ABSTRACT FROM AUTHOR]
- Published
- 1972
39. EXPERIMENTAL CUTANEOUS LEISHMANIASIS II. EFFECTS OF IMMUNOSUPPRESSION AND ANTIGENIC COMPETITION ON THE COURSE OF INFECTION WITH <em>LEISHMANIA ENRIETTII</em> IN THE GUINEA-PIG.
- Author
-
Bryceson, A. D. M., Preston, Patricia M., Bray, R. S., and Dumonde, D. C.
- Subjects
PROTOZOAN diseases ,PROSTATE-specific antigen ,INJECTIONS ,IMMUNOREGULATION ,LEISHMANIASIS ,IMMUNOLOGICAL adjuvants - Abstract
Intradermal inoculation of the guinea-pig with Leishmania enriettii results in a self-healing cutaneous lesion which provides a laboratory model of human cutaneous leishmaniasis and which is dominated by cell-mediated immunological responses (Bryceson et al, 1970). In this study we sought to design experimental situations resembling non-healing forms of cutaneous leishmaniasis in man and to determine whether these experimental situations were accompanied by abnormalities in the immunological response to infection. This paper describes three procedures which impair the resistance of guinea-pigs to leishmanial infection: (i) induction of partial immunological tolerance to leishmanial antigen; (ii) systemic injection of anti-lymphocyte serum (ALS); and (iii) regional antigenic competition produced by multiple injections of bacterial adjuvants. Injection of soluble leishmanial antigen (PSA) during the third week of foetal life suppressed resistance to neonatal infection with L. enriettii; local infections were severe and were accompanied by metastatic spread and by impaired development of delayed hypersensitivity (DH). Injection of PSA into the 6-week foetus and into the adult guinea-pig led to impaired DH after leishmanial infection, but resistance to infection was only slightly suppressed. Transient impairment of DH was induced by a short injection course of adult animals with ALS during the first 3 weeks of infection, which resulted in large primary lesions with temporary metastatic spread. Multiple regional injections of tubercle- and corynebacterial-adjuvant emulsions markedly suppressed resistance to subsequent leishmanial infection; large ulcerative lesions were accompanied by widespread nodular metastases, the unusual appearance of haemagglutinating antibody, and death of some animals. [ABSTRACT FROM AUTHOR]
- Published
- 1972
40. “Lymphokines”: Non-Antibody Mediators of Cellular Immunity generated by Lymphocyte Activation
- Author
-
DUMONDE, D. C., WOLSTENCROFT, R. A., PANAYI, G. S., MATTHEW, MARGARET, MORLEY, J., and HOWSON, W. T.
- Abstract
Four principal features of cellular immunity in the guinea-pig are mediated by a group of soluble factors generated by antigen-activated lymphocytes. These “lymphokines” are different from classical antibodies.
- Published
- 1969
- Full Text
- View/download PDF
41. Human transfer factor in vitro. I. Augmentation of lymphocyte transformation to tuberculin PPD
- Author
-
Hamblin, Anne S., Maini, R. N., and Dumonde, D. C.
- Subjects
Articles - Abstract
There is recent interest in whether dialysable transfer factor can specifically increase immune responses when added to lymphoid cells in vitro. This report demonstrates that transfer factor preparations (human leucocyte dialysates) `augment' rather than `transfer' lymphocyte transformation responses (DNA synthesis) to tuberculin PPD in vitro and that the magnitude of this augmentation is proportional to the level of DNA synthesis induced by PPD in the absence of added transfer factor. Experiments showed that transfer factor preparations from Mantoux-positive or Mantoux-negative `donors' were equally effective in augmenting `recipient' lymphocyte transformation responses to PPD. Thus the extent of augmentation was related, not to the tuberculin sensitivity of the transfer factor donors, but to that of the recipients. In the absence of tuberculin PPD, transfer factor preparations sometimes stimulated lymphocyte DNA synthesis, but the extent of this was small and inconstant. The results therefore provide evidence for an antigen-dependent, but not an antigen-specific effect of transfer factor in increasing lymphocyte DNA synthesis in vitro. It is suggested that leucocyte dialysates contain an augmenting factor which may facilitate the response of antigen-sensitive cells to PPD in vitro, or may facilitate the recruitment into DNA synthesis of cell populations responding to mitogenic lymphokine produced during lymphocyte transformation.
- Published
- 1976
42. Leucocyte chemotactic activity in the parallel bioassay of guinea--pig lymphokines
- Author
-
DeFranco, M F, Hanson, J M, Morley, J, Wolstencroft, R A, and Dumonde, D C
- Subjects
Inflammation ,Chemotaxis, Leukocyte ,Lymphokines ,Macrophages ,Cell Migration Inhibition ,Guinea Pigs ,Dose-Response Relationship, Immunologic ,Animals ,Ascitic Fluid ,Biological Assay ,Mitogens ,Lymphocyte Activation ,Research Article - Abstract
This paper describes the application of parallel bioassay to determine the extent to which the leucocyte chemotactic activity of guinea-pig lymphokine preparations is associated with their lymphocyte mitogenic, inflammatory (increased vascular permeability) and macrophage migration inhibitory activities. A convenient test of chemotactic activity was devised whereby Coulter counter determinations were made of the number of peritoneal exudate cells passing through a Nuclepore membrane into the medium of the lower (test) compartment of a chemotaxis chamber. Symmetrical parallel line (2+2) dose assays were used to obtain potency ratio estimates of the chemotactic activity of seven lymphokine preparations whose mitogenic, inflammatory and migration inhibitory activities were already known. Statistical analysis of the results revealed a clear dissociation of chemotactic activity from mitogenic and migration inhibitory activities; but with six of the seven lymphokine preparations, a marked similarity was revealed between their chemotactic and inflammatory activities. Cytological studies showed that although the lymphokine preparations were chemotactic for different cell types, there was a preferential migration of neutrophils and the smaller mononuclear cells. The demonstration by parallel bioassay of an association between the ability of lymphokine preparations to increase vascular permeability in vivo and to promote chemotaxis of leucocytes in vitro is viewed in relation to the possible role of lymphokine in inflammatory processes.
- Published
- 1977
43. Accelerated cytodifferentiation of antibody-secreting cells in guinea-pig lymph nodes stimulated by sheep erythrocytes and lymphokines
- Author
-
Kelly, R H, Harvey, V S, Sadler, T E, and Dumonde, D C
- Subjects
Lymphokines ,Erythrocytes ,Sheep ,Time Factors ,Macrophages ,Guinea Pigs ,Injections, Intralymphatic ,Hemolytic Plaque Technique ,Lymphocyte Activation ,Tritium ,Endotoxins ,Hemocyanins ,Animals ,Autoradiography ,Lymph Nodes ,gamma-Globulins ,Antibody-Producing Cells ,Immunization Schedule ,Research Article ,Thymidine - Abstract
Lymphokines, produced in response to structurally unrelated antigens, altered the course of a primary anti-sheep erythrocyte plaque-forming cell response within the regional lymph nodes of normal guinea-pigs. Intralymphatic injection of a small dose of lymphokines (0-5-8 mug) 1 day after antigen priming accelerated the rate of indirect plaque-forming cell cytodifferentiation between the 5th and the 9th days of the response. This effect was not related to changes in the level of antigen trapping by lymph node macrophages, but the lymphocyte mitogenic activity may have been important for the response since there was a significant increase in [3H]thymidine incorporation within the lymphokine-treated nodes on the 3rd day following immunization.
- Published
- 1975
44. Numerical immunotaxonomy of Leishmania. I. Differentiation of four strains of Leishmania by serological tests
- Author
-
Matossian-Rogers, A, Lumsden, W H, and Dumonde, D C
- Subjects
Leishmania ,Agglutination Tests ,Passive Cutaneous Anaphylaxis ,Animals ,Fluorescent Antibody Technique ,Serotyping ,Research Article - Abstract
This paper describes the application of numerical methods to the arrangement of four leishmanial strains according to their reactivity and cross-reactivity in tests of parasite agglutination, indirect immunofluorescence and passive cutaneous anaphylaxis with antisera prepared by immunization or infection of rabbits, guinea-pigs and mice. Using corresponding pools of animal sera as test 'reagents' the antigenic reactivity of the four leishmanial strains (L. enriettii, L. tropica major, L. aethiopica and L. mexicana amazonensis) was scaled by reference to end-point serum titres; and antigenic relationships between individual strain pairs were expressed as mean similarity coefficients, giving equal weight to the results of the different serological tests. Overall analysis of the results revealed that L. mexicana amazonensis and L. tropica major were the two most closely related strains, clustering with an overall similarity coefficient of 89%, whereas coefficients of similarity between other strain combinations fell between 75 and 80%. Although different sera had different discriminatory capacity for the leishmanial strains, two combinations of serum reagent and test system yielded relationships between the four strains that most closely approximated to the overall values. These were: (a) immunofluorescence tests with mouse antisera; and (b) agglutination tests with selected rabbit antisera. The results illustrate the use of a number of immunological parameters in relating micro-organisms of a given genus, and reveal a serological classification of the four leishmanial strains at variance with their geographical origin.
- Published
- 1976
45. Experimental cutaneous leishmaniasis. V. Protective immunity in subclinical and self-healing infection in the mouse
- Author
-
Preston, P M and Dumonde, D C
- Subjects
Hypersensitivity, Immediate ,Male ,Immunity, Cellular ,Time Factors ,Immunization, Passive ,biochemical phenomena, metabolism, and nutrition ,Disease Models, Animal ,Mice ,Immunoglobulin M ,Immunoglobulin G ,Antibody Formation ,Mice, Inbred CBA ,Animals ,Hypersensitivity, Delayed ,Immunization ,Leishmaniasis ,Research Article - Abstract
This study shows how infection of CBA mice with L. tropica can be manipulated so as to mimic the principal features of both subclinical and self-healing cutaneous leishmaniasis in man. CBA mice were infected with graded inocula of L. tropica promastigotes. The pattern of primary infection was found to be dependent on dose of infecting organisms: mice given low dose inocula (10(2), 10(3)) developed subclinical infections; those given high dose inocula (10(4), 10(5), 10(6)) developed overt, clinical lesions. Size and duration of lesions, and antibody production were directly proportional to dose; delayed hypersensitivity responses were inversely proportional to dose. Protective immunity to challenge infection was induced by both subclinical and clinical infection; and was manifest both during and after the healing stages of primary lesions. Protective immunity was also induced by artificial immunization with sonicated promastigotes in adjuvants but was only manifest if the challenge dose was not too large. The course of challenge infections differed depending on the method of immunization, i.e. whether by infection or artificial immunization. Lymphoid cells from immune CBA mice conferred protection on recipient syngeneic CBA mice against challenge infection; serum from immune mice did not, but suspension of immune peritoneal cells in immune serum enhanced their protective capacity. The experimental induction of protective immunity by low-dose infection, without a clinical allergic response at the site of inoculation, is of importance in designing an immunoprophylactic approach to human leishmaniasis.
- Published
- 1976
46. Lupus Erythematosus: A Review of the Current State of Discoid and Systemic Lupus Erythematosus and their Variants: Second edition
- Author
-
Dumonde, D. C.
- Subjects
Book Review - Published
- 1975
47. Heat-induced aggregated human IgG modifies the adherence of human polymorphonuclear cells to cultured endothelium
- Author
-
Brown, K A, McCarthy, D, Bull, M, Chasty, R C, and Dumonde, D C
- Subjects
Hot Temperature ,Neutrophils ,Immunoglobulin G ,Cell Adhesion ,Humans ,Antigen-Antibody Complex ,Endothelium, Vascular ,Cells, Cultured ,Research Article - Abstract
The adherence of human blood polymorphonuclear cells (PMNC) to cultured porcine aortic endothelium was enhanced by high concentrations of heat-stable IgG aggregates (HAGG) when sera was omitted from the culture media. With 20% human serum present in the media, HAGG induced a dose-related inhibition of PMNC adhesions with concentrations as low as 10 micrograms/ml producing a significant effect. This inhibitory action of HAGG, which was optimally expressed after 30 min of incubation, seemed to be directed at the PMNC rather than the endothelium. Heat-inactivation of the sera resulted in a marked decline of the inhibitory activity of HAGG. Aggregates of size 15-21 s were demonstrated to be most effective in inhibiting PMNC attachment and it is complexes of this size which are commonly found in the circulation of patients with chronic inflammatory diseases. Immune complex modification of PMNC adherence may control leucocyte extravasation during inflammation.
- Published
- 1989
48. Production of prostaglandins by porcine endothelial cells in culture [proceedings]
- Author
-
Dumonde, D C, Jose, P J, Page, D A, and Williams, T J
- Subjects
Swine ,Prostaglandins ,Animals ,Endothelium ,Aorta ,Cells, Cultured ,Research Article - Published
- 1977
49. Human transfer factor in vitro. II. Augmentation of lymphocyte transformation to phytohaemagglutinin
- Author
-
Hamblin, Anne S., Dumonde, D. C., and Maini, R. N.
- Subjects
chemical and pharmacologic phenomena ,Articles - Abstract
This paper describes experiments in which human peripheral blood lymphocyte transformation by phytohaemagglutinin (PHA) is augmented by the addition of human dialysable transfer factor. Dextran-separated peripheral blood leucocytes were cultured for 4 days with a range of PHA concentrations so as to produce low, moderate, high or very high incorporation of [3H]thymidine. When transfer factor preparations were added to the cultures, in concentrations similar to those augmenting lymphocyte transformation to tuberculin PPD, augmentation of PHA responses was observed in two-thirds of the experiments (25/38). In these experiments the extent of augmentation was proportional to the level of DNA synthesis induced by PHA in the absence of added transfer factor. It appears that preparations of transfer factor are able to augment lymphocyte transformation responses to PHA in vitro, but that this effect occurs with less regularity than does augmentation of lymphocyte transformation to tuberculin PPD.
- Published
- 1976
50. Interleukin 1 in Crohn's disease
- Author
-
Satsangi, J, Wolstencroft, R A, Cason, J, Ainley, C C, Dumonde, D C, and Thompson, R P
- Subjects
Adult ,Lipopolysaccharides ,Male ,Mice, Inbred C3H ,T-Lymphocytes ,Middle Aged ,Lymphocyte Activation ,Mice ,Crohn Disease ,Animals ,Humans ,Biological Assay ,Colitis, Ulcerative ,Female ,Research Article ,Interleukin-1 - Abstract
A number of the activities currently ascribed to the mediator interleukin 1 (IL-1) are relevant to chronic inflammatory bowel disease. Using the mouse thymocyte stimulation assay, lymphocyte-activating factor (LAF) activity was measured in plasma samples and supernatants from cultures of peripheral blood mononuclear cells from 16 patients with Crohn's disease, six with ulcerative colitis, and 10 healthy subjects. Results were compared with disease activity, drug therapy, granulocyte count, and plasma levels of zinc and C-reactive protein (CRP). Very low levels of LAF were detected in a few plasma samples from each of the subject groups. Mononuclear cells from healthy subjects produced LAF only when cultured with lipopolysaccharide, but stimulated cells from patients produced greater amounts. Moreover, cells from six patients with Crohn's disease, not receiving steroids, produced LAF spontaneously. Crohn's disease patients also had low plasma zinc but elevated levels of CRP and granulocytes. This enhanced production of LAF in vitro may reflect a primary cellular defect in Crohn's disease, or a secondary consequence of monocyte activation.
- Published
- 1987
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