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Widening the martensitic hysteresis ( T Dhys ) in NiTiNb shape memory alloys (SMAs) holds potential for broadening their working temperature range while enabling the room-temperature storage. In this study, the T Dhys is divided into two parts: the thermal-induced hysteresis ( T hys ) and the deformation-induced hysteresis ( T hys ′ ). In addition to decreasing the martensitic transformation start temperature ( M S ), it is found that grain refinement is an effective method for widening both T hys and T hys ′ of the Ni47Ti44Nb9 alloy, a commercial SMA widely used for shape memory couplings. According to thermodynamic analysis, grain refinement increases the dissipation energy ( Δ E dis ) (caused by thermal friction at martensite/austenite interface), thereby widening T hys . Moreover, the Ni47Ti44Nb9 alloy with finer grains has the potential to release more elastic strain energy ( Δ E el ) after deformation, thereby exhibiting a wider T hys ′ . When deforming a large strain, the alloy with finer grains generates more dislocations which stabilize the martensitic phase, thus further widening T hys ′ . [ABSTRACT FROM AUTHOR]

The maximum recovery stress is an essential parameter for evaluating the reliability of shape-memory alloys. In this study, the factors that determine the maximum recovery stress of the Ni47Ti44Nb9 shape-memory alloy were investigated. Although the recovery stress is generated by the shape recovery during constrained heating, the maximum recovery stress mainly depends on plastic deformation rather than the shape recovery strain. In the present work, because of the softening effect caused by dislocation annihilation and grain coarsening, plastic deformation occurs more easily with the increase in annealing temperature. This results in a sharp decrease in the maximum recovery stress, while the recovery strain remains high. [ABSTRACT FROM AUTHOR]

The phase transformation and recovery stress of pre-deformed Ni47Ti44Nb9 alloy are systematically investigated during constrained heating, cooling and thermal cycling. Recovery stress is determined by a phase transformation, thermal expansion, and contraction. Reverse martensitic transformation occurs during constrained heating and then results in a sharp increase in the recovery stress. Meanwhile, the wide phase transformation hysteresis shrinks during thermal cycling. A few martensitic transformations gradually occur across a wide temperature range during constrained cooling, resulting in a negative decreasing stage or a wide plateau of recovery stress. When cooled further to a critical value of 20 °C, the recovery stress and temperature follow the Clausius–Clapeyron equation, and large amounts of martensitic transformations appear, resulting in the sharp decrease of the recovery stress. [ABSTRACT FROM AUTHOR]

Despite the extensive use of Sn-Ag-Cu as a Pb-free solder alloy, its melting point is significantly higher than that of eutectic Sn-Pb solder. Sn-Ag-Bi-In solder is an alternative Pb-free solder, with a melting temperature close to that of eutectic Sn-Pb. This study elucidates the electromigration behavior of Sn-Ag-Bi-In solder and then compares the results with those of the Sn-Ag-Bi system. The behavior of Pb-free Sn-Ag-Bi-In solder strips under electromigration is examined by preparing them in Si (001) U-grooves. The samples are then tested under various temperatures and current densities. Although the compounds thicken near both electrodes with current stressing, the thickness at the anode exceeds that at the cathode. Experimental results of the average failure time indicate that Sn-Ag-Bi-In solder has a longer lifetime than does Sn-Ag-Bi, which is attributed to the ζ phase. Additionally, the ζ phase dissolved by the current in the early stage replenishes the outgoing atomic flux. These atomic fluxes also enhance the growth of abnormally large particles in the middle of the strips. Field-emission electron probe microanalysis (FE-EPMA) results indicate that the amount of indium is reduced after the ζ phase near the cathode is exhausted for extended current stressing time. [ABSTRACT FROM AUTHOR]

Third-order explicit autonomous differential equations in one scalar variable, sometimes called jerky dynamics, constitute an interesting subclass of dynamical systems that can exhibit chaotic behavior. In this paper, we investigated a simple jerk system with a piecewise exponential nonlinearity by numerical examination as well as dynamic simulation. Using the largest Lyapunov exponent as the signature of chaos, the region of parameter space exhibiting chaos is identified. The results show that this system has a perioddoubling route to chaos and a narrow chaotic region in parameter space. The rescaled system is approximately described by a one-dimensional quadratic map. The parameters are fitted to a simple function to predict the values for which chaos occurs in the case of high nonlinearity where the region in parameter space that admits chaos is relatively small. [ABSTRACT FROM AUTHOR]

Objectives: Initiation and maintenance of pro-inflammatory reactions elicited by bacterial lipopolysaccharide and/or cytokines in the macrophage lineage have been reported to play a crucial role in acute and chronic pathogenic effects. Whether pro-inflammatory responses triggered by lipopolysaccharide in growth arrested cells differ from those in proliferating cells remains unanswered. Materials and methods: Olomoucine and roscovitine are cyclin-dependent kinase (CDK) inhibitors that prevent progression through the cell cycle. After treatment with CDK inhibitors, expression of pro-inflammatory genes was analysed by reverse transcriptase–polymerase chain reaction. Protein levels of inducible nitric oxide synthase (iNOS) and nuclear factor kappaB (NF-κB) were determined by Western blotting. Promoter activity of iNOS was measured by the luciferase activity assay. Results: In this study we have demonstrated that both olomoucine and roscovitine inhibit cell proliferation and diminish nitric oxide production and cytokine gene expression, in lipopolysaccharide-stimulated murine RAW264.7 macrophages. In addition, olomoucine reduces iNOS promoter activity and alleviates NF-κB transcription activation. After co-transfection with E2F1 interference RNA, suppression of lipopolysaccharide-mediated iNOS promoter activity and NF-κB activation was observed. Furthermore, we demonstrated that olomoucine-induced growth arrested cells reduce expression of the p65 subunit of NF-κB. Conclusions: The findings of this study suggest that inhibition of cell-cycle progression is capable of reducing pro-inflammatory responses via down-regulation of NF-κB. [ABSTRACT FROM AUTHOR]

Amyloid precursor protein (APP) has several caspase cleavage sites in its C-terminal cytoplasmic domain and N-terminal extracellular domain. Caspase cleavages of APP at its cytosolic tail may result in releasing the domain and inducing cell death. During apoptosis, the N-terminal domain may also be processed at amino acids 197 and 219 by caspases leading to unmasking of an acidic-rich region (AR). In this study, AR-exposing APP was shown to inhibit cell growth after transfection into RBA-1 astrocytes and BV-2 microglial cells. The recombinant AR from residue 220 to 288 of APP (APP220–288) was produced and its biological activities were analyzed. APP220–288 induced morphological changes, cell death, and DNA fragmentation in BV-2 and RBA-1 cells. However, AR was determined to have no apparent effects in suspension cells, erythroleukemia K562 cells, and Jurkat T cells. The cytotoxicity was depending on negative charge cluster and the apoptotic activity of AR was attributed to the inhibition of cell adhesion. In BV-2 microglial cells, AR significantly stimulated Fas expression, although expressions of the pro-inflammatory cytokine genes were not detected. APP220–288 also induced nitric oxide synthase (iNOS) expression and nitric oxide (NO) production. These findings indicate that the acidic-rich domain of APP may have apoptotic activity due to inhibition of cell adhesion and induction of iNOS and Fas expressions. Moreover, unmasking the apoptosis-induced AR may activate and exacerbate glial cells which in turn lead to further progression of the death program. [ABSTRACT FROM AUTHOR]

Summary Decreased number and impaired functions of polymorphonuclear neutrophils (PMN) due to the presence of anti-PMN autoantibodies in the serum render patients with systemic lupus erythematosus (SLE) susceptible to bacterial infections. However, the cognate antigens and pathological mechanisms of anti-PMN autoantibodies in SLE are rarely reported in the literature. In this study, we found approximately 20% of SLE sera contained anti-PMN autoantibodies detected by human PMN-coated cellular ELISA. A membrane protein with molecular weight of 50 kDa was identified as the cognate antigen of anti-PMN in Western blot after membrane-biotinylation and streptavidin column elution. The 50 kDa molecule was proved to be SSB/La after immunoscreening, molecular cloning and nucleotide sequencing of the gene from the human leucocyte cDNA library. Human anti-SSB/La autoantibodies purified from active SLE sera passing through the recombinant SSB/La conjugated Sepharose 4B affinity column could bind and penetrate into normal human PMN. Functional analysis revealed that the anti-SSB/La autoantibodies exerted a number of potent effects on human PMN, including suppressed phagocytosis, accelerated apoptosis and enhanced IL-8 production. These in vitro results suggest that anti-SSB/La is one of the anti-PMN autoantibodies capable of penetrating into PMN and responsible for neutropenia and functional impairment of PMN in patients with SLE. [ABSTRACT FROM AUTHOR]

SUMMARY To determine the biological functions of membrane expressed CD45 isoforms on polymorphonuclear neutrophils (PMN), the monoclonal IgG F(ab′)2 antibody against CD45, CD45RA or CD45RO was used as surrogate ligand for binding with these molecules on PMN. We found 99·5 ± 3·2%, 42·3 ± 5·8% and 96·7 ± 2·6% PMN expressed CD45, CD45RA and CD45RO molecules on the cell surface, respectively. The interaction of CD45, CD45RA or CD45RO with its specific antibody on PMN enhanced phagocytosis markedly (34–83% increase), mainly via increased expression of complement receptor type 3 (CR3, CD11b) on the cells. The production of IL-8 by PMN was also increased significantly after binding with antibodies (anti-CD45 > anti-CD45RO > anti-CD45RA). Anti-CD45RA and anti-CD45RO, but not anti-CD45, enhanced TNF-α mRNA expression and decreased protein tyrosine phosphorylation of PMN. However, only anti-CD45RO suppressed Src family protein tyrosine kinase p56lck expression in the cells. These results suggest that the cross-linking of CD45 isoforms by their specific antibodies stimulated different PMN activities by differential suppression on protein tyrosine phosphorylation and Src family tyrosine kinase p56lck . [ABSTRACT FROM AUTHOR]

Objective and Design: To determine whether anti-double stranded DNA antibody (anti-dsDNA) can affect the synthesis of eicosanoids and cytokines in rat glomerular mesangial cells (RMC).¶ Materials or Subjects: Glomerular mesangial cells were isolated and subcultured from Sprague-Dawley rats. Monoclonal anti-dsDNA (12B3 clone) was derived from autoimmune MRL-lpr/lpr mouse by hybridoma technology.¶ Methods: The mRNA expression of cyclo-oxygenase type 1 (COX-1), type 2 (COX-2), Th1 (IL-2 and IFN- γ)/Th2 (IL-4 and IL-10) and proinflammatory (IL-6 and TNF- α) and anti-inflammatory (TGF- β) cytokines of RMC ± anti-dsDNA was detected by RT-PCR. The PGE2 production by RMC ± anti-dsDNA was measured by ELISA. The statistical significance was assessed by non-parametric Wilcoxon signed rank test.¶ Results: We found RMC spontaneously expressed COX-1, but not COX-2. The incubation of RMC with anti-dsDNA (50ng/ml) did not affect COX expression and PGE2 production by RMC. RMC also spontaneously expressed IL-6, TNF- α and TGF- β mRNA. However, only IL-6 was up-regulated by anti-dsDNA.¶ Conclusions: Increased IL-6 expression in RMC may become a marker of anti-dsDNA-mediated immune damage of mesangial cells.¶ [ABSTRACT FROM AUTHOR]

Summary In our previous reports, we found polyclonal anti‐double‐stranded DNA antibodies (anti‐dsDNA) purified from patients with active systemic lupus erythematosus (SLE) exerted inhibitory effect on [3H]thymidine incorporation of human mononuclear cells (MNC). However, the other immunological effects of anti‐dsDNA on the functions of MNC have not yet been reported. In this study, two monoclonal antibodies, 12B3 and 9D7, with different anti‐dsDNA activity were evaluated for their effects on the expression and release of different cytokines from human MNC. We confirmed absence of endotoxin in the two monoclonal antibody preparations and the used medium as detected by Limulus amoebocyte lysate test. The mRNA expression and release of different cytokines including interleukin (IL)‐1β, IL‐2, IL‐4, IL‐6, IL‐8, IL‐10, tumour necrosis factor‐α (TNF‐α) and interferon‐γ (IFN‐γ) were measured. We found the two monoclonal anti‐dsDNA not only dose‐responsively suppressed the phytohaemagglutinin (PHA)‐induced thymidine uptake of human MNC but stimulated the mRNA expression of IL‐1β, IL‐6 and IL‐8 in normal human MNC detected by reverse transcription–polymerase chain reaction (RT–PCR). Enzyme‐linked immunosorbent assay (ELISA) measurement of cytokines in MNC culture supernatants revealed that anti‐dsDNA enhanced IL‐1β, IL‐8, TNF‐α and IL‐10 release from resting MNC. These effects of anti‐dsDNA antibodies were not affected by polymyxin B, a potent binder and neutralizer of lipopolysaccharide (LPS). These in vitro studies suggest that anti‐dsDNA possess a dual effect on normal human MNC: (a) to enhance the release of proinflammatory cytokines (IL‐1β, IL‐8 and TNF‐α) from MNC to... [ABSTRACT FROM AUTHOR]

Objective: To investigate whether interleukin-13 (IL-13) can affect arachidonic acid metabolism and phagocytic activity of normal human polymorphonuclear neutrophils (PMN).¶ Methods: Normal human PMN (1 × 106 cells/ml) were incubated with different concentrations of IL-13 (0.1–10 ng/ml) for a variety of times (30–120 min). Phagocytosis and intracellular cyclooxygenase-2 (COX-2) were detected by flow cytometry. The expression of COX-1 and COX-2 mRNA was detected by RT-PCR. The concentration of PGE2 in the PMN cultured supernatants was determined by EIA.¶ Results: We found that IL-13 at an optimal concentration of 1 ng/ml significantly enhanced COX-2 gene expression and PGE2 production (121.57 ± 22.17 pg/ml in IL-13 stimulation vs. 73.16 ± 11.72 pg/ml in controls) by PMN. In addition, IL-13 stimulated PMN phagocytosis via increased complement receptor type 1 (CR1) and type 3 (CR3), but not IgG Fcγ receptor type 3 (FcγRIII). The cytoplasmic neutral esterase activity of PMN was also enhanced by IL-13 stimulation for 24 h.¶ Conclusions: These results suggest that IL-13 can stimulate PMN and modulates the inflammatory reactions via the cyclooxygenase pathway. [ABSTRACT FROM AUTHOR]

Affinity-purified polyclonal anti-double-stranded DNA (anti-dsDNA) antibodies from patients with systemic lupus erythematosus (SLE) exert a cytostatic effect on cultured rat glomerular mesangial cells (MC). The cognate antigens expressed on the surface of MC have been proved to be acidic ribosomal phosphoproteins (P proteins) in our previous study. The mesangial cytostatic effect of anti-dsDNA antibodies is attributed to the cross-reactivity of the antibodies with membrane-expressed P proteins, but not to the effect of minute amounts of anti-ribosomal P proteins antibodies contained in the anti-dsDNA preparations. Immunofluorescence staining of the native cells demonstrated that anti-dsDNA antibodies bound to the surface of rat mesangial cells, rat brain astrocytes (RBA-1) and mouse fibroblasts (3T3). Anti-dsDNA antibodies also exert potent cytostatic effects on these cells in a dose-dependent manner. [ABSTRACT FROM AUTHOR]

Affinity-purified human polyclonal anti-double-stranded DNA antibodies (anti-dsDNA) exerted a cytostatic effect towards human and rat glomerular mesangial cells (MC). In order to identify the cognate antigens for anti-dsDNA on the surface of MC, we used these autoantibodies to probe a human renal λg11 cDNA expression library. Two cDNA clones encoding the cognate proteins for the autoantibodies were isolated. Sequencing analysis of the two cDNA showed that they had 98.6% homology with the gene of the P0 and 99.2% homology with the gene of the Pi human acidic ribosomal phosphoproteins (P protein). Two galactosidase fusion proteins (125 000 and 150 000 MW) derived from the two cDNA inserts expressed in lysogenic Escherichia coli Y1089 could react with the original screening antibodies in an immunoblotting analysis. After transformation and expression of the full-length P1 clone in prokaryotic cells, the purified P1 protein was able to react with anti-dsDNA. In a cross-inhibition experiment, the dsDNA binding activity of anti-dsDNA was inhibited by a synthetic polypeptide corresponding to the carboxyl terminal 20 amino acids of P protein and purified P1 protein in a dose-dependent manner, but this was less potent than the inhibition caused by calf thymus dsDNA. By use of well-defined systemic lupus erythematosus (SLE) sera, we found only sera containing a high titre of anti-dsDNA activity (>300 IU/ml) reacted with P1 of rat MC lysate. Furthermore, the 38000 and 19000 MW macromolecules were proved to be the cognate antigens for anti-dsDNA expression on the surface of the MC, by Western blot of the MC plasma membrane lysates. These results suggest that antidsDNA may cross-react with ribosomal P proteins expressed on the surface of the MC and exert cytostasis towards these cells. [ABSTRACT FROM AUTHOR]

Interleukin-1 receptor antagonist (IL-lra) binds competitively to IL-1 receptors but does not transduce the signal which blocks the biological activities induced by IL-1. In this study, polymorphonuclear neutrophils (PMN) and mononuclear cells (MNC from the patients with active systemic lupus erythematosus (SLE) ( = 11), inactive SLE ( = 13) and normal individuals ( = 13) were compared for the IL-lra producing capacity of these cells. PMN and MNC at a concentration of 1 × 10 cells/ml were incubated with medium alone (spontaneous) or stimulated with lipopolysaccharide (LPS, 100 ng/ml) for 24 h. The IL-lra concentration in the supernatants was quantified by ELISA method. Both spontaneous and LPS-stimulated production of IL-lra by PMN, but not by MNC, of active SLE were significantly lower than that of inactive SLE or normal groups. Prednisolone (1 and 5 μg/ml) did not change the production of IL-lra by normal PMN either spontaneously or LPS-stimulation in study. Moreover, the IL-lra producing capacity of PMN in seven active SLE on admission and after intensive immunosupprcssive treatment was measured. These results suggest that the defective IL-lra production by SLE-PMN is relevant to disease activity and may be regarded as a new indicator of disease activity in patients with active SLE. [ABSTRACT FROM PUBLISHER]

Cytidine deaminase activity (CD) in the neutrophil culture supernatants (PMN SUP) of 27 patients with systemic lupus erythematosus (SLE) was measured using a spectrophotometric method. Compared with the controls (5.449±1.358 U/5 × 10 PMN), the CD activity in the spontaneous culture supernatants of PMN was significantly increased in active (10.003±2.637 U/5 × 10 PMN) but not in inactive (5.358±1.624 U/5 × 10 PMN) SLE. However, after stimulation with -formyl-methionyl-leucyl-phenylalanine (FMLP, 1 × 10 M), the ratio of enzyme activity between stimulated and spontaneous PMN supernatants was decreased in active SLE (0.794±0.178) compared with normal controls (1.300±0.225). In contrast, the enzyme activity in the cytoplasm of either stimulated or non-stimulated PMN was not different among these three groups. These results suggest that CD of PMN is releasable and can be enhanced by chemotactic factor stimulation in normal PMN. The increased spontaneous release of CD by active SLE PMN is one of the indicators for the disease activity in these patients. [ABSTRACT FROM PUBLISHER]

The MRL-lpr/lpr and MRL-++ mice were studied for the expression of cytokines in the spleen, lymph node, thymus, kidney and brain through the reverse transcription-polymerase chain reaction (RT-PCR). The frequencies of IL-4 and TNF-α expression in the thymus and spleen were significantly higher in MRL-lpr/lpr mice than in MRL-++ mice from the age of 17 to 32 weeks. More importantly, IL-4 transcript was demonstrated in the early rather than in the terminal stage of the lupus disease. At the 20th week, MRL-lpr/lpr mice with active disease exhibited higher concentrations of IL-1α, IL-6 and TNF-α in serum than MRL-++ mice. Interestingly, in MRL-lpr/lpr but not MRL-++ mice, the IL-6 concentration in culture supernatants of the thymic cells was significantly higher than that of the splenic or lymph node cells. On the other hand, IL-6 and IL-1β were expressed in the brain and kidney of MRL-lpr/lpr mice but not of MRL-++ mice. Cultured MRL-lpr/lpr mesangial cells could also express IL-6 but to a lesser extent. These results suggest that the abnormal splenic and thymic IL-4 and TNF-α expression may predispose the development of autoimmune reactions. The expression of IL-1β and IL-6 in the brain and kidney may be implicated in the damage of these two organs in MRL-lpr/lpr mice. [ABSTRACT FROM AUTHOR]

Polyclonal anticardiolipin antibodies purified from pooled serum samples of patients with systemic lupus erythematosus were shown to have inhibitory effects on cultured normal rat brain astrocytes (RBA-1 cells). Anticardiolipin antibodies at concentrations from 50 to 200 micrograms/ml inhibited the [3H]thymidine incorporation of RBA-1 cells in a dose dependent manner after three days of culture. A kinetic study showed that anticardiolipin antibodies (100 micrograms/ml) maximally inhibit the proliferation of RBA-1 cells (20.6 (5.1)% of the control value) after incubation for one day. In contrast, human gamma globulin (100 micrograms/ml) had no effect on these cells. In the presence of anticardiolipin antibodies (100 micrograms/ml), the RBA-1 cells attached to the bottom of wells became spherical and the expression of glial fibrillary acidic protein in the cytoplasm was slightly reduced. Using 3,3'-dihexyloxacarbocyanine iodide as an indicator, anticardiolipin antibodies depolarised the membrane potential of RBA-1 cells after one day of culture. In addition, the percentage binding of RBA-1 cells with anticardiolipin antibodies was greater than with gamma globulin as determined by flow cytometric analysis. Immunofluorescence staining of brain tissue from BALB/c mice with anticardiolipin antibodies was noted in the corpus callosum, the cellular zone near the corpus callosum, and cells scattered in brain tissue. These results suggest that anticardiolipin antibodies have an inhibitory effect on brain cells and elicit thrombus formation in brain vessels, which plays a part in neuropsychiatric lupus. [ABSTRACT FROM PUBLISHER]

Samples of protein from the urine of 23 patients with lupus nephropathy and 15 patients with proteinuria who did not have systemic lupus erythematosus (SLE) were studied for the presence of cytokines, soluble interleukin 2 receptors (sIL-2R), and free light chain immunoglobulins. The patients with lupus nephropathy were divided into two groups with active (nephritis) and inactive inflammation (nephrosis) based on the results of the analysis of urine samples and renal histology. The crude urine proteins (5 mg/ml) after precipitation by 80% ammonium sulphate from 14 patients with lupus nephritis contained higher concentrations of sIL-2R (4.88 (SEM 1.27 ng/ml) than those from nine patients with nephrosis (1.11 (0.52) ng/ml) or 15 patients without SLE (1.31 (0.87) ng/ml). The concentration of sIL-2R in protein from urine samples was not correlated with the concentration in plasma and was inversely correlated with the excretion of protein in urine over 24 hours in patients with SLE. It is suggested that, in addition to leakage from the circulation, the local production of sIL-2R by inflamed kidneys is possible. The crude proteins in urine were further fractionated by gel filtration on Sephacryl S-200. Arbitrarily, four fractions could be obtained from urine from patients with SLE but only three fractions were found in the urine of patients without SLE. Fraction IV derived from patients with nephritis or nephrosis augmented the pokeweed mitogen induced [3H]thymidine uptake of mononuclear cells. In addition, the positive rates of free kappa (kappa) (35.7%) and lambda (lambda) (42.9%) chains in proteins in urine from nephritic patients were higher than those in the other two groups. These results suggest that the severity of inflammation in the kidneys of patients with lupus can be reflected by the increased excretion of sIL-2R, free light chain immunoglobulins, and cytokine-like molecules in urine. [ABSTRACT FROM PUBLISHER]

Polyclonal antibodies to double stranded DNA (dsDNA) purified from pooled serum samples of patients with systemic lupus erythematosus (SLE) exerted cytotoxic effects on cultured rat mesangial cells. At concentrations from 5 to 150 IU/ml, antibodies to dsDNA inhibited the incorporation of thymidine labelled with 3H into rat mesangial cells in a dose response manner after three days of culture. In contrast, normal human IgG (1 mg/ml), heat aggregated human IgG (1 mg/ml), N-formyl-methionyl-leucyl-phenylalanine (1 x 10(-7) mol/l), tumour necrosis factor alpha (16 U/ml), lipopolysaccharides (1 microgram/ml), 4 beta-phorbol-12 beta-myristate-13 alpha-acetate (PMA) (20 ng/ml), interleukin 1 beta (10 U/ml), and 20% v/v phytohaemagglutinin stimulated mononuclear cell supernatant showed no significant effect on these cells. Anticardiolipin antibody, another autoantibody purified from the serum of patients with SLE, also inhibited the proliferation of rat mesangial cells but to a lesser extent. In the presence of antibodies to dsDNA (100 IU/ml), the mesangial cells became spherical and clustered together, which was very different from the original stellate appearance. These autoantibodies also depolarised the membrane potential of mesangial cells. Antibodies to dsDNA decreased the syntheses of prostaglandin E2, 6-keto-prostaglandin F1 alpha and thromboxane B2 by mesangial cells. In an in vivo study, the antibodies to dsDNA showed a strong affinity for the glomeruli when intravenously injected into rats. These results suggest that the nephrotropic antibodies to dsDNA can directly damage the glomerular mesangial cells in addition to the formation of immune complexes with DNA which may cause kidney inflammation and tissue destruction. [ABSTRACT FROM PUBLISHER]

Anticardiolipin antibodies purified from serum from patients with systemic lupus erythematosus (SLE) by cardiolipin micelles were studied for their effects on lymphocytes and neutrophils. At a concentration of 160 micrograms/ml they markedly suppressed the [3H]thymidine incorporation of mononuclear cells stimulated by phytohaemagglutinin (4.9 (SEM 1.9%) of the control) and pokeweed mitogen (26.7 (10.5%) of the control). In addition, anticardiolipin antibodies changed the cell cycle of phytohaemagglutinin stimulated lymphocytes such that the S and G2+M phases were significantly diminished (G0/G1 = 64.62%, S = 20.59%, G2+M = 14.78% in the presence of normal human IgG v G0/G1 = 86.07%, S = 10.32%, G2+M = 3.59% in the presence of anticardiolipin antibodies). The suppression of lymphocyte proliferation by anticardiolipin antibodies was shown not to be caused by an alteration of T cell subpopulations. However, the interleukin 2 receptors on the cell surface and the soluble interleukin 2 receptors in the supernatant of phytohaemagglutinin stimulated mononuclear cells were decreased in the presence of anticardiolipin antibodies. On the other hand, the phagocytic activity of neutrophils was 40% inhibited at a higher concentration of anticardiolipin antibodies (300 micrograms/ml) through suppression of C3b/C4b and Fc receptors on polymorphonuclear leucocytes. These results suggest that anticardiolipin antibodies exert inhibitory effects on both lymphocytes and phagocytes in addition to the coagulation cascade. These newly found activities of anticardiolipin antibodies were mediated by the non-specific membranotropic property of the antibodies. [ABSTRACT FROM PUBLISHER]