In vitro production of interleukin-1 receptor antagonist in IgG- mediated red cell incompatibility

BACKGROUND: Recently, proinflammatory cytokines including interleukin 1 (IL-1) have been implicated in the pathophysiology of immune-mediated hemolysis. Little is known, however, about the mechanisms by which inflammatory events in these reactions may be downregulated. IL-1 receptor antagonist (IL-1ra) inhibits the actions of IL-1 by competition for cellular receptors, and thus it may regulate the biologic actions of IL-1 during immune-mediated hemolysis. The production of IL-1ra by peripheral blood mononuclear cells (PBMNCs) in response to IgG-coated red cells in vitro was investigated. STUDY DESIGN AND METHODS: Fresh PBMNCs were obtained by density gradient separation of heparinized whole blood. PBMNCs were cultured in the presence of anti-D-coated, Rh-positive red cells or uncoated Rh- negative red cells under nonadherent conditions. IL-1ra concentrations in the culture media were measured by enzyme-linked immunosorbent assay. IL-1ra and IL-1 beta gene expression was assessed by Northern blot analysis of PBMNC mRNA. RESULTS: IL-1ra production was evident 4 hours after stimulation with IgG-coated red cells and increased progressively over 24 hours. Gene expression of IL-1ra was first detected at 2 hours, lagging behind that of IL-1 beta. IL-1ra gene expression was not inhibited by neutralizing polyclonal antibodies to IL-1. Immunocytochemical staining to determine the cellular source localized IL-1ra production to monocytes engaged in erythrophagocytosis. IL-1ra production was inhibited by dexamethasone (10(-7) M). CONCLUSION: These results suggest that IL-1ra production may partly account for the variable pathophysiologic events seen in IgG- mediated autoimmune hemolysis and hemolytic transfusion reactions. Steroid treatment may also downregulate anti-inflammatory cytokine production in immune hemolysis.     

椎间盘镜髓核摘除术后并发症30例的原因及防治措施

0引言近几年来,后路脊柱显微内镜在脊柱外科领域中的应用得到了迅速发展,并逐渐成为治疗腰椎间盘突出症的主流趋势,其综合疗效优于传统开放手术[1].     

天花粉蛋白诱发人体免疫抑制的遗传控制——Ⅲ.HLA-DQA1和DQB1基因的顺式和反式互补作用

根据天花粉蛋白（Tk）作用了淋巴细胞体外增殖的抑制是否由CD8细胞所介导,健康人群被分成介导型（M~+）和非介导型（M~-）两类。我们已有的工作证明,性状M~+/M~-由HLA连锁的一对孟德尔基因控制。本文采用分子生物学手段,对M~+”和M~-个体作HLAⅡ类基因的精细分型,发现编码DQ异二聚体分子的DQA和DQB两个基因同时决定M~+的表达,而且等位基因DQA1*0501和DQB1*0201以顺式和反式两种形式发挥互补作用,从而把人体中调控Tk免疫应答的遗传成份直接定位在该特定DQ分子的编码基因上。这一互补现象同时解释了DR3、DR5和DR7与M~+呈现次级关联的复杂格局。     

尼古丁舌下含片用于戒烟115例临床分析:多中心随机双盲安慰剂对照试验

目的:通过尼古丁舌下含片用于戒烟的随机双盲安慰剂对照的临床验证,评价尼古丁舌下含片用于戒烟的有效性及安全性。方法:①纳入对象240例来源于和平里医院所属社区卫生服务站(为2006-04/12广告招募所收集),均为尿可的宁检测呈阳性的吸烟患者240例,其中安慰剂组120例、尼古丁舌下含片组120例;年龄18～65岁。纳入者均有1年以上吸烟史,每日吸烟10支以上(含10支),并至少有过一次戒烟失败史,且均对试验目的知情同意。②尼古丁舌下含片组采用尼古丁舌下含片(北京泽生生物技术研究所研制,活性成分是尼古丁)进行干预。给药方法为替代递减给药方案,剂量根据FTND(Fagerstrom烟碱依赖量表)分值确定(FTND≥7分者为重度依赖),治疗范围为0～20片/d;安慰剂组:给予口服淀粉制备的安慰剂。两组均干预8周,指标观察至停药后4周。③以戒烟成功率、吸烟量减少情况、CO呼出量评估疗效。安全性评价依据不良事件、心电图、实验室检查、生命体征和体格检查等。④疗效比较采用配对t检验、组间t检验或秩和检验。副反应频度和严重程度比较采用χ2检验。结果:两组各115例进行疗效和安全性评价。疗效:①戒烟成功率与有效率:安慰剂组于治疗结束时戒烟成功率和戒烟总有效率分别为19.1%和57.4%,低于尼古丁舌下含片组(52.2%,85.2%)。②CO呼出量:两组在治疗开始时和治疗第4天比较,差异无显著性意义,以后至实验结束时比较,差异均有显著性意义(P<0.05)。服药安全性:尼古丁舌下含片不良反应轻,局部和全身的不良反应随药物使用时间的延长而逐渐减轻,适于长期服用。结论:①尼古丁舌下含片用于戒烟的疗效明显优。②尼古丁舌下含片的不良反应轻,耐受性好,是有效、安全的戒烟药物。     

Detection of human herpesvirus-8 DNA in oral ulcer tissues of HIV-infected individuals

OBJECTIVE: To determine the frequency of detection of human herpesvirus-8 (HHV-8) in HIV-related oral ulcers. DESIGN: Analysis of archived biopsy material. METHODS: Nested polymerase chain reaction of DNA extracts. RESULTS: HHV-8 DNA was detected in six of 10 oral ulcers of HIV-positive patients without oral Kaposi's sarcoma (KS) lesions and five of 11 oral KS lesions. The positive non-KS samples were derived from various oral sites. CONCLUSIONS: In HIV-positive people, HHV-8 can infect oral tissues that are not affected by KS.     

Halitosis and periodontal disease in subjects with mental disabilities

Objective:  The aim of this study was to investigate the relationship between halitosis, presence of N -benzoyl-DL-arginine-2-naphthylamide (BANA) positive activity (indicative of Treponema denticola , Porphyromonas gingivalis , Tannerella forsythensis ) and periodontal conditions in subjects with mental disabilities.
Materials and methods:  The population consisted of 17 Down syndrome (DS), 17 mentally retarded (MR) and 17 mentally healthy subjects (MH) – control group. A portable sulfide monitor was used to measure the concentration of volatile sulfur compounds (VSC) found in the mouth. Clinical parameters [Plaque Index (PlI), Probing Depth (PD), Bleeding on Probing (BOP)] were obtained from six reference teeth. Subgingival plaque samples for BANA Test were taken from the same six teeth and dorsum of the tongue.
Results:  PlI and BOP were higher in DS than in MR and MH, respectively ( P  < 0.05). Mean PD was similar between DS and healthy groups but it was higher than the MR group. No significant differences were found among the three groups regarding the presence of BANA positive species, however the VSC levels were significantly lower in DS (97.23 ppb) than in MR (203.23 ppb) and MH individuals (180.53 ppb).
Conclusions:  Even though the presence of BANA positive activity was similar among DS, MR and MH subjects, halitosis seemed to be lower in the DS group.     

P8 Halitosis and periodontal disease in subjects with mental disabilities

Patients with complaints of halitosis do seek treatment from physicians and dental practitioners, because of the fear that their halitosis may interfere with their social activities. Although the prevalence of halitosis has been reported to be as high as 50%, most physicians and dental practitioners are poorly informed about the causes and treatments of halitosis. In order to care for patients with complaints of halitosis a multidisciplinary team was established at the Erasmus Medical Centre, Rotterdam, The Netherlands. The team included a dental hygienist, an otorhinolaryngologist, and a dentist, who developed a special halitosis programme. One short press release regarding the establishment of the team, was provided to the national press-centre. In the out-patient clinic more than 700 patients were seen by the team. Using a structured questionnaire fed to a PC, patients answered questions regarding complaints about the oral cavity, the upper respiratory tract, the throat, their general health, their cleansing habits of the oral cavity, and prior experiences with general physicians, dental practitioners, and medical specialists. They underwent examinations of the extent of their halitosis, of the perioral and neck region, the oral cavity, the upper respiratory tract, and the upper digestive tract. Finally, the members of the team came to a joint diagnosis and a joint treatment plan for every individual patient. Of the first 700 consecutive patients 57% were women. More than 80% were between 20 and 59 years old. One-third reported that they were never having breakfast or ate only soft food in the morning. Only 2% were diagnosed as having chronic sinusitis, 11% as having pharyngitis, 3% as having laryngitis, and 3% as having tonsillitis.     

cDNA cloning and chromosome mapping of the human Fe65 gene: interaction of the conserved cytoplasmic domains of the human beta-amyloid precursor protein and its homologues with the mouse Fe65 protein

Using the yeast two hybrid system, a mouse embryo cDNA library was screened for proteins that interact with the C-terminus of the human beta-amyloid precursor protein (beta PP). A fusion protein was identified that interacts specifically with the cytoplasmic domain of beta PP and does not interact with the beta-amyloid region. The protein encoded by this partial mouse cDNA is identical to the C-terminus of the rat Fe65 protein. This mouse protein also interacts with the homologous C-terminal domains of the mouse amyloid precursor-like proteins, APLP1 and APLP2. These conserved cytoplasmic regions contain a common amino acid motif, Asn-Pro-Thr-Tyr, which has previously been shown to influence both the secretion and internalization of beta PP. Fe65 has been implicated in regulatory and cell signaling mechanisms because it contains two different motifs involved in protein binding, a WW domain (a variant of Src homology 3 domains) and a phosphotyrosine interaction domain (PID). Interestingly, the PID domain binds to the same motif present in the conserved cytoplasmic domains of the beta PP and beta PP-like proteins. RNA analyses reveal that Fe65 is predominantly expressed in brain and in the regions most affected by Alzheimer's disease (AD)-associated neuropathology. The human Fe65 mRNA was cloned from a fetal brain cDNA library. The message encodes a protein of 735 amino acids that is 95% identical to the rat Fe65 protein. The human Fe65 gene was mapped on human metaphase chromosomes to band 11p15 using fluorescence in situ hybridization.      

BRCA2 alteration is important in clear cell carcinoma of the ovary

BRCA2 has been shown to play a significant role in hereditary ovarian carcinoma. Several cases of clear cell carcinoma (CCC) of the ovary containing BRCA2 mutations have been identified. We hypothesize that sequence variants of the BRCA2 gene are common in CCC of the ovary. Multiple methods were utilized to detect BRCA2 genetic alterations in a cohort of 13 ovarian CCC. These included an LOH analysis for copy number, real-time and methylation-specific polymerase chain reaction (PCR) to probe for BRCA2 promoter methylation, in addition to protein truncation testing (PTT) gel screening for nonsense BRCA2 mutations, and finally direct gene sequencing to either confirm the nonsense mutations or to detect candidate missense mutations in the remaining tumor samples. Whenever a sequence variation was detected in a tumor sample, the corresponding region was sequenced from a blood sample to determine germline status. Seven BRCA2 sequence variations were identified in 6 of the 13 CCC (46%); three tumors contained an alteration in BRCA2 copy number. Only one subject carried a germline sequence variation that might alter BRCA2 function despite the fact that a family history of breast, ovarian or colon cancer was common in this population. The 5-year disease-specific survival probability for patients with a BRCA2 alteration is 87.5%, compared to only 40% for those patients without a BRCA2 alteration ( p = 0.39).
Alterations in BRCA2 gene sequence, copy number, or expression are extremely common in CCC and may contribute to a paradoxical better clinical outcome.