An anti-EnaTS detected in the serum of an MiI homozygote

The serum of EH reacted with all red cells (RBCs) except her own, ficin- or trypsin-treated red cells, and En(a-) red cells. This reactivity defined an anti-EnaTS specificity. The red cells of the proposita typed as M-N+S-S+, Vw+Mur-Hil-Hut-Anek-Lane-, Wr(a-b+), EnaKT+. Red cells of five relatives were Vw+ and positive with her serum. Titration studies suggest that EH is genetically an MiI homozygote and that her Vw+ relatives are MiI heterozygotes. There is no history of consanguinity. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis and immunoblotting studies have agreed with the serologic observations. A variant sialoglycoprotein of faster mobility than normal glycoprotein A, but no normal glycoprotein A, was detected on her red cells. Treatment with N-glycanase did not alter the mobility, which indicated that there was no N-glycosylation of residue 26. These findings are in agreement with the reported properties of the Mi.I-specific glycoprotein A. The relatives' Vw+ red cells showed the variant sialoglycoprotein and normal glycoprotein A. EH appears to be the first reported MiI homozygote.     

Time-dependent loss of surface complement regulatory activity during storage of donor blood

The survival of transfused red cells (RBCs) diminishes with time of in vitro storage in blood banks, but the molecular mechanisms underlying the slow but incessant deterioration are incompletely understood. To investigate the possibility that impaired resistance to autologous complement attack could play a role in this phenomenon, packed RBCs stored for variable periods were assayed for decay-accelerating factor (DAF) and CD59, two glycoinositol-phospholipid (GPI)-anchored, membrane- associated complement regulatory proteins that function physiologically to protect blood cells from autologous complement activation on their surfaces. Immunoradiometric and flow cytometric assays employing DAF and CD59 monoclonal antibodies showed that levels of both surface proteins gradually declined over 6 weeks. Digestion analyses with phosphatidylinositol-specific phospholipase C, an enzyme that releases GPI-anchored proteins from cell surfaces, showed that DAF and CD59 molecules with GPI anchors containing unacylated inositol were preferentially lost. These findings suggest: 1) that DAF and CD59 molecules with acylated GPI anchors are more stable in RBC membranes than are molecules with unacylated GPI anchors, and 2) that DAF and CD59 loss may participate with other membrane alterations that occur during in vitro storage in compromising the survival of transfused cells.     

转脑啡肽基因移植细胞微囊化对大鼠慢性周围神经损伤的镇痛作用

目的：观察微囊化转大鼠脑啡肽原基因（pENK）细胞移植对慢性脊神经压榨性损伤大鼠的镇痛效应. 方法：实验于2006-03/2007-04在郑州大学医学重点实验室完成.①实验方法：通过反转录-聚合酶链反应技术可获得大鼠pENK基因,Hind Ⅲ,ClaⅠ双酶切后,同相应双酶切的pLNCX2载体大片段连接,构建成pENK基因反转录病毒载体pLNCX2-Enk,然后用脂质体法将该载体转染PT67细胞,G418筛选,获得携带pENK基因高滴度反转录病毒产毒细胞系.用海藻酸钠-多聚赖氨酸-海藻酸钠微囊包埋后,进行体外培养,定期检测微囊化细胞活性和pENK分泌量变化.同时,将转基因细胞移植于慢性脊神经压榨性损伤大鼠的蛛网膜下腔.②实验分组：SD大鼠60只,其中53只按照Bennett和Xie法制作大鼠慢性左侧坐骨神经压迫性损伤模型,其中42只造模成功.术后1周,将动物按随机数字表法分为3组,每组16只：微囊化转基因细胞移植组、空囊移植组和阴性对照组.微囊化转基因细胞移植组、空囊移植组分别植入微囊化细胞悬液80 μL（约300个微囊）、空微囊悬液80 μL（约300个空囊）,阴性对照组不注射任何悬液.③实验评估：术后2周和8周行甲醛实验,在大鼠一侧后爪掌侧皮下注射体积分数为0.05的甲醛50 μL,观察其注射后1 h内的痛反应.采用Abbott等所推荐的以缩腿及舔爪时间之和作为行为学反应的指标.注射甲醛后,立即记录大鼠1 h内每5 min的缩腿及舔爪时间. 结果：①术后2周甲醛实验：空囊移植组第一时相的急性痛阶段（注射后5 min）和第二时相的慢性痛阶段（注射后41～45 min）大鼠的缩腿及舔爪时间都少于微囊化转基因细胞移植组（P＜0.01）.而在静息期,3组大鼠的缩腿及舔爪时间差异无显著性意义（P＞0.05）.②术后8周甲醛实验：3组大鼠的痛觉行为都呈明显的双时相反应.除了静息期（注射后5～15 min）,微囊化转基因细胞移植组在各时间点上大鼠的缩腿及舔爪时间均低于空囊移植组（P＜0.05）.微囊化转基因细胞移植组大鼠的缩腿及舔爪时间在第一时相的急性痛阶段和第二时相的慢性痛阶段都低于空囊移植组（P＜0.05）. 结论：微囊化转pENK基因细胞移植对慢性神经痛大鼠有一定的镇痛作用,有望成为运动员慢性疼痛治疗的新方法.     

Demographic characteristics and prevalence of serologic markers among donors who use the confidential unit exclusion process: the Retrovirus Epidemiology Donor Study

BACKGROUND: Most blood centers utilize a confidential unit exclusion (CUE) process, intended to reduce the risk of transfusion-associated infectious diseases by allowing high-risk donors confidentially to exclude their blood from use for transfusion. The effectiveness of this method remains controversial. STUDY DESIGN AND METHODS: Confirmatory or supplemental test results for antibodies to human immunodeficiency virus, human T-lymphotropic virus type I, and hepatitis C virus, as well as hepatitis B surface antigen and syphilis and screening test results for antibodies to hepatitis B core (antigen) and alanine aminotransferase levels were obtained for approximately 1.8 million units donated during 1991 and 1992 at five blood centers within the United States. The prevalences of these infectious disease markers in units that the donors confidentially excluded (CUE+) and units that the donors did not exclude (CUE-) were calculated and examined within demographic subgroups. RESULTS: Units that were CUE+ were 8 to 41 times more likely to be seropositive for antibodies to human immunodeficiency virus and hepatitis C virus, hepatitis B surface antigen, and syphilis and three to four times more likely to react for antibody to hepatitis B core (antigen) or to have elevated alanine aminotransferase levels than units that were CUE- (p < 0.001). The positive predictive value of CUE (the percentage of CUE+ units that were confirmed seropositive for any marker) was 3.5 percent, and the sensitivity of CUE (the percentage of confirmed-seropositive units that were CUE+) was 2.3 percent. CONCLUSION: The current CUE process has low sensitivity and apparently low positive predictive value, and in many cases, it appeared that donors misunderstood it. Yet, CUE was not a “random process,” as CUE+ units were more likely to be seropositive for any infectious disease marker than CUE- units. This suggests that efforts to improve the CUE system may be warranted. As risk factors for transfusion-transmitted infection become more difficult to identify by history-based screening, however, such efforts may have limited effect.     

Commentary on “A novel treatment strategy for newly diagnosed high-grade T1 bladder cancer: Gemcitabine and cisplatin adjuvant chemotherapy—A single-institution experience.”

Background

Management of high-grade T1 (formerly T1G3) bladder cancer continues to be controversial. Should patients with T1G3 bladder cancer have an immediate radical cystectomy or should they receive intravesical bacillus Calmette-Guérin preserving bladder? Gemcitabine and cisplatin (GC) adjuvant chemotherapy may help to strike a balance between intravesical and early cystectomy. For purposes of this study, we continue to refer high-grade T1 lesion as “T1G3.”

Characterization of the epitope recognized by a monoclonal antibody highly specific for blood group M antigen

The mouse monoclonal antibody M2A1 of IgG1 class, which is highly specific for blood group M antigen, was obtained and characterized by means of hemagglutination, enzyme-linked immunosorbent assay, immunoblotting, and inhibition assays. The use of modified M glycoprotein preparations for inhibition tests and of variant McN and Henshaw red cell membranes for immunoblotting showed that M2A1 recognized an epitope including the NH2-terminal serine and sialic acid residues of glycophorin A, whereas the fifth glycine residue was not involved. The reactivity of the antibody with M antigen was distinctly dependent on ionic strength and pH; the optimum was at pH 8 to 9. The alpha-amino group of terminal serine residue was not necessary for the reaction with M2A1 antibody, and the results obtained suggested that the positive charge of this group contributed to decreasing antigen-antibody reactions at pH below 8. The reaction of the antibody with blood group N antigen was not detectable in any of the assays used.     

A study of confidential unit exclusion

The effectiveness of the confidential unit exclusion (CUE) procedure recommended by the Food and Drug Administration has been questioned by the blood banking community. The purpose of this study was to determine whether donors were informing the blood center correctly regarding the disposition (transfuse or do not transfuse) of their donated blood. A letter explaining the confidential study and requesting permission to send the participant a questionnaire noting his or her self-exclusion choice was mailed to 230 donors who had chosen transfuse and 276 donors who had chosen do not transfuse. After consent was obtained, participants were sent a second packet and asked to indicate whether they had chosen correctly and, if not, to identify reasons for that incorrect choice. A seven-word terminology quiz made up of words from the CUE form was also enclosed. All participants who had chosen transfuse indicated that this was the correct choice. Approximately 50 percent of those who had chosen do not transfuse indicated that this was an incorrect choice; the most common reason was that "I was not paying attention." The most frequently misunderstood term was "confidential." Donors who chose do not transfuse had a significantly higher rate of error on the terminology quiz (p less than 0.01) than did those who chose transfuse.     

Hospitalisation of and mortality from bleeding peptic ulcer in Sweden: a nationwide time-trend analysis

Aliment Pharmacol Ther 2011; 33: 578–584

Summary

Background Time‐trend analyses of incidence and mortality in bleeding peptic ulcer show divergent results. Aim To conduct a detailed national analysis of hospitalisation of and mortality from bleeding peptic ulcer in Sweden. Method Data from all hospitalisations at departments with primary responsibility for patients with bleeding ulcer in Sweden, with main diagnosis or co‐diagnosis of bleeding ulcer from 1987 to 2005 were retrieved from the Hospital Discharge Register. A validation study was performed due to an uncertainty in diagnostic setting after the introduction of ICD‐10 in 1997. Annual hospitalisation rates per 100 000 inhabitants in relation to gender, age and ulcer location were calculated as well as age‐standardised 30‐day mortality rates. Results Hospitalisations for bleeding ulcer decreased from 63.9 to 35.3 per 100 000 inhabitants per year during the study period. The decrease was greater among men (men: from 80.4 to 40.9; women: from 47.7 to 29.7) and in younger age groups. Bleeding gastric ulcer decreased in both genders, and bleeding duodenal ulcer decreased most among men, but was stable in a subgroup of elderly women. Median age increased from 70 to 76 years. Standardised 30‐day mortality increased from 5.3% to 6.2%. The increased mortality was found in those aged more than 65 years and with duodenal ulcer disease, whereas mortality remained unchanged in those with bleeding gastric ulcer. Conclusion Hospitalisation rates for bleeding peptic ulcer have markedly decreased in Sweden in all age groups. The 30‐day mortality is low compared with other nationwide studies in the western world, but has increased among patients with duodenal ulcer disease.     

The effects of sertindole on sensory gating, sensorimotor gating, and cognition in healthy volunteers

Sensory gating, indexed by P50 suppression, and sensorimotor gating, indexed by prepulse inhibition (PPI), are impaired in schizophrenia spectrum disorders. There is considerable evidence that schizophrenia patients treated with atypical antipsychotics exhibit relatively less gating deficits than do other patients with schizophrenia. Some recent studies have investigated the effects of antipsychotic medications on gating in healthy volunteers exhibiting low levels of gating, rather than in patients. Therefore, the current study investigated the influence of sertindole versus placebo in two separate experimental sessions, on PPI, P50 suppression, and cognition in 30 male volunteers stratified for low and high baseline gating levels. Sertindole increased PPI and P50 suppression in healthy subjects exhibiting low baseline PPI and low baseline P50 suppression, respectively, while sertindole attenuated gating in subjects exhibiting high baseline gating. Furthermore, subjects exhibiting low PPI chose worse strategies in a spatial working memory task. These findings suggest that mixed D(2)/5-HT(2) receptor antagonists enhance both PPI and P50 suppression in a way that enhances it in healthy subjects exhibiting low baseline gating. Furthermore, the results militate in favor of the concomitant assessment of PPI, P50 suppression and cognitive measures while investigating the effect of antipsychotic medication in healthy subjects.