Deoxycytidine kinase and deoxyguanosine kinase of Lactobacillus acidophilus R-26 are colinear products of a single gene

Three of the four deoxynucleoside kinases required for growth of Lactobacillus acidophilus R-26 exist as heterodimeric pairs specific for deoxyadenosine (dAK) and deoxycytidine (dCK) or dAK and deoxyguanosine (dGK). However, only two tandem genes, dak/dgk, are found, and are expressed only as dAK/dGK in transformed Escherichia coli. Sequencing peptides spanning 63% of the native dCK subunit revealed a sequence identical to that deduced from dgk (beginning MTVIVL···), except that dCK lacks residues 2 and 3 (dCK is M··IVL; dGK is ·TVIVL). Also, mass spectrometry indicates that native dCK and dGK subunits are identical in mass adjusted for the first three residues. Furthermore, the native enzymes have identical isoelectric pH values, indicating an equal number of charged residues. To enable E. coli to express peptide having the native dCK sequence, codons 2 and 3 were deleted from the dgk portion of the tandem genes, resulting in expression of protein having the specificities and regulatory properties of native dAK/dCK, including heterotropic stimulation of dAK activity by deoxycytidine or dCTP (not deoxyguanosine or dGTP) and end-product inhibition of the respective activities by dATP and dCTP. Subcloning normal and mutant dgk yielded homodimeric dGK and dCK, respectively. The dCK homodimer strongly resembles human dCK, with a low K_m for deoxycytidine, the ability to phosphorylate deoxyadenosine and deoxyguanosine at much higher K_m values, and end-product inhibition by dCTP. Thus two distinct and specific enzymes evidently are derived from a single Lactobacillus gene. The mechanism by which this occurs in vivo has yet to be elucidated.     

Thalidomide as salvage therapy for chronic graft-versus-host disease

Thalidomide has been reported to be an effective agent for treatment of chronic graft-versus-host disease (CGVHD). To determine the efficacy of this agent in patients with refractory CGVHD a total of 80 patients who failed to respond to prednisone (PSE) or PSE and cyclosporine (CSA) were treated with thalidomide. Sixteen patients (20%) had a sustained response, 9 with a complete remission and 7 with a partial response. Twenty-nine patients (36%) had thalidomide discontinued because of side effects, which included sedation, constipation, neuritis, skin rash, and neutropenia. Side effects were reversible with drug discontinuation except for mild residual neuritis in one case. Rashes and neutropenia have not previously been reported as thalidomide side effects when used for CGVHD treatment. We conclude thalidomide is immunosuppressive and active in the treatment of CGVHD. A high incidence of reversible side effects limited dose intensity and reduced the number of patients who could benefit from treatment.     

How to Increase Reach and Adherence of Web-Based Interventions: A Design Research Viewpoint

Nowadays, technology is increasingly used to increase people’s well-being. For example, many mobile and Web-based apps have been developed that can support people to become mentally fit or to manage their daily diet. However, analyses of current Web-based interventions show that many systems are only used by a specific group of users (eg, women, highly educated), and that even they often do not persist and drop out as the intervention unfolds. In this paper, we assess the impact of design features of Web-based interventions on reach and adherence and conclude that the power that design can have has not been used to its full potential. We propose looking at design research as a source of inspiration for new (to the field) design approaches. The paper goes on to specify and discuss three of these approaches: personalization, ambient information, and use of metaphors. Central to our viewpoint is the role of positive affect triggered by well-designed persuasive features to boost adherence and well-being. Finally, we discuss the future of persuasive eHealth interventions and suggest avenues for follow-up research.     

微核实验评价自制烤瓷合金的生物相容性

目的：通过微核实验检测自制Ni-Cr-Ti烤瓷合金对小鼠的致畸作用,评价其生物相容性. 方法：实验于2006-04/08在中国医科大学中心实验室完成.①实验分组：选择N1H纯系小鼠80只,按随机数字表法分为8组,每组10只：Ni-Cr-Ti合金组（剂量分别为0.02,0.002,0.000 2 mL/kg）、纯钛浸提液组（剂量分别为0.02,0.002,0.000 2 mL/kg）,阴性对照组（生理盐水）,阳性对照组（注射用环磷酰胺,75 mg/kg）.②实验方法：按50 mL/kg口服同剂量的浸提液,各组均于一次给药后24 h,麻醉后处死小鼠,取小鼠骨髓细胞.③实验评估：光镜下计数1 000个嗜多染红细胞的微核细胞数,并计数嗜多染红细胞与正红细胞的比值,即P/N比值.比值≥1,属于正常,比值＜1,则可能受试物对骨髓细胞产生毒性. 结果：Ni-Cr-Ti合金组、纯钛浸提液组每1 000个嗜多染红细胞的微核细胞数与阴性对照组比较,差异无显著性意义（P＞0.05）,即Ni-Cr-Ti合金、纯钛浸提液对骨髓细胞无毒性.阳性对照组每1 000个嗜多染红细胞的微核细胞数高于Ni-Cr-Ti合金组、纯钛浸提液组,差异有显著性意义（P＜0.01）,对骨髓有毒性作用.Ni-Cr-Ti合金组、纯钛浸提液组P/N比值均≥1. 结论：自制Ni-Cr-Ti合金对小鼠无致畸作用,有较良好的生物相容性.     

A chloroquine elution technique for platelet serology

The authors describe a prototype elution method employing chloroquine, a quinoline derivative, to elute IgG antibodies from the platelet surface. This chloroquine elution technique is relatively easy to perform and is effective in the removal of alloantibodies from the platelet surface. Eluted alloantibody was immunologically active once the chloroquine was removed from the eluate. The major advantage of this technique is that serologic testing of platelets after elution is possible, as 50 percent of the platelets remain after exposure to hypertonic acid chloroquine solution. Antigens on the platelet surface maintained their antigenicity subsequent to treatment, although measurable reductions in PIA1 reactivity occur. The elution technique was also successful in removing IgG from the platelet surface in patients with diseases involving elevated levels of platelet-associated IgG.     

Anti-Jka, -C, and -E in a single patient, initially demonstrable only by the manual hexadimethrine bromide (Polybrene) test, with incompatibilities confirmed by 51Cr-labeled red cell studies

Published reports have confirmed the superior sensitivity of the manual hexadimethrine bromide (Polybrene) test (MPT) for demonstrating many alloantibodies in vitro; however, the clinical significance of alloantibodies demonstrable exclusively by MPT has not been shown conclusively. A patient with macroglobulinemia experienced chills, fever, hemoglobinemia, and hemoglobinuria following the transfusion of 1 unit of red cells (RBCs) shown to be compatible by the low-ionic-strength antiglobulin (LIS-AG) method. Serologic investigation was negative. Intravascular hemolysis occurred with a second "compatible" unit. Serologic studies were again negative by LIS-AG and ficin-AG methods, but revealed anti-Jka by MPT. Both donors were Jk(a+b-), and 51Cr studies of the second donor's RBCs revealed a t1/2 of less than 30 minutes, with marked intravascular hemolysis. A LIS-AG-compatible Jk(a-) unit was transfused uneventfully, but with no rise in hematocrit. MPT next revealed anti-C; subsequent 51Cr studies with the Jk(a-), Cc donor's RBCs showed a 51Cr t1/2 of 100 minutes with slight intravascular lysis. Four transfusions of Jk(a-), C- blood were uneventful, but 5 days later the patient's hemoglobin declined. The following day, anti-E was demonstrable exclusively by MPT. 51Cr-labeled Jk(a-), C-, E- RBCs had normal 24-hour survival. The patient's hemoglobin rose to 11 g per dl following transfusions of Jk(a-), C-, E- RBCs, and he was discharged. In vitro studies employing the patient's purified IgM paraprotein revealed no interference with alloantibody binding or detection.     

盐酸维拉帕米渗透泵片溶出度与人体生物利用度研究

溶出度按Weibull's分布处理得T_d=5.76 h,T₅₀=3.9 h,零级溶出速度常数K_t=9.9450,平均体外溶解时间MDT=5.391 h。测定8名健康受试者,单剂量口服,得C_max=76.2±16.7 ng/ml,T_amx=8.0 h,t_1/2=9.75 h,MRT=19.41 h,MAT=5.34 h,与Knoll公司SR片相比,F_rel=101.71%;与市售普通片相比,F_rel=96.16%。多剂量口服,得C_max=121.47±34.5 ng/ml,T_max=7.14 h。按Loo-Riegelman方程处理表明体内外显著相关。理论值与实测值基本相符。     

沙尘天气大气颗粒物对学龄儿童最大呼气流速的影响

目的 研究沙尘天气颗粒物浓度与学龄儿童最大呼气流速(PEFR)之间的关系.探讨沙尘天气颗粒物对儿童肺功能的影响.方法 于2006年4月27日-6月5日连续40d对内蒙古包头市1所小学107名四年级小学生进行每日3次PEFR的测定,同时监测和收集每日大气PM2.5、PM1O、NO2和SO2浓度以及气温和相对湿度,通过问卷调查了解儿童年龄、性别、身高、体重、哮喘病史、慢性呼吸系统疾病家族史、被动吸烟等情况.应用线性混合效应模型,在控制了个体特征、气象因素的情况下估计PM2.5和PM10对儿童PEFR的影响.结果 单污染物模型和多污染物模型均显示,PM2.5和PM10的日均浓度与沙尘天气当日及之后3 d内儿童的PEFR日均值都存在明显的负相关(P<0.01),其中以滞后1 d的效应最强.在多污染物模型中调整了NO2和SO2的影响之后,PM2.5和PM10的日均浓度每增加10μg/m3,儿童PEFR在沙尘天气1 d之后的日均值就分别降低0.245和0.121 L/min,有统计学意义(P<0.01).结论 学龄儿童PEFR日均值下降与包头市沙尘天气颗粒物浓度的升高有关.