Intrauterine Growth Retardation of Unknown Etiology. I. Serum Complement and Circulating Immune Complexes in Mothers and Infants

ABSTRACT: Complement (C) and circulating immune complexes (CIC) levels were measured in 22 full-term pregnant women and 15 of their small-for-gestational-age (SGA) offspring in order to seek evidence supporting an immunological etiology for placental lesions related to idiopathic intrauterine growth retardation. We used 19 normal full-term pregnant women and 18 of their infants with birthweight above the 25th centile of the ponderal curve as a control population for this study. C levels were significantly lower in mothers of SGA infants than in controls (146.6 ± 46.6 and 183.6 ± 36.6 respectively, p < 0.01). CIC were present in the sera of 5 out of 22 mothers of the SGA group and in 3 out of the 15 infants sera. No CIC were found in the sera of mothers or infants from the control group. Placental lesions were observed in 14 out of the 22 (64%) cases studied in the SGA group and in 1 of 11 (9%) of the controls. Two placentas from SGA infants showed acute atherosis, and deposits of IgM and C₃ were found in their vessel walls. These data are in favor of an immunological mechanism for intrauterine growth retardation of unknown etiology.     

RNA interference against enterovirus 71 infection

Enterovirus 71 (EV71) is a highly infectious major causative agent of hand, foot, and mouth disease (HFMD) which could lead to severe neurological complications. There is currently no effective therapy against EV71. In this study, RNA interference (RNAi) is employed as a therapeutic approach for specific viral inhibition. Various regions of the EV71 genome were targeted for inhibition by chemically synthesized siRNAs. Transfection of rhabdomyosarcoma (RD) cells with siRNA targeting the 3'UTR, 2C, 3C, or 3D region significantly alleviated cytopathic effects of EV71. The inhibitory effect was dosage-dependent with a corresponding decrease in viral RNA, viral proteins, and plaque formations by EV71. Viral inhibition of siRNA transfected RD cells was still evident after 48 h. In addition, no significant adverse off-target silencing effects were observed. These results demonstrated the potential and feasibility for the use of siRNA as an antiviral therapy for EV71 infections.     

Chronic serum sickness glomerulonephritis: Passive immunisation inhibits the removal of glomerular antigen and electron dense deposits

Summary Chronic serum sickness glomerulonephritis was induced in 20 Wistar rats, using radio-labelled, chemically cationised bovine serum albumin (BSA) as antigen. Four days after the last injection of antigen, when relocation of antigen within the rat had effectively ceased, the rats were given a single large intraperitoneal dose of either non-immune rat gamma globulin or anti-BSA rat gamma globulin. Ten days later the rats were killed. The rats which had received the anti-BSA globulin had significantly more antigen in renal cortex and in isolated glomeruli than the control group. They also had larger mesangial deposits as assessed by morphometry at electron microscope level; assessment of subepithelial deposits provided equivocal results. These findings provide direct confirmation that circulating antibody which is directed against an antigen which is trapped within deposits in the glomerulus will inhibit the removal of the antigen and deposits from the mesangium.     

Inhibition of heparin/protamine complex-induced complement activation by Compstatin in baboons

Complement activation products are major components of the inflammatory response induced by cardiac surgery and cardiopulmonary bypass which contribute to postoperative organ dysfunction, fluid accumulation, and morbidity. Activation of the complement system occurs during extracorporeal circulation, during reperfusion of ischemic tissue, and after the formation of heparin-protamine complexes. In this study we examine the efficacy of Compstatin, a recently discovered peptide inhibitor of complement, in preventing heparin/protamine-induced complement activation in baboons. The study was performed in baboons because Compstatin binds to baboon C3 and is resistant to proteolytic cleavage in baboon blood (similar to humans); Compstatin inhibits only the activation of primates' complement system. After testing various doses and administration regimens, Compstatin produced complete inhibition at a total dose of 21 mg/kg when given as a combination of bolus injection and infusion. Compstatin completely inhibited in vivo heparin/protamine-induced complement activation without adverse effects on heart rate or systemic arterial, central venous, and pulmonary arterial pressures. This study indicates that Compstatin is a safe and effective complement inhibitor that has the potential to prevent complement activation during and after clinical cardiac surgery. Furthermore, Compstatin can serve as the prototype for designing an orally administrated drug.     

Ability of rosetting or non-rosetting individual control and inflammatory macrophages to kill Escherichia coli X43 intracellularly

An autoradiographic method combined with a rosette technique was used to assess the bactericidal activity of individual control and inflammatory peritoneal macrophages (PM phi) in the presence or absence of expression of Fc receptor for IgG (FcR). There was a lack of FcR reactivity in a certain percentage of both categories of PM phi exposed to E. coli X43, a bacterium which is readily phagocytosed in the presence of specific antibody. Both rosetting and non-rosetting PM phi were capable of phagocytosing E. coli X43, but inflammatory PM phi showed a marked reduction in their capacity to ingest these bacteria compared with control PM phi. Once ingested the E. coli X43 were killed equally well by non-rosetting and rosetting control and inflammatory PM phi.     

Fc epsilon receptors on human cell lines and peripheral blood lymphocytes detected by binding of IgE immune complexes

To identify Fc epsilon receptors on human cell lines and peripheral blood lymphocytes, we developed a new method which relies on the binding of constructed immune complexes to Fc epsilon receptor-positive cells. Cell suspensions from either cell lines or peripheral blood lymphocytes were incubated with complexes of human myeloma IgE and murine monoclonal anti-human IgE at various ratios prior to cytocentrifugation. The complexes bound to the cells were subsequently visualized by immunoperoxidase staining. The specificity of this assay to detect cell surface Fc epsilon receptors was shown by the ability of human myeloma IgE to block the binding of the IgE complexes, resulting in unstained cells, whereas IgM, IgG, and IgA were unable to block the binding of the complexes (stained cells). This method is reproducible, allows quantification of a single sample at different times, and provides a record of the results. It can also be adapted to identify any cell surface receptor for which the ligand is known.     

Ultrastructural identification of the splenic follicular dendritic cells in the chicken

Background: There is a need to identify the follicular dendritic cells (FDC) of the chicken spleen at the ultrastructural level during a secondary immune response. Methods: The cells were identified after intravenous priming BSA and boosting with biotinylated BSA conjugated to colloidal gold particles. Monoclonal antibodies raised specifically either to chicken IgG or IgM were used to characterize these immune complex-trapping cells. Results: The FDC had an irregular morphology which varied through time, supporting the existence of two types of FDC in the chicken spleen, one showing filiform cell processes, the other provided with beaded dendrites. When the filiform dendrites were observed, the FDC bound the antigen on their surfaces. These dendrites showed an intrincate convoluted configuration, forming tightly wrapped networks near the cell body. The networks had the same features as those described in mammals as antigen retaining reticulum (ARR). In chickens, the ARR, which represents sites of antigen localization on FDC, reached maximum development on day 5 after the second injection of BSA and had disappeared by day 8. At this time FDC had beaded dendrites. Conclusions: Antigen is retained on FDC in the chicken spleen for long periods of time. © 1995 Wiley-Liss, Inc.     

Surface immunoglobulins mediate efficient transport of antigen to lysosomal compartments resulting in enhanced specific antigen presentation by B cells

A BCL₁ immunoglobulin (Ig) transfectant, expressing wild-type surface (s)IgM with the TEPC-15 idiotype (T15-Id) and anti-phosphorylcholine (PC) specificity, was previously shown to present PC-conjugated hen egg-white lysozyme (PC-HEL) to a HEL-specific T cell hybridoma at a lower antigen (Ag) concentration than that required for native HEL. Two variant Ig transfectants, expressing T15-Id sIgM with substitutions either in the entire spacer, transmembrane (TM) domain and cytoplasmic tail (B186 variant) or in the NH₂-terminal third of TM domain only (TM2 variant), failed to display this sIgM-mediated, enhanced presentation of PC-HEL at low concentrations. However, prolonged treatment with anti-T15-Id monoclonal antibody (mAb) led to a reduction of surface expression of the T15-Id sIgM in the wild-type and TM2 variant, but not in the B186 variant sIgM transfectants. Treatment with anti-T15-Id mAb also resulted in an increased intracellular accumulation of T15-Id sIgM in the wild-type transfectant, but not in the B186 variant. Subcellular fractionation analysis revealed that the ligands bound to the T15-Id sIgM are not efficiently transported to the dense lysosomal compartments in both B186 and TM2 transfectants, as compared to the wild-type sIgM transfectant. A significant increase in tyrosine phosphorylation after cross-linking of the T15-Id sIgM was observed only in the wild-type sIgM transfectant. These results suggest that, while the NH₂-terminal third of the TM region is not involved in the process responsible for the ligand-induced reduction of surface expression of sIgM, it appears to be essential for subsequent transport of sIgM/ligand complexes to the lysosomal compartments, as well as efficient activation of tyrosine kinases. These results strongly suggest that sIg-mediated enhancement of specific antigen presentation reflects the ability of sIg to efficiently transport antigen to the lysosomal compartments, and possibly the activation of protein tyrosine kinases.     

BDBPH—Zn Mn Cd双核配合物的稳定常数及其形态研究

目的测定BDBPH-Zn、Mn、Cd双核配合物的稳定常数,分析不同pH条件下各物种的存在形式及变化规律.方法温度25.0±0.10℃、离子强度0.100mol/L、N2保护下用NaOH标准溶液滴定大环配体BDBPH-金属离子(12)酸性溶液,滴定pH范围2～12,高精度酸度计记录pH值,BEST程序计算稳定常数,SPE和SPEPLOT程序绘制样品分布曲线.结果BDBPH-金属配合物的稳定常数分别为17.72(LogKLZn2),11.58(LogKLMn2),14.28(LogKLCd2).结论配体BDBPH能够与金属离子(Zn、Mn、Cd)形成稳定的双核配合物.