Phage-displayed mimotopes recognizing a biologically active anti-HIV-1 gp120 murine monoclonal antibody

Antibody-dependent cellular cytotoxicity (ADCC) is a host defense mechanism in which Fc receptor-bearing effector cells in combination with antigen-specific antibodies recognize and kill antigen-expressing target cells. The authors previously described a murine monoclonal antibody (MAb-ID6) that mediated ADCC activity against HIV-infected cells. It was demonstrated that the specificity of MAb-ID6 maps to the first 204 amino acids of gp120; however, the exact epitope was not identified. In the present work, by screening phage display libraries with MAb-ID6, the authors have mapped the corresponding epitope to amino acids 86-100 (HIV-1 gp120 sequence). This epitope lies within the C1 region of gp120 and is highly conserved among all subtypes and circulating recombinant forms of HIV-1. Thus, these phage mimotopes of C1 may serve as components of a vaccine for the induction of gp120-specific antibodies mimicking MAb-ID6.     

Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis

Osteopenia and osteoporosis are well-known complications detected in celiac disease patients with still obscure pathogenesis. In the present study we investigated the presence of circulating anti-bone autoantibodies in patients with celiac disease and explored their role in the associated bone disease. We evaluated serum samples from 33 patients at the time of diagnosis and from 20 of them after treatment. Sera from patients with inflammatory bowel disease (n = 9), nonceliac osteoporotic (n = 18), and healthy individuals (n = 10) were used as controls. The presence of IgA specific anti-bone antibodies was first investigated using indirect immunofluorescence on cryosections of fetal rat tibia (20-day pregnancy). Furthermore, samples were homogenized and total tissue extracts were subjected to Western blot analysis to confirm immunoreactivity. At diagnosis, sera from 51.5% (17/33) of celiac patients had antibodies that recognized antigenic structures in chondrocytes and the extracellular matrix along mature cartilage, bone interface, and perichondrium of fetal rat bone. Among controls, only two osteoporotic patients showed very low titles of anti-bone autoantibodies. The immunostaining was localized in areas where an active mineralization process occurred and was similar to the distribution of the native bone tissue transglutaminase. The frequency of patients with positive baseline titers of anti-bone antibodies diminished significantly after treatment (P = 0.048). Western blot assays confirmed the presence of autoantibodies in sera from patients with a positive immunofluorescence staining. Autoantibodies recognized a major protein band on tissue extracts with a molecular weight of 77–80 kDa, which could be displaced when sera were preadsorbed with human recombinant tissue transglutaminase. We provide original evidence that patients with celiac disease have IgA-type circulating autoantibodies against intra- and extracellular structures of fetal rat tibia. Our findings suggest that these antibodies recognize bone tissue transglutaminase as the autoantigen, and based on the localization of the immunoreactivity we speculate that they might have an active role in the pathophysiology of celiac disease-associated bone complications.     

Genetic Conservation of Hemagglutinin Gene of H9 Influenza Virus in Chicken Population in Mainland China

The hemagglutinin (HA) genes of 12 H9N2 influenza virus strains isolated from chickens in Mainland China during the period 1995–2002 were genetically analyzed. All the isolates possessed the same amino acid motif -R-S-S-R/G-L- at the cleavage site of HA. Except for the conserved amino acids, as is the case in the other avian influenza viruses, located in the receptor binding site, all of the 12 isolates possessed N at amino acid position 183; A, T, or V at position 190; K at position 137, whereas the representative strains of the other lineage (except Dk/HK/Y280/97-like lineage) virus of H9N2 viruses had H, E, and R at these positions respectively. These could be considered as the partial molecular markers of the H9 viruses isolated from chickens in Mainland China. Phylogenetic analyses showed HA genes of these isolates belonged to that of A/duck/Hong Kong/Y280/97-like virus lineage. No A/quail/Hong Kong/Gl/97-like virus was found in chicken, population since the outbreak of H9N2 influenza in Mainland China in 1992. The available evidence indicates that HA genes of H9 influenza virus circulating in Mainland China during the past years were well conserved.     

Influence of food on the intravenous and oral dose kinetics of propranolol in the dog

The intravenous and oral dose kinetics of propranolol were studied in the dog both in a fasted state and immediately after a meal consisting of 100 g of cooked beef liver. Fifty Ci of³H-propranolol was administered intravenously simultaneously with a 40-mg oral dose of unlabeled propranolol. Plasma³H-propranolol was measured by specific extraction and liquid scintillation spectrometry, and unlabeled plasma propranolol was determined by gas chromatography-mass spectrometry. Feeding significantly reduced (25%) the elimination half-life and increased (52%) the systemic clearance of intravenous propranolol. The increase in the systemic clearance of propranolol after feeding was mostly due to an increase (60%) in apparent hepatic blood flow, which appeared to remain elevated for 5–7 hr. The meal had no influence on the apparent volume of distribution or plasma binding. Feeding did not affect the area under the concentration-time curve of oral propranolol, but significantly delayed the rate of oral propranolol absorption, shifting the time to reach peak plasma levels from 60 to 158 min. The results of this study suggest that feeding alters the disposition of propranolol in the dog by producing a sustained increase in hepatic blood flow.This work was supported by National Institute of Health grants GM 07534, GM 20387, and HL 29566.     

催经止孕药Ru-486的临床药代动力学

应用高效液相色谱法(HPLC)研究了抗孕激素药,Ru-486的临床药代动力学。六名志愿受试者,一次口服Ru-486 50毫克后测得该药的药代动力学各项参数,血药半寿期t 1/2 33.0小时,一级消除速率常数Kel 0.021 hr~(-1),血药表观容积Vd 120.1 Liter,体内血药总廓清率Cl2.5 Liter/hr,药-时曲线下面积Auc 19825.1 ng/ml/hr。实验表明,服药后一小时血药浓度迅即达高峰,随后转入消除期,血浆药物浓度在消除相的头4～8小时消除较快,而后逐渐减慢,持续24小时,到48小时血药浓度已较低(0.15±0.07μg/ml)。     

上海市预防接种工作人员疑似预防接种异常反应监测认知和报告影响因素

目的了解上海市预防接种工作人员疑似预防接种异常反应(Adverse events following immunization,AEFI)监测的知识和态度以及影响AEFI报告的因素。方法采用方便抽样在上海市所有459个预防接种门诊选择预防接种工作人员开展问卷调查,分析AEFI监测知识得分(满分6分)和态度,采用多因素Logistic回归分析AEFI报告的影响因素。结果1379名调查对象的AEFI监测知识平均得分为3.30±1.31分;认为开展AEFI监测有必要、报告AEFI是自身职责、AEFI监测是额外工作负担的调查对象分别占98.84%、92.75%、30.38%。69.62%的调查对象近1年报告过AEFI;社区接种门诊、免疫规划专职人员、近1年接受过AEFI培训、AEFI监测知识得分高的调查对象报告AEFI的比例高[OR(95%CI):19.55(14.16-26.98)、1.95(1.45-2.64)、3.14(1.76-5.59)、1.91(1.38-2.63)]。结论上海市预防接种工作人员AEFI监测知识水平不高,对AEFI监测存在一定认识误区;需加强AEFI监测培训,进一步提高其AEFI报告意识。     

对河南荥阳青台遗址人骨骨病的研究

目的 :了解荥阳青台遗址人骨疾病的情况。方法 :用观察、测量和X线投射方法进行研究。结果 :在 2 7例骨架中发现骨性产道和骶骼关节骨性融合异常 1例、脊柱唇样增生 4例、胫骨慢性骨髓炎 1例。结论 :在考古中发现骨性产道异常伴骶髂关节骨性融合。难产属首次报导。将该病病史向前推进约 6 0 0 0多年。     

肝肺综合征的X线表现

目的：探讨肝肺综合征的X线表现。方法：对18例肝肺综合征（Hepato pulmonary Syndrome,HPS)胸部平片进行了回顾性分析,其中3例行CT扫描。结果：胸部异常16例,X线表现为肺纹理增多、紊乱,其中14例下肺呈结节状阴影,4例伴有斑片状阴影;4例伴有胸腔积液;2例伴有下肺盘状肺不张。3例胸部CT显示病变较平片更多、更清晰。结论：肺基底部结节状阴影是HPS典型X线表现,但不具有特异性。     

文冠果果壳中两种甾醇成分的结构研究

目的：首次研究文冠果果壳的化学成分。方法：采用柱色谱和光谱方法。结果：从文冠果果壳中分得2种甾醇,经鉴定为：（3β,5α,20R,24S）－豆甾－7,反－22－二烯－3－醇和（3β,5α,20R,24R）-豆甾－7－烯－3－醇。结论：2种甾醇在文冠果中均为首次分得。