急性梗阻性化脓性胆管炎的临床诊治研究

目的探讨急性梗阻性化脓性胆管炎的诊断和治疗,提高治愈率,减少死亡率。方法对65例本院收治的急性梗阻性化脓性胆管炎病例进行回顾性分析。结果 62例行手术治疗,3例行内镜括约肌乳头切开取石术,结果55例治愈,7例好转,死亡3例。结论明确诊断后及早手术,合理选择术式,是提高治愈率、降低死亡率的关键。     

抗晶状体蛋白的特异性抗体免疫示踪研究

目的：了解针对晶状体组织的特异性抗体到达眼前节的途经、部位及其对晶状体生理功能的影响。方法：采用荧光标记抗体，观察被动免疫动物眼前节组织中荧光反应的变化，测定晶状体调节力和进行眼前节裂隙灯检查。结果：特异性抗体(IgG)首先到达睫状体部，而后出现在晶状体囊膜、虹膜和角膜内皮上；眼前节抗体含量峰值与裂隙灯观察的房闪、即同时出现；晶状体上皮细胞的损伤与晶状体的调节力下降则出现于转移免疫后2w。结论：针对晶状体组织抗原的特异性抗体可通过体循环先到达睫状体部，然后随房水而作用于晶状体上皮细胞。     

Analysis of gene expression in MOG-induced experimental autoimmune encephalomyelitis after treatment with a novel brain-penetrating antioxidant

Accumulating data from experimental studies indicate that oxidative stress has a major role in the pathogenesis of multiple sclerosis (MS). It has been suggested that local production of reactive oxygen species, probably by macrophages, mediates axonal damage in both MS patients and the mouse model experimental autoimmune encephalomyelitis (EAE). We have shown previously that our novel brain-penetrating antioxidant, N-acetylcysteine amide (AD4), reduces the clinical and pathological symptoms, including inflammation and axonal damage in myelin oligodendrocyte glycoprotein (MOG)-induced chronic EAE in mice. The aim of this study was to examine the molecular mechanism by which AD4 exerts protection in MOG-induced EAE mice. Therefore, we analyzed gene-expression profile in the spinal cords of MOG-induced chronic EAE mice and compared them with MOG-induced mice treated with AD4, using a cDNA microarray. We found that MOG treatment up-regulated genes encoding growth factors, cytokines, death receptors, proteases, and myelin structure proteins, whereas MOG- and AD4-treated mice demonstrated gene expression profiles similar to that seen in na?ve healthy mice. In conclusion, our study shows that chronic AD4 administration suppresses the induction of various pathological pathways that play a role in EAE and probably in MS.     

Elevated anti-alginate serum titers in patients with acute cholangitis and gallstones imbedded withPseudomonas aeruginosa

Electron microscopy and bacteriological culture revealed viable bacteria covered with a glycocalyx (biofilm) in choledochal stones recovered from two patients with acute cholangitis. On the cut surface of the choledochal stones, the cholesterol stone component was surrounded with a layer of brown pigment stone. In each case, bacterial culture of the choledochal stone recoveredPseudomonas aeruginosa. Since alginate is the main component of the glycocalyx produced byP. aeruginosa, serum IgM, IgG and IgA anti-alginate antibodies were measured in each patient. The present study is the first to demonstrate acute and transient IgM seroconversion to alginate in cases of acute cholangitis. In one case, the elevation of anti-alginate IgM preceded the elevation of anti-alginate IgG. The authors propose that the bacterial glycocalyx may play a significant role in acute cholangitis.     

Antibody Mediated Complete Congenital Heart Block in the Fetus

Complete congenital heart block (CCHB) affects 1:20,000–25,000 live births and is usually an atrioventricular block; 30–50% of fetuses with CCHB will have a structural anomaly, though recently attention has focused on the etiological influence of autoimmune disease, such as systemic lupus erythematosus. The diagnosis is established by detailed two-dimensional ultrasound scanning of the heart to exclude anomaly coupled with M-mode echocardiography and Doppler blood velocity patterns in the major vessels to detect the uncoupling of atrial and ventricular rhythms. Risk factors for an affected child are discussed. A previously affected child, high titers of anti-Ro antibodies, the presence of anti-Ro (SS-A) and anti-La (SS-B), and maternal HLA DR3 confer high risk. Antibody mediated CCHB is irreversible. Plasmapheresis and immunosuppression have been attempted in affected mothers, with limited success, to reduce the likelihood of the fetus being affected, and steroids have been used to reduce the inflammatory reaction in the heart. In many cases the underlying pathology of the immune system adversely affects utero-placental function requiring careful monitoring of fetal well-being. CCHB renders fetal heart rate monitoring virtually useless, in the antenatal and intrapartum periods. Alternatives are explored.     

Granulocyte-macrophage colony stimulating factor inhibits class II major histocompatibility complex expression and antigen presentation by microglia

Granulocyte-macrophage colony stimulating factor (GM-CSF) modulates various functions of monocytes/ macrophages including antigen-presenting capacity. Recently it was found that astrocytes produce GM-CSF in the central nervous system (CNS) and that GM-CSF can induce proliferation and morphological changes of microglia. Here we show that GM-CSF can down regulate the interferon-γ-mediated induction of major histocompatibility complex (MHC) class II antigens in microglia, but not in astrocytes. GM-CSF pretreatment completely prevents myelin basic protein-specific T cell proliferation induced by microglia but not astrocytes. GM-CSF did not affect the cell surface expression on microglia of either MHC class I or cell adhesion molecules. The inhibition of microglial MHC class II expression and antigen-presenting function is specific for GM-CSF, as treatment with a different CSF (interleukin-3) did not modulate microglial phenotype or functional capacity. These data suggest that GM-CSF might be involved in the regulation of immune responses within the central nervous system.     

Bound immunoglobulins of classes M,A, and G studied in the thymus of patients with myasthenia gravis

Deposits of granular material containing immunoglobulins (Ig) of the M, A, and G classes, were found by direct immunofluorescence in the thymus of patients with myasthenia. Treatment of sections of the thymus of myasthenic patients with unlabeled preparations against individual classes of human Ig inhibits the reaction of the granular material with homologous labeled preparations. Disappearance of fluorescence of the deposits also was observed in sections treated with glycine-HCl buffer, pH 2.8. These results suggest that the granular material consists of immune complexes in which IgM, IgA, and IgG act as antibodies and components of the thymus tissues as the antigen. The presence of bound Ig in the thymus is evidence that in myasthenia an autoimmune process directed against the tissues of this organ is involved.Laboratory of Streptococcal Infections, N. F. Gamaleya Institute of Epidemiology and Microbiology. Professorial Surgical Department, I. M. Sechenov First Moscow Medical Institute. Laboratory of Clinical Pathophysiology, Institute of General and Pathological Physiology, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR M. I. Kuzin.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 85, No. 6, pp. 709–712, June, 1978.     

Fine specificity of autoantibodies to calreticulin: epitope mapping and characterization

Extracellular calreticulin (CRT) as well as anti‐CRT antibodies have been reported in patients with various autoimmune disorders and CRT has been implicated in ‘epitope spreading’ to other autoantigens such as the Ro/SS‐A complex. In addition, antibodies against parasite forms of the endoplasmic reticulum chaperone, CRT, have been found in patients suffering from onchocerciasis and schistosomiasis. In this study, we screened sera for anti‐CRT antibodies from patients with active and inactive systemic lupus ertythematosus (SLE) and primary or secondary Sjögren’s syndrome. Approximately 40% of all SLE patients were positive for anti‐CRT antibodies. The antigenic regions of CRT were determined using full length CRT and fragments of CRT prepared in yeast and Escherichia coli, respectively. Synthetic 15mer peptides corresponding to the major autoantigenic region of CRT (amino acids 1–289), each one overlapping by 12 amino acids, were used to map the B cell epitopes on the CRT protein recognized by autoimmune sera. Major antigenic epitopes were found to be associated with the N‐terminal half of the protein in 69% of the SLE sera from active disease patients, while the C‐domain was not antigenic. Major epitopes were found to be reactive with antibodies in sera from SLE patients with both active and inactive disease, spanning different regions of the N and P‐domains. Sera from both healthy and disease controls and primary Sjögren’s syndrome patients were non‐reactive to these sequences. Limited proteolysis of CRT with two major leucocyte serine proteases, elastase and cathepsin G, demonstrated that an N‐terminal region of CRT is resistant to digestion. Interestingly, some of the epitopes with the highest reactivity belong to the fragments of the protein which bind to C1q and inhibit complement activation. Whether C1q association with CRT is a pathological or protective interaction between these two proteins is currently under investigation.     

Unaltered thyroid function in mice responding to a highly immunogenic thyrotropin receptor: implications for the establishment of a mouse model for Graves' disease.

Grave's disease (GD) is a common disorder characterized by the presence of autoantibodies to the thyrotropin receptor. In the past, the exceedingly low expression of the thyrotropin receptor on thyrocytes has not allowed its purification in quantities sufficient to investigate the establishment of an animal model for this disease. In this study, we have purified the 398-amino acid, extracellular region of the human thyrotropin receptor (TSH-R.E) from insect cells using recombinant baculovirus, and explored its immunopathogenic properties in H-2b,d,q,k,s strains of mice. The receptor preparation was highly immunogenic since it elicited strong specific proliferative T cell responses as well as IgG responses in all strains tested. In addition, hyperimmunization with TSH-R.E induced (i) serum antibodies that blocked the binding of 125I-TSH to its receptor, a common feature of GD autoantibodies; and (ii) IgG that reacted with a synthetic peptide (residues 32-54) from the N-terminus of the receptor, a region implicated in the binding of thyroid stimulating antibodies. In SJL animals only, a weak antibody response to two other thyroid antigens, thyroglobulin and thyroid peroxidase, was also observed. The presence of these antibodies, however, was not accompanied by a detectable alteration in thyroid function as assessed by the measurement of serum TSH, T4 and iodine levels. Also mononuclear infiltration of the thyroid gland or morphological changes compatible with an activation state of thyrocytes were not apparent in TSH-R-challenged mice. In contrast, mice treated with the anti-oxidant aminotriazole showed a dramatic increase in serum TSH levels and an activated follicular epithelium. These data demonstrate that a highly immunogenic TSH-R.E in mice does not necessarily provide a proper stimulus for the induction of a hyper- or hypothyroid status as defined by hormonal or histological criteria. Main reasons for the inability to induce receptor-specific antibodies that affect thyroid function such as those generated in GD are likely to be the inappropriate folding of the recombinant extracellular domain of the receptor, or the xenogeneic nature of the autoantigen.     

Targeting lymphocyte activation through the lymphotoxin and LIGHT pathways

Summary: Cytokines mediate key communication pathways essential for regulation of immune responses. Full activation of antigen-responding lymphocytes requires cooperating signals from the tumor necrosis factor (TNF)-related cytokines and their specific receptors. LIGHT, a lymphotoxin-β (LTβ)-related TNF family member, modulates T-cell activation through two receptors, the herpesvirus entry mediator (HVEM) and indirectly through the LT-β receptor. An unexpected finding revealed a non-canonical binding site on HVEM for the immunoglobulin superfamily member, B and T lymphocyte attenuator (BTLA), and an inhibitory signaling protein suppressing T-cell activation. Thus, HVEM can act as a molecular switch between proinflammatory and inhibitory signaling. The non-canonical HVEM–BTLA pathway also acts to counter LTβR signaling that promotes the proliferation of antigen-presenting dendritic cells (DCs) within lymphoid tissue microenvironments. These results indicate LTβ receptor and HVEM–BTLA pathways form an integrated signaling circuit. Targeting these cytokine pathways with specific antagonists (antibody or decoy receptor) can alter lymphocyte differentiation and activation. Alternately, agonists directed at their cell surface receptors can restore homeostasis and potentially reset immune and inflammatory processes, which may be useful in treating autoimmune and infectious diseases and cancer.