Lupus autoantibodies discriminate between the highly homologous Sm polypeptides B/B' and SmN by binding an epitope restricted to B/B'.

The ubiquitous Sm polypeptides B/B' (28 and 29 kD) and the highly homologous tissue-specific Sm N polypeptide (29 kD) share several autoepitopes recognized by systemic lupus erythematosus (SLE) sera. Previous studies on the antigenicity of nuclear antigens recognized by human autoantibodies have not discriminated between ubiquitous and tissue-specific forms. We set out to examine whether a tissue-specific nuclear antigen, Sm N, is autoantigenic in SLE by comparing the immunoreactivity of the most unique sequences in this polypeptide. Synthetic peptides from the two regions of least sequence homology that occur between Sm N and Sm B/B', a dodecamer (amino acid residues 179-190 containing five substitutions) and an undecamer (residues 203-213 containing four substitutions) were coupled to a carrier protein. These conjugates were used to quantify IgG anti-peptide antibodies in sera from patients with SLE. Of 43 sera with anti-Sm specificity, six bound to the B/B' 179-190 peptide but not to the N version. None of 17 anti-Sm-negative SLE sera bound these peptides. The second region of least sequence homology between N and B/B' (203-213) was not antigenic. Our data suggest that a subset of SLE patients with anti-Sm reactivity have IgG autoantibodies capable of discriminating between Sm N and SmB/B' polypeptides by binding a previously unreported SmB/B'-specific autoepitope. The data also indicate that brain and heart-specific anti-Sm antibodies do not exist in SLE sera, suggesting that these tissues do not participate in the induction or maintenance of the autoimmune anti-Sm response.     

Bilateral receptive fields of cells in rat Sm1 cortex

Summary Single cells in the primary somatosensory (Sm1) cortex were investigated for responses to bilateral hindpaw stimulation in Wistar rats anaesthetised by continuous intravenous administration of Althesin. Fifty-one percent of cells sampled (N = 134) responded to equivalent punctate mechanical stimuli delivered to both the contralateral and ipsilateral hindpaws under light anaesthesia. The distribution by cortical depth of cells with receptive fields (RFs) on both hindpaws was not significantly different from cells which had only contralateral RFs. No cell was found with a purely ipsilateral RF. For 86% of cells tested (N=44) the ipsilateral RF was partly or completely homologous with areas within the contralateral RF. The sizes of ipsilateral RFs were smaller on 66% of occasions when tested against their contralateral RFs. Modal latencies to ipsilateral mechanical stimulation were longer than to contralateral stimulation (34.1±9.1 ms (S.D) cf. 26.4±7.2 ms, N=44). Ipsilateral RFs were lost for 77% of cells tested following a 33% increase in anaesthetic infusion rate. Conditioning mechanical stimuli applied to the centre receptive field (CRF) on the ipsilateral hindpaw reduced or abolished a cell's responses to equivalent test stimuli applied to it's contralateral CRF with C-T intervals of 20–200 ms. Conditioning stimuli applied to the CRF contralateral to the cell reduced or abolished responses to test stimuli on the cell's ipsilateral CRF using C-T intervals of 0–900 ms. Responses in one cortex to stimulation of the ipsilateral hindpaw were unaffected by elimination of responses from the same hindpaw in the opposite contralateral Sm1 cortex, where responses had been suppressed by topical Lignocaine administration. Retrograde transport of horseradish peroxidase from hindpaw Sm1 cortex labelled many cells in homolateral thalamus, but failed to label cells in the entire forebrain contralateral to the injection site. It is concluded that direct crossed thalamocortical and callosal Sm1-Sm1 pathways do not contribute to the production of hindpaw ipsilateral receptive fields.     

The biodistribution and Kinetics of the Samarium-153 labeled avidin, streptavidin and biotin

Theextraordinaryhighaffinityofavidin(Av)andstrepavidin(SA)forbiotin(Bt)hasbeenutilizedinpretargetingtechniquefordeliveringradiolabeledbi-otinderivativessuitableforimagingandtherapytotarget-boundstreptavidin-oravidin-conjugatedmono-clonalantibodies(mAb).Preliminaryreportsusingthistechniquehavebeenavailableinbothexperimen-talandclinicaltrials,andmuchsuccesshasbeenachieved[1－3].However,questionsremainpertainingtothepharmacokineticsandbiodistributionofradiola-belledSAandAvinmice,andtherolesoft…     

~(153)Sm-EDTMP联合~(99m)Tc亚甲基二膦酸盐治疗多发性骨转移癌的临床观察

目的　评价 1 53钐 -乙二胺四亚甲基膦酸盐 (1 53Sm- EDTMP)与 99m Tc亚甲基二膦酸盐 (商品名云克 )联合应用治疗多发性骨转移癌的疗效。方法　各种骨转移癌 132例 ,随机分组治疗 ,第 1组 4 2例患者仅静脉注射 1 53Sm- EDTMP,1.0× 10 7Bq/ kg,第 2组 5 0例患者 1 53Sm- EDTMP联合 99m Tc亚甲基二膦酸盐治疗 ,1 53Sm- EDTMP用量不变 ,并与静脉注射 1 53Sm- EDTMP后的第 5天开始用 99m Tc亚甲基二膦酸盐连续 5 d。第 3组 4 0例患者静脉滴注博宁 ,10 d1个疗程。结果　第 1组镇痛有效率为 6 1% ,疼痛缓解持续时间平均 4周。第 2组联合用药组镇痛有效率达 80 % ,疼痛缓解持续时间平均 8周。第 3组镇痛有效率 4 2 % ,疼痛缓解持续时间平均 2周。 3组疗效有显著统计学意义 (P<0 .0 5 )。结论　不论 1 53Sm - EDTMP单独使用还是与 99m Tc亚甲基二膦酸盐联合用药都是治疗多发骨转移的有效止痛方法 ,相比之下 ,联合用药可明显提高镇痛效率。     

Deleting the BAFF receptor TACI protects against systemic lupus erythematosus without extensive reduction of B cell numbers

B cell-activating factor of the TNF family (BAFF) is an essential B cell survival factor. However, high levels of BAFF promote systemic lupus erythematosus (SLE) in mice and humans. Belimumab (anti-human BAFF) limits B cell survival and is approved for use in patients with SLE. Surprisingly, the efficacy of rituximab (anti-human CD20) in SLE remains controversial, despite depleting B cells more potently than belimumab. This raises the question of whether B cell depletion is really the mechanism of action of belimumab. In BAFF transgenic mice, SLE development is T cell-independent but relies on innate activation of B cells via TLRs, and TLR expression is modulated by the BAFF receptor TACI. Here, we show that loss of TACI on B cells protected against BAFF-mediated autoimmune manifestations while preserving B cells, suggesting that loss of BAFF signaling through TACI rather than loss of B cells may underpin the effect of belimumab in the clinic. Therefore, B cell-sparing blockade of TACI may offer a more specific and safer therapeutic alternative to broad B cell depletion in SLE.     

Serum SmD autoantibody proteomes are clonally restricted and share variable-region peptides

Recent advances in mass spectrometry-based proteomic methods have allowed variable (V)-region peptide signatures to be derived from human autoantibodies present in complex serum mixtures. Here, we analysed the clonality and V-region composition of immunoglobulin (Ig) proteomes specific for the immunodominant SmD protein subunit of the lupus-specific Sm autoantigen. Precipitating SmD-specific IgGs were eluted from native SmD-coated ELISA plates preincubated with sera from six patients with systemic lupus erythematosus (SLE) positive for anti-Sm/RNP. Heavy (H)- and light (L)-chain clonality and V-region sequences were analysed by 2-dimensional gel electrophoresis and combined de novo database mass spectrometric sequencing. SmD autoantibody proteomes from all six patients with SLE expressed IgG1 kappa restricted clonotypes specified by IGHV3-7 and IGHV1-69 H-chains and IGKV3-20 and IGKV2-28 L-chains, with shared and individual V-region amino acid replacement mutations. Clonotypic sharing and restricted V-region diversity of systemic autoimmunity can now be extended from the Ro/La cluster to Sm autoantigen and implies a common pathway of anti-Sm autoantibody production in unrelated patients with SLE.     

胞嘧啶的153Sm标记及其用于肿瘤体内显像的可行性

目的 探讨利用放射性核素153Sm体外标记胞嘧啶进行肿瘤代谢显像的可行性.方法 胞嘧啶与DTPA的偶联产物C-DTPA,经纯化后体外标记153Sm,并对得到的显像剂C-DTPA-153 Sm的质量规格进行检测:①制剂要求:检菌,热原检测;②毒理学:急性毒理测定;③特殊参数:标记率,体外稳定性;④药动学:家兔血浆药物代谢动力学;⑤药效学:体外细胞显像,荷瘤小鼠显像.结果 体外实验、动物实验显示C-DTPA-153Sm为无菌、无热原、无毒性的安全制剂,并且可以在肿瘤部位浓集.结论 153Sm标记胞嘧啶代谢显像方法对多种肿瘤有诊断价值,可以无创性的体内评价肿瘤的增生状态,具有重要的临床应用价值.     

A multivalent chimeric vaccine composed of Schistosoma mansoni SmTSP‐2 and Sm29 was able to induce protection against infection in mice

Schistosoma mansoni is a blood fluke parasite responsible for schistosomiasis. The best long‐term strategy to control schistosomiasis is through immunization combined with drug treatment. In this study, we cloned, expressed and purified SmTSP‐2 fused to the N‐ and C‐terminal halves of Sm29 and tested these chimeras as vaccine candidates using an adjuvant approved to be used in humans. The results demonstrated that vaccination with SmTSP‐2 fused to N‐ or C‐terminus of Sm29‐induced reduction in worm burden and liver pathology when compared to control animals. Additionally, we detected high levels of mouse‐specific IgG, IgG1 and IgG2a against both chimeras and significant amounts of IFN‐γ and TNF‐α and no IL‐4. Finally, studies with sera from patients resistant to infection and living in schistosomiasis endemic areas revealed high levels of specific IgG to both chimeras when compared to healthy individuals. In conclusion, SmTSP‐2/Sm29 chimeras tested here induced partial protection against infection and might be a potential vaccine candidate.     

从骨碎补中制备新北美圣草苷和柚皮苷对照品的研究

目的 建立从骨碎补中制备新北美圣草苷和柚皮苷对照品的方法.方法 结合大孔树脂富集、硅胶柱色谱、中性氧化铝吸附、Sephadex LH-20柱色谱和重结晶方法对骨碎补乙醇提取物进行分离纯化,通过MS、IR、UV、1H-NMR和13C-NMR进行结构鉴定.结果 制备得到的新北美圣草苷和柚皮苷质量分数分别为99.5 %、99.3%.结论 建立的制备方法简单,对照品质量分数高,可作为骨碎补药效物质基础研究和骨碎补药材质量控制的对照品.     

153钐-乙二胺四亚甲基膦酸治疗骨转移瘤的疗效观察

目的：观察^153钐-乙二胺四亚甲基膦酸（^153钐-EDTMP）治疗骨转移瘤的疗效。方法：对96例骨转移瘤患者给予剂量范围为18．5～55．5MBq／kg的^153钐-EDTMP治疗。结果：患者疼痛总缓解率为86．5％（83／96）；影像学显示部分患者骨转移灶缩小、消失、减少或病灶处浓聚减弱。不良反应主要为骨髓抑制，经治疗2周～4周内皆能好转恢复。结论：^153钐-EDTMP对转移性骨肿瘤有明显缓解骨痛、控制病情进展的作用，使用安全。