The p53 positive Bcl-2 negative phenotype is an independent marker of prognosis in breast cancer

The purpose of this work was to determine if the immunohistochemical p53 (+) Bcl-2 (-) phenotype predicts survival in breast cancer patients. Tissue from 819 cases of resected primary breast cancer, presented between 1986 and 1998, were assembled in tissue microarray format. Clinicopathological data and prospective disease specific survival data were collected prospectively and immunohistochemical analyses of p53 and Bcl-2 expression were performed using antibodies DO-7 (p53) and 124 (Bcl-2) employing a standard IHC protocol. The expression data were correlated with clinicopathological variables and outcomes in both univariate (chi(2)) and multivariate (Cox's regression) analyses. Abnormal p53 expression and positive Bcl-2 expression were detected in 29% (193/673) and 46% (307/673) of tumours, respectively. On univariate analysis Bcl-2 expression was correlated with the clinicopathological features of less aggressive disease and loss of Bcl-2 expression correlated with a reduction in survival (log rank = 11.91; p < 0.001). p53 expression correlated with the clinicopathological features of aggressive cancers and a reduction in survival (log rank = 17.81; p < 0.001). Nineteen percent (127/673) of tumours displayed a p53 (+) Bcl-2 (-) phenotype. Kaplan-Meier analysis revealed a significant reduction in survival in these cases (log rank 34.01; p < 0.001). Multivariate analysis showed that while neither p53 expression nor Bcl-2 expression alone had independent prognostic significance, the p53 (+) Bcl-2 (-) phenotype remained independently associated with a worse prognosis (HR 1.79 95%CI 1.10-2.89 p = 0.018).     

Factors predicting differences among general practitioners in test ordering behaviour and in the response to feedback on test requests

BACKGROUND: In a population of 85 general practitioners diagnostic testordering behaviour has been changed by means of repeated individualfeedback provided since 1985. OBJECTIVES: We studied practitioner and practice characteristics which mayexplain differences in test ordering behaviour and in the extentto which general practitioners tend to change their behaviouraccording to the feedback. METHOD: In order to trace such variables, 75 general practitioners wereinterviewed. In our study request data from individual generalpractitioners were related to data from several questionnaires. RESULTS: We found no practice characteristics which were of influenceon the number of test requests by the general practitioner.Explanatory practitioner characteristics for this were foundto be years of experience and working hours per week in practice. CONCLUSIONS: More years of experience as a general practitioner and a shorterduration of consultations correlated with a better responseto advice given in the feedback. Keywords. Feedback, test ordering behaviour, practice characteristics, practitioner characteristics.     

拉氧头孢钠的极谱行为及其痕量测定方法

在HCI-KCI（ｐＨ1～2）介质中，用循环伏安和示差脉冲极谱（ＤＰＰ）等电化学方法研究了拉氧头孢钠（噻吗灵）的电极反应机理，并建立了用ＤＰＰ测定的新方法。其峰电位为-0.62V（ｖｓＡｇ/ＡｇＣｌ），峰电流与拉氧头孢钠浓度在1×10^-8～5×10^-6ｍｏｌ·Ｌ^-1（富集时间t_ac＝９０ｓ），5×10^-6～5×10^-5ｍｏｌ·Ｌ^-1（t_ac＝７０ｓ），5×10^-5～８×１０^-4ｍｏｌ·Ｌ^-1（t_ac＝30ｓ）范围内成线性关系。检测限为４×１０^-9ｍｏｌ·Ｌ^-1（t_ac＝９０ｓ）。本法可用于注射剂中该物质的测定，同时也探讨了直接测定尿中拉氧头孢钠的可能性。     

含氯石灰硼酸溶液的稳定性考察

目的：考究考察含氯石灰硼酸溶液的稳定性。方法：将含氯石灰按标示量的１２０％投料,使成品有效氯含量不低于标示量的１１０％。２５℃恒温下观察其含量变化。结果：含氯石灰和硼酸两溶液分别配制,贮藏３个月时有效氯含量不低于标示量的１００％,再混合后贮藏１个月时不低于８０％,即０．２５％ｃｌ。结论：两溶液可分别贮藏３个月,混合后可再贮藏１个月。     

伊贝母中伊贝碱甙C的分离和结构鉴定

自吉林栽培的伊贝母(Fritillaria pallidiflora Schrenk)中分得一种新的甾体生物碱甙,命名为伊贝碱甙C(yibeinosideC)。根据红外、质谱、氢谱、碳谱、¹H-¹HCOSY和¹H-¹³CCOSY谱确定其结构为22,26-环亚胺胆甾-6-酮-3-O-β-D-吡喃葡萄糖-(1→4)-β-D-吡喃半乳糖甙(1)。     

Flow cytometric screening of monoclonal antibodies for drug or toxin targeting to human cancer

Monoclonal antibodies (MAbs) that are candidates for antibody-directed therapy were evaluated by a flow cytometric method. This method accurately quantitates the intensity of staining and the percentage of cells from freshly derived primary tumors expressing the relevant cell surface antigens. This method was applied to human colorectal, gastric, and ovarian carcinomas. It allowed calculations of the number of drug molecules that potentially could be delivered by each MAb as well as selection of the optimal combinations of antibodies for treatment of each type of cancer. The binding of all the MAbs varied among the tumors, although combinations of antibodies reduced this problem. A combination of MAbs C14 and NCRC-23 recognized 97% of colorectal tumors. A combination of C14, NCRC-23, and 791T/36 recognized 95% of gastric tumors. Combinations of either 791T/36 and C14 or 791T/36 and NCRC-11 recognized 80% of ovarian tumors. The number of cells binding with a single MAb varied within the tumor. The optimal anti-colorectal tumor antibody was NCRC-23 (anti-carcinoembryonic antigen), which recognized a mean of 65% of the large cells within a tumor at a mean antigen density of 4.9 X 10(5) sites/cell. The optimal anti-gastric tumor antibody was C14 (anti-Y hapten), which recognized a mean of 66% of the large cells within a tumor at a mean antigen density of 4.4 X 10(5) sites/cell. The optimal anti-ovarian antibody was 115/D8, which recognized 54% of the large cells at a mean antigen density of 4.2 X 10(5) sites/cell. These antigen densities were similar to those calculated for HLA/ABC antigens in colorectal and ovarian cancers. However, the gastric tumors expressed elevated levels of major histocompatibility complex class I antigens, with a mean density of 7.3 X 10(5) sites/cell. Combinations of antibodies that recognize a high proportion of tumor cells are likely to be necessary for MAb-drug targeting to prevent tumor recurrence and/or metastases.     

The influence of syngeneic anti-idiotypic antibody on the biodistribution of an anti-tumour monoclonal antibody in BALB/c mice

BALB/c mice were immunized against syngeneic murine 791T/36 monoclonal antibody (MAb) by intraperitoneal (i.p.) injection of the antibody conjugated to ricin toxin A chain. Subsequently, in these and control mice, the biodistribution of radioiodinated 791T/36 antibody and isotype-matched (IgG2b) control immunoglobulin was examined. Pre-treated mice showed marked perturbation of biodistribution of the 791T/36 antibody but not of control IgG2b. This was manifest as rapid hepatic clearance of the antibody which was followed by accelerated catabolism and excretion of the radiolabel. Anti-idiotypic antibodies were identified in immunotoxin pretreated mice by their ability to inhibit the binding of FITC-labelled 791T/36 antibody to tumour target cells. These studies show that antibody responses, even to only the idiotype of a MAb, may produce marked perturbation of its biodistribution. This has implications for the clinical use of human or chimeric MAbs for tumour imaging or targeting of therapeutic agents since, if anti-idiotypic antibodies are evoked, they could still prevent tumour localization of antibody or conjugate.     

环磷酰胺条件性免疫抑制反应动物模型的建立及有关机制的分析

环磷酰胺条件性免疫抑制反应动物模型的建立及有关机制的分析李乐群，汪静雪，宋德懋，范少光，梅林（北京医科大学生理学系，北京１０００８３）在神经免疫调节的研究中，近年来有报道证明某一无关刺激当与一些能够引起机体免疫反应的刺激（又称非条件刺激）相结合（强化...     

2－［对－（二甲氨基）苯乙烯］氯化甲基吡啶对大鼠心电图、豚鼠左心房收缩及乳头肌动作电位的影响

２－［对－（二甲氨基）苯乙烯］氯化甲基吡啶（ＤＳＰＭ－ＣＩ），是由氯取代２－［对－（二甲氨基）苯乙烯］碘化甲基吡啶（ＤＳＰＭ）上的碘而得。本文应用心电图、机械收缩描记方法及细胞内标准微电极技术，研究ＤＳＰＭ－Ｃｌ对大鼠心电图（ＥＣＧ）、豚鼠心房肌量效曲线及对豚鼠乳头肌快反应动作电位（ＡＰ）、高钾除极慢反应动作电位（ＳＡＰ）的影响。结果显示，ＤＳＰＭ－Ｃｌ（２ｍｇ·ｋｇ￣（－１））对大鼠有明显的负性频率、负性传导作用，分别使ＰＰ间期、ＰＲ间期延长达６６．２％（Ｐ＜０．０１），１７．０％（Ｐ＜０．０１），５０μｍｏｌ·Ｌ￣（－１）能明显抑制左心房收缩力，非竟争性拮抗Ｉｓｏ及ＣａＣｌ＿２对豚鼠左心房的正性肌力作用，ＰＤ￣２＇分别为４．６，４，３４，１００μｍｏｌ·Ｌ￣（－１）ＤＳＰＭ－Ｃｌ延长动作电位时程ＡＰＤ＿（９０），有效不应期（ＥＲＰ），降低高钾除极豚鼠乳头肌０期最大上升速率Ｖｍａｘ，其作用与Ｖｅｒ相似，提示ＤＳＰＭ－Ｃｌ可能为钙拮抗剂。     

A prospective study of NAT2 acetylation genotype, cigarette smoking, and risk of breast cancer

Polymorphisms in the N-acetyltransferase 2 (NAT2) gene are determinants of the rate of metabolic activation of carcinogenic compounds such as aryl aromatic amines. Homozygosity for any combination of three variant alleles in Caucasians defines 'slow' acetylators; presence of one or two wild-type alleles characterizes 'rapid' acetylators. Although most previous studies have not observed an overall elevation in risk of breast cancer among slow acetylators, a recent study observed that cigarette smoking was associated with a large increase in risk of breast cancer among slow acetylators. We assessed the relation between NAT2 acetylation status and breast cancer risk, and its interaction with smoking, in a prospective study of mainly Caucasian US women. Four hundred and sixty-six incident cases who were diagnosed with breast cancer after giving a blood specimen in 1989-90 were matched to 466 controls in a nested case-control study. NAT2 genotype was determined using PCR-RFLP assays. The multivariate relative risk (RR) comparing slow with rapid acetylators was 0.9 (95% CI 0.7-1.2). Among slow acetylators, current smoking immediately prior to diagnosis was not associated with a significant elevation in risk compared with never smoking rapid acetylators (RR = 1.4, 95% CI 0.7-2.6). No significant association was seen between pack-years of smoking and risk of breast cancer among either slow or fast acetylators. A non-significant elevation in risk was observed among women who smoked for > or = 5 years prior to first pregnancy and were rapid acetylators, compared with never smoking rapid acetylators (RR = 1.5, 95% CI 0.9-2.6). In analyses limited to 706 post-menopausal women, the elevated risks for current smokers immediately prior to diagnosis who were slow acetylators compared with never smokers who were fast acetylators were slightly stronger but still not statistically significant. In summary, we observed little evidence of an association between NAT2 genotype and breast cancer. In this prospective study, cigarette smoking was not appreciably associated with breast cancer among either slow or fast NAT2 acetylators.