Search

Ajax mice fed a diet with a reduced proportion of protein, cleared carbon more slowly, and produced less antibody of lower affinity, when immunized with human serum transferrin (HST) in saline than did normally fed controls. This finding is discussed in terms of the defective antibody response in protein-malnourished children, and the possible contribution such environmental factors may have on immunopathological and neoplastic effects of infection. [ABSTRACT FROM AUTHOR]

Macrophage function, as measured by carbon clearance, differs in different inbred strains. Low affinity (KR) antibody response to HST is associated either with poor carbon clearance, or slow recovery from carbon blockade by macrophages. Carbon blockade reduces KR, but not Abt, in mice with high carbon clearance and KR. Stilboestrol increases carbon clearance and KR in mice with slow clearance and low KR. The significance of these findings in pathogenesis and treatment of chronic soluble complex disease is discussed. [ABSTRACT FROM AUTHOR]

Human monocytes were infected in vitro with Leishmania tropica major (L. major) protnastigotes which transformed to intraecllular amastigotes, A spontaneous increase in iymphocytc proliferation occurred in mononuclcar cell cultures where the monocytes had been infected with L. major organisms. In addition, an apparent additive effect of lymphocyte proliferation was seen in cultures infected with L. major following phytohaemagglutinin stimulation. This effect was apparent after 3 days in culture and the amount of increase in response was dependent on the number of monocytes in the culture. The effect was also dependent on the number of parasites ingested by the monocytes. The presence of monocytes was essential for this effect, as no enhancement was observed with supernatants from infected cells. This enhanced effect of lymphocyte proliferation was observed predominantly in the B lymphocyte subpopulation. These findings may be of relevance in the immunopathogenesis of Leishmania infections. [ABSTRACT FROM AUTHOR]

IgE was isolated from a patient with the hyper IgE, recurrent infection syndrome by immunoadsorption on sepharose bound goat anti-human IgE. Addition of this IgE to a monolayer culture of human monocytes resulted in a dose-dependent increase in PGE2 secretion. The addition of F(ab')2 fraction of goat anti-human IgE in the presence of sub-stimulating doses of IgE markedly increased PGE2 secretion; whereas addition of F(ab')2 fragment of irrelevant goat IgG had no effect. Similar activation of monocytes which could be enhanced by anti IgE was observed in the presence of the patient's serum. No such effect was seen in the presence of normal human serum. These results indicate that IgE may activate human monocytes and induce PGE secretion. [ABSTRACT FROM AUTHOR]

Leishmania organisms are obligate intracellular parasites of mammalian mononuclear phagocytes in vivo. In order to study the interactions of these parasites and mononuclear phagocytes, we have used a model of infection of Leishmania major in human monocytes in vitro. The presence of intracellular parasites did not alter the normal secretion of lysozyme or result in increased secretion of prostaglandin E2(PGE2) or superoxide anion by the monocytes. Addition of concanavalin A (Con A), which binds to a specific membrane receptor, zymosan particles or endotoxin to infected monocyte monolayers, resulted in the expected increase in PGE: secretion. In addition, the production of superoxide by infected monocytes treated with phorbol myristate acetate was not different from control uninfected cultures. Despite this evidence of biochemical activation, neither endotoxin. zymosan nor Con A had any parasiticidal effect on the intracellular parasites. In contrast. Con A-induced lymphokines from human mononuclear cells resulted in an increased killing of the intracellular amastigotes. These studies have shown that the induction of leishmaniacidal capacity of human monocytes is dependent on the type of stimulus used to induce activation. [ABSTRACT FROM AUTHOR]

The secretion of PGE2 from monocytes of newly diagnosed patients with Hodgkin's disease (HD) was compared to that of patients in remission, who were not receiving either chemotherapy or radiotherapy, and normal controls. We found that monocyte monolayers of some patients, both newly diagnosed and those in remission, secreted markedly elevated ievelsof PGE2. The lymphocyte proliferative response to PHA was increased to a similar extent in both newly diagnosed patients and those in remission when cultured in the presence of indomethacin. PGE: concentrations in the medium of mononuclear cultures correlated with the lymphocyte proliferative response to PHA (P<005). However, no correlation of monocyte PGEi production with decreased E rosette forming lyrnphocytes. anergy or clinical stage could be demonstrated. We suggest that PGE2 secretion by monocytes is indicative of an "activated" state of these cells. It is, however, unlikely that PGE2 is the only molecular species responsible for the decreased cellular immune function in HD. "Activated" monocytes may be part of the immune response in this disease and may be responsible for the decreased cellular immunity. [ABSTRACT FROM AUTHOR]

The effects of concanavilin A (Con A)-induced lymphokines from human peripheral blood mononuclear cells, enriched helper and suppressor lymphocyte populations and recombinant interferon-gamma (IFN-gamma) on the ability of monocytes to promote killing of intracellular Leishmania major (L. major) amastigotes and to induce the production of hydrogen peroxide (H2O2) was examined. All these mitogen-induced supernatants contained active IFN-gamma. There were no differences in the ability of these supernatants or IFN-gamma to promote the monocyte killing of the L. major amastigotes or H2O2 production. An increase in H2O2 production by monocyte monolayers was observed following the addition of either of these supernatants or IFN-gamma alone. In addition, a marked increase in the production of H2O2 was observed following priming with either of these mitogen-induced supernatants or IFN-gamma and the addition of a second stimulus, phorbol myristate acetate (PM A). Monoclonal antibody to IFN-gamma abrogated the increase in production of H2O2 by all these mitogen-induced supernatants; however, this antibody only resulted in partial inhibition of the leishmaniacidal effect of these lymphokines on human monocytes. These results would suggest that IFN-gamma is the component of the lymphokine that is largely or exclusively responsible for H2O2 production, while other factors in addition to IFN-gamma are important in promoting oxygen-independent mechanisms for the killing of intracellular L. major amastigotes. [ABSTRACT FROM AUTHOR]

Human monocytes suppressed both the phytohaemagglutin (PHA) or antigen-induced lymphocyte proliferative response, when the monocyte: lymphocyte ratio was increased or when the monocytes were stimulated with zymosan or endotoxin. The effect of monocytes on autologous lymphocyte proliferation was compared with that of macrophages obtained by culturing monocytes in vitro for 7 days. The lymphocyte proliferative responses were increased in the presence of macrophages, however, neither increasing their number nor stimulation by zymosan or endotoxin altered the autologous lymphocyte proliferative response to PHA or purified protein derivative (PPD). The PGE2 concentration in the medium of both the cultured monocytes or macrophages activated by zymosan and endotoxin rose markedly without a corresponding suppressor effect on lymphocyte proliferation in the presence of macrophages in the culture. Thus it seems that while PGE2 is a useful marker of mononuclear phagocyte activation, other molecular species are of importance in determining the lymphocyte proliferative response to mitogens and antigens. [ABSTRACT FROM AUTHOR]

Exposure of human monocytes in monolayer culture to concanavalin A (Con A) or Fc fragments of IgG results in decreased levels of lysozyme, acid phosphatase and the second component of complement (C2), but increased levels of prostaglandin E2 (PGE2) in the culture medium. Indomethacin blocked the effect of Con A and Fc fragments on PGE2 levels but did not alter the effects on the other secretory products. The addition of Con A to the monocyte cultures resulted in increased cAMP levels in short (< 20 min) and in long term incubations (24 hr). Long term exposure to the Fc fragments of IgG also resulted in elevated levels of cAMP. In long term cultures, elevation of cAMP levels by Fc fragments and Con A may in part be mediated by stimulation of endogenous prostaglandin production, since addition of indomethacin resulted in a return of cAMP towards basal levels. The addition of D-L isoproterenol, IBMX, or exogenous PGE2, reagents that increase cAMP content, or addition of Dibutyryl 3′, 5′ adenosine monophosphate (DBcAMP) to cultures resulted in a dose-dependent inhibition of secretion of acid phosphatase, lysozyme and C2. These findings suggest that certain secretory responses of human monocytes are reduced by agents which increase cAMP levels. These changes may be related to direct effects on adenylate cyclase stimulation or indirect effects on the release of other products which effect cAMP generation. These changes in cAMP content may in part be responsible for the reduced secretory response. [ABSTRACT FROM AUTHOR]

Human monocytes were maintained in tissue culture and the effect of various stimuli on their morphology and capacity to synthesize and secrete total protein, lysozyme, acid phosphatase, prostaglandin E and the second component of complement were determined. Human monomeric IgG, Fab fragments and albumin had no effect on the secretion of these products. However, addition of Fc fragments significantly decreased the synthesis of both lysosomal enzymes and the second component of complement and increased production of prostaglandin E. The addition of Con A to the monocyte monolayers resulted in a similar response. Latex particles slightly increased the secretion of acid phosphatase and C2, but had no effect on lysozyme secretion. Fc fragments also stimulated protein synthesis by monocyte monolayers cultured in serum-free medium. These ‘activators’ and endotoxin- or antigen-activated mononuclear cell supernatants (AMNS) resulted in varying degrees of increased spreading and adherence of the monocytes. The results of these studies suggest that the molecular species inducing the ‘activated state’ qualitatively and quantitatively determines the characteristics of the secretory response. [ABSTRACT FROM AUTHOR]

The binding of sensitized red cells to Fc receptors in human monocytes was studied by evaluating the effects of various pharmacological reagents and other treatments on EA rosette formation. Cytochalasin B and 2-deoxyglucose inhibited rosette formation in a dose-dependent manner. Sodium azide and incubation at 4° also inhibited rosette formation, while at 37° increased numbers of RBCs bound to the monocytes. The microtubular poisons, vinblastine and colchicine at high concentrations resulted in decreased adherence of monocytes and inhibition of rosette formation, while at low concentrations of colchicine, enhanced rosette formation was sometimes observed. Contrary to the effects on rosette formation, binding of [125I] IgG to monocyte monolayers was not altered by treatment of the monocytes with drugs. Magnesium ions were required to promote monocyte adherence, but both magnesium and calcium were needed for the best rosette formation. We conclude that the formation of EA rosettes is dependent not merely on binding of IgG to the Fc receptor but requires metabolically active monocytes, an intact cytostructure and suitable environmental conditions (temperature and cation concentration). [ABSTRACT FROM AUTHOR]

Humoral and cell-mediated responses to crude and purified parasite antigens were examined in patients with active cutaneous leishmaniasis caused by Leishmania major. The patients had serum antibody titres against parasite lysates ranging from 1/500 to 1/10 000 and recognized multiple components by Western blotting with molecular weights between 5000 and > 200 000. Several components, particularly at 5 and 50 kD, were recognized by most of the patients. The lymphoproliferative responses to two pure antigens, promastigote surface protease and lipophosphoglycan, both considered potential candidates for the development of a human vaccine were measured. No response to promastigote surface protease was observed even at 10 μg/ml; however, weak proliferation to lipophosphoglycan was consistently present. T cell blots examining peripheral blood lymphocyte proliferation, showed antigen-specific responses to a 72-82 kD component in promastigote lysates. [ABSTRACT FROM AUTHOR]

The deposition of complement in the kidney mesangium is a constant finding associated with renal injury in IgA nephropathy, even though IgA does not bind complement. We have previously reported that complement gene expression in the kidney increases concurrently with the progression of immune complex disease in murine lupus nephritis. We have now studied the expression of C3, C4, factor B and HLA-DRα mRNA by in situ hybridization in renal biopsy specimens of patients with IgA nephropathy and compared these findings to those in patients with other immune-mediated diseases of the kidney, hereditary nephritis and normal kidney. In IgA nephropathy, C3 and factor B mRNA were expressed in the renal tubular epithelial cells, while no expression of either C3 or factor B mRNA was apparent in the glomerulus. Specimens from patients with other immune-mediated forms of chronic glomerulonephritis also showed a similar pattern of expression of C3 and factor B mRNA only in the tubules, but not in the glomerules. However, C3 and factor B mRNA were not found in normal kidney tissue or biopsy specimens from patients with hereditary nephritis. C4 mRNA was expressed in the tubular epithelial cells in all specimens examined, indicating that C4 mRNA is constitutively expressed in the human kidney. In IgA nephropathy HLA-DRα mRNA was observed in the interstitium, but not the tubules or glomerular cells. In contrast, HLA-DRα mRNA was present in the glomerulus and scattered in the interstitium in other immune-mediated kidney diseases. There was no expression of HLA-DRα mRNA in hereditary nephritis or normal kidney. Our findings, which reflect the immunopathogenic events in vivo, provide new insights as to the interpretation of the molecular immunology of this immune complex disease. [ABSTRACT FROM AUTHOR]

We have studied the effect of IgA- and IgG-containing immune complexes on the production of complement proteins C3, factor B and C2 by human monocyte-derived macrophages, using biosynthetic labelling, immunoprecipitation, sodium dodecyl sulphate-polyacrylamide gel (SDS-PAGE) and autoradiography. There was a consistent increase in C3 production and secretion with both IgA and IgG immune complexes. This increase appeared after a 24-hr incubation period of the macrophages in the presence of immune complexes. No change in the biosynthesis of factor B and C2 proteins was observed in these experiments. Concomitant with the enhanced C3 biosynthesis, the immune complexes caused an increase in macrophage tumour necrosis factor (TNF) production; 310 + 24 U/ml/5 × 105 cells and 430 + 51 U/ml/5 × 105 cells for IgA and IgG immune complexes, respectively, venus 12 + 8 U/ml/5 × 105 cells in the control cells. The presence of prednisolone (2 × 10-5 M) or dexaniethasone (1 × 10-7 M) inhibited the immune complex-induced TNF production, but had no effect on C3-increased synthesis, suggesting that the effect of immune complexes was not mediated by endogenous TNF production. These findings may be relevant to the local inflammatory response in IgA immune complex-mediated diseases, including IgA nephropathy. [ABSTRACT FROM AUTHOR]

The clinical and laboratory findings of 35 children with familial Mediterranean fever who developed amyloidosis are described. The types, frequency, and severity of attacks of familial Mediterranean fever in these children were no different from patients with this disease without amyloidosis. Although amyloid was widely deposited in all tissues, the major clinical manifestations of the amyloidosis were proteinuria, the nephrotic syndrome, and progressive renal failure. Only 20% of the patients were alive 5 years after the first appearance of proteinuria. [ABSTRACT FROM AUTHOR]

Presents several medical case reports. Nature of idiopathic familial raised serum alkaline phosphatase activity; Plasma renin activity in the hypertension of the Guillain-Barre syndrome; assessment of high-density lipoprotein and other risk factors in coronary artery disease using angiography.

Unlabelled: A 4-y-old girl was admitted because of a left leg limp with an isolated swollen upper thigh and normal muscle enzymes. A radioisotope scan showed increased uptake especially in the bone and soft tissue of the left thigh, while magnetic resonance imaging of that region demonstrated widespread oedema in striated muscle. On muscle biopsy perivascular infiltrates were demonstrated but muscle fibres were not shown to be affected. Sequence analysis of reverse transcription-polymerase chain reaction amplified fragments from the 5'-non-coding region of human enteroviruses identified a local strain of coxsackie virus A21 in the muscle. Clinical symptomatology subsided with oral steroids.Conclusion: Local swelling mimicking a neoplasm may be related to infestation of coxsackie virus in muscle tissue. [ABSTRACT FROM AUTHOR]