Estrogen receptor-associated expression of keratinocyte growth factor and its possible role in the inhibition of apoptosis in human breast cancer

Although estrogen is known to play a crucial role in the pathogenesis of breast cancer, the molecular mechanisms underlying the action of estrogen remain elusive. In the present study, we focused on keratinocyte growth factor (KGF) and its receptor (KGFR) in the pathogenesis of breast cancer, as a growth factor mediating estrogen action, since significant roles of KGF were demonstrated in various steroid hormone-dependent tissues. First, using paraffin-embedded specimens from 42 breast cancer patients, we examined expression patterns of KGF and KGFR by both immunohistochemistry using newly generated antibodies and nonradioactive in situ hybridization with T-T dimerized synthetic oligonucleotide probes. We next compared the results with the expression of estrogen receptor (ER) alpha and beta, proliferative activity and apoptotic frequency (TUNEL staining). Also, the similar approaches were taken to analyze the expression and role of KGF in ER-positive (MCF7, ZR-75-1) and ER-negative (SK-BR-3, MDA-MB-231) human breast cancer cell lines in vitro. In the surgical specimens, KGF was expressed in cancer cells as well as stromal cells in 19/42 cases (45%), while KGFR was found in cancer cells in 24/42 cases (57%). The distribution of protein and mRNA in the analysis of both KGF and KGFR expression generally coincided. Moreover, KGF expression was closely associated with the expression of ER alpha, and the coexpression of KGF and KGFR significantly correlated with lower TUNEL index, but not with proliferative activity. In accordance with the in vivo findings, KGF expression was detected only in ER alpha-positive MCF7 and ZR-75-1 cells in vitro. And more importantly, we found the inhibitory effect of KGF upon the induction of apoptosis by anticancer drugs in MCF7 cells. Collectively, our results indicate that ER alpha may be involved in KGF expression, and that KGF may play antiapoptotic roles, rather than mitogenic, in human breast cancer.     

Early rehabilitation program in postmastectomy patients: a prospective clinical trial

The purpose of this study was to determine whether 20 patients who received an early postmastectomy rehabilitation treatment program showed more improvement in range of shoulder motion and functional activities than 13 patients who received instruction for exercise only. Data were obtained at preoperatively, three days after operation, at discharge and at postdischarge one month for each patient on parameters such as range of motion of the ipsilateral shoulder joint, upper extremity circumferential measurements, as well as 10 elements of shoulder function. Postoperatively, both groups showed an increased range of motion of the shoulder joint and improved functional activities, but the group that received postoperative rehabilitation management had a better range of shoulder motion and less difficulty in five items for functional assessment. This study also showed that an early rehabilitation program did not increase postoperative complications. We concluded that an early rehabilitation program or intensive instruction program only by a well-trained physical therapist or physiatrist was beneficial to postmastectomy patients in regaining the function and range of shoulder motion, and significantly better in a rehabilitation group.     

骨髓基质细胞促进永久性局灶性脑缺血大鼠脑室下区的神经发生

目的 探讨移植骨髓基质细胞(BMSCs)对永久性局灶性脑缺血大鼠脑室下区(SVZ)细胞增殖的影响及其增殖细胞类型分析. 方法制作永久性局灶性脑缺血大鼠模型,分为空白对照组(MCAO)、PBS对照组(MCAO PBS)和治疗组(MCAO BMSCs),每组动物再分为脑缺血后7d和14d亚组.空白对照组不予处理,PBS对照组在脑缺血后1d移植PBS,治疗组在脑缺血后1d移植BMSCs.用Zausinger六分法检测神经功能恢复情况;注射5-溴脱氧鸟嘧啶核苷(BrdU)标记SVZ的新增殖细胞,免疫荧光双重标记检测新增殖细胞的类型. 结果在脑缺血后7d和14d,与两个对照组相比,治疗组的神经功能评分较高,有显著性差异(P<0.05);脑缺血后14d,治疗组的大鼠患侧SVZ的BrdU阳性细胞较其余两组高,存在显著差异(P<0.05);免疫荧光双重标记显示,新增殖细胞表达神经元和星形胶质细胞的标志物,提示新增殖细胞为神经元和神经胶质细胞的混合体. 结论 BMSCs可以改善永久性局灶性脑缺血大鼠的神经功能,其机制可能与促进SVZ的神经细胞增殖有关.     

全膝关节置换术的康复治疗及护理

目的 探讨人工全膝关节置换术后的康复训练方法。方法 回顾分析2001年8月至2005年8月16例（17膝）人工全膝关节置换术后病人康复训练的过程及效果。结果 人工全膝关节置换术后经过系统康复训练，所有膝关节功能评分达到（70-86分）平均80分。结论 人工全膝关节置换手术效果与术后全面系统的康复训练密切相关。     

Gain-of-function polymorphism in mouse and human Ltk: implications for the pathogenesis of systemic lupus erythematosus

Systemic lupus erythematosus (SLE), a complex multigenic disease, is a typical antibody-mediated autoimmune disease characterized by production of autoantibodies against a variety of autoantigens and immune complex-type tissue inflammation, most prominently in the kidney. Evidence suggests that genetic factors predisposing to aberrant proliferation/maturation of self-reactive B cells initiate and propagate the disease. In SLE-prone New Zealand Black (NZB) mice and their F1 cross with New Zealand White (NZW) mice, B cell abnormalities can be ascribed mainly to self-reactive CD5+ B1 cells. Our genome-wide scans to search for susceptibility genes for aberrant activation of B1 cells in these mice showed evidence that the gene, Ltk, encoding leukocyte tyrosine kinase (LTK), is a possible candidate. LTK is a receptor-type protein tyrosine kinase, belonging to the insulin receptor superfamily, and is mainly expressed in B lymphocyte precursors and neuronal tissues. Sequence and functional analyses of the gene revealed that NZB has a gain-of-function polymorphism in the LTK kinase domain near YXXM, a binding motif of the p85 subunit of phosphatidylinositol 3-kinase (PI3K). SLE patients also had this type of Ltk polymorphism with a significantly higher frequency compared with the healthy controls. Our findings suggest that these polymorphic LTKs cause up-regulation of the PI3K pathway and possibly form one genetic component of susceptibility to abnormal proliferation of self-reactive B cells in SLE.     

PCR-RFLP based molecular typing of enteroviruses isolated from patients with aseptic meningitis in Korea

Summary.  We have evaluated PCR–RFLP as a practical method for rapid typing of enteroviruses causing aseptic meningitis in Korea. Through blind examination of 80 clinical isolates from patients with aseptic meningitis, we have compared the results of conventional serotyping with PCR–RFLP based genotyping, which was developed for this study. Among the 80 case isolates, which had been previously typed by routine neutralization test, only 42 cases (52.5%) were matched with typing by PCR–RFLP. The result clearly demonstrated that the enterovirus serotype does not coincide with the genotype. Therefore, the classification of enteroviruses by genotyping with PCR–RFLP, although rapid and simple, may be complicated by regional or seasonal differences. However, the PCR–RFLP method developed in this study is applicable to the epidemiological study of enteroviruses when regional or seasonal differences exist, and is useful in identifying the source of an infection. Received August 6, 2001; accepted April 15, 2002 Published online July 10, 2002     

兔激素性股骨头坏死的血液流变学改变

目的　探讨血液流变学指标在激素性股骨头坏死过程中的变化规律及其作用。方法　20只兔随机分成2组，每组10只。A组（激素性股骨头坏死动物模型组）：间隔24h耳缘静脉内2次注射大肠杆菌内毒素，每次40μg/kg，注射内毒素后注射醋酸泼尼松龙20mg/kg。B组（正常对照组）。两组分别在注射后24h、72h、7d、14d 及21d，进行血浆黏度、全血黏度、血小板计数及血脂测定，21d取股骨头和肝脏行病理组织学观察。结果　A组用药后24h血浆黏度、全血黏度升高，血脂升高(P<0.01)血小板计数减少(P<0.01)，用药后72h、7d、14d 及21d，持续异常，与B组相比差异显著。A组21d时病理切片见股骨头骨细胞和肝细胞变性、坏死。结论　在激素性股骨头坏死动物模型中，血液流变学指标异常在引起血栓前状态，形成血栓导致骨坏死过程中可能发挥了重要作用。     

High-performance liquid chromatographic determination of trimebutine and its major metabolite, N-monodesmethyl trimebutine, in rat and human plasma

A rapid, selective and very sensitive ion-pairing reversed-phase HPLC method was developed for the simultaneous determination of trimebutine (TMB) and its major metabolite, N-monodesmethyltrimebutine (NDTMB), in rat and human plasma. Heptanesulfonate was employed as the ion-pairing agent and verapamil was used as the internal standard. The method involved the extraction with a n-hexane-isopropylalcohol (IPA) mixture (99:1, v/v) followed by back-extraction into 0.1 M hydrochloric acid and evaporation to dryness. HPLC analysis was carried out using a 4-microm particle size, C18-bonded silica column and water-sodium acetate-heptanesulfonate-acetonitrile as the mobile phase and UV detection at 267 nm. The chromatograms showed good resolution and sensitivity and no interference of plasma. The mean recoveries for human plasma were 95.4+/-3.1% for TMB and 89.4+/-4.1% for NDTMB. The detection limits of TMB and its metabolite, NDTMB, in human plasma were 1 and 5 ng/ml, respectively. The calibration curves were linear over the concentration range 10-5000 ng/ml for TMB and 25-25000 ng/ml for NDTMB with correlation coefficients greater than 0.999 and with within-day or between-day coefficients of variation not exceeding 9.4%. This assay procedure was applied to the study of metabolite pharmacokinetics of TMB in rat and the human.     

抗慢性B淋巴细胞白血病患者IgM单抗相对亲和力的分析

本文采用间接ELISA法检测了11株抗B-CLL患者IgM腹水和杂交瘤上清McAb的相对亲和力。结果提示,各株McAb结合抗原的相对亲和力不同。根据50％最大结合浓度分为两组。其中4株杂交瘤上清McAb与纯化腹水McAb测得结果基本吻合。实验结果为合理地选用这些单抗提供了重要依据。     

初三学生成就动机与学业成绩的关系研究

编制中学生成就动机量表 ,考察 2 86名初三学生的成就动机状况。运用逐步回归分析探讨成就目标、归因方式、自我效能与学业成绩的关系 ,并对成就目标进行自我效能和归因方式的回归分析。结果表明 :影响初三学生学业成绩的主要成就动机因素是自我效能、表现目标、能力归因和掌握目标 ,努力归因、运气归因和自我效能是影响初三学生成就目标的主要因素 ,客观因素归因也会影响表现目标。对研究结果进行本土化思考 ,建构中学生成就动机的理想模型