Intrinsic resistance to anticancer agents in the murine pancreatic adenocarcinoma PANC02

Summary PANC02 is a ductal adenocarcinoma of the pancreas that is resistant to every known class of clinically active antitumor agent. To study the mechanism(s) underlying the intrinsic drug resistance of this tumor, a mammary adenocarcinoma (CA-755) that also grows in C57/BL mice and is known to be drugsensitive was used for comparison. PANC02 resistance and CA-755 sensitivity to several antitumor agents and to X-ray therapy was confirmed in mice, and PANC02 also demonstrated relative resistance in tissue culture. Relative to Chinese hamster ovary (CHO) and CA-755 cells, PANC02 did not appear to show a higher rate of mutation to drug resistance in culture as based on the 6-thioguanine resistance marker. Although P-glycoprotein characteristic of the multidrug resistance (MDR) phenomenon could be demonstrated at the mRNA level using a sensitive RNAse protection assay, the level of expression found was several orders of magnitude lower than that observed in phenotypic MDR cell lines. Furthermore, quinidine failed to increase the sensitivity of PANC02 cells to Adriamycin under conditions that clearly potentiated the toxicity of the drug to a CHO cell line exhibiting classic MDR traits. The heterogeneity in the distribution of drugs was inferred as being significantly greater in PANC02 versus CA-755 cells in vivo as based on measurements of within-animal, within-tumor variance in the distribution of the marker compounds inulin and antipyrine. Although it may not be the only mechanism involved, this greater intratumor heterogeneity in drug distribution could theoretically play a major role in the intrinsic drug resistance of PANC02 in vivo.Supported by grant CH-458 from the American Cancer Society, by grant CA-28034 from the National Cancer Institute, and in part by Cancer Center Core Support grant, NIH-NCI-CA-16672. Animals were maintained in facilities approved by the American Association for Accreditation of Laboratory Animal Care and in accordance with current United States Department of Agriculture, Department of Health and Human Services, and National Institutes of Health regulations and standards     

Autoantibodies to Serum Proteins in Women with Recurrent Spontaneous Abortion: Subsequent Pregnancy Outcome

Sera from 130 first trimester pregnant women were tested for their serum antibody level against a naturally occurring serum antigen purified from non-pregnancy sera. IgG and IgM antibody level was measured using enzyme linked immunosorbant assay. Results indicate that patients with multiple abortion (n=26) have significantly (p=0.0029) lower level of IgG antibody and significantly (p=0.0001) higher level of IgM antibodies; against the serum antigen as compared to the patients with successful pregnancies with no history of miscarriage (n=63). Western blot analysis identified the scrum antigen recognized by the IgM antibody as a 24 kDa molecular mass component. These IgG and IgM antibodies may play an important role in the outcome of pregnancy.     

甲状腺病变患者血清Leptin的浓度变化

目的探讨甲状腺病变患者血清瘦素(leptin)浓度的变化及意义.方法本文用放射免疫分析(RIA)方法测定了114例甲状腺病变患者血清Leptin和总睾酮(TT)的浓度.结果统计学处理结果显示各病变组男性与正常对照组男性间,Leptin和TT的浓度差异均有显著性意义.结论血清Leptin的浓度变化可作为了解甲状腺病变患者营养状况的辅助指标.     

Kringle 5的真核植物细胞穿梭表达载体的构建

目的：构建含有目的基因kring5的真核植物细胞穿酸表达载体。方法：应用RT－PCR方法，从正常人肝脏组织中获得kringle5基因，测序后，再通过DNA重组技术，将kringle5基因片段克隆到真核植物细胞表达载体pBI121和pCAMBIA3301上。结果：得到的kringle5基因序列测定结果与文献相符，重组载体pB1k5和pC33k5经酶切鉴定正确，含有植物高效表达CaMV35S启动子。结论：重组载体pB1k5和pC33k5不仅可以在大肠杆菌中稳定复制，而且可以在植物细胞中表达。     

母血中胎儿有核红细胞的荧光原位杂交法在产前诊断中的可行性探讨

探讨荧光原位杂交法（FISH）对母血中胎儿有核红细胞（NRBC）进行无创性产前诊断的可行性。20例孕龄15-20周的孕妇外周血经不连续密度梯度离心、制片、显微镜下识别并共计数NRBC及定位，然后行Y染色体的FISH检测。结果发现10例孕男性胎儿的孕妇外周血细胞涂片中每例均有阳性杂交信号出现；阳性率为60％（24/40）。10例孕女性胎儿的孕妇外周血细胞涂片中1例出现阳性杂交信号；阴性率为95％（38/40），假阳性率仅为5％（2/40）。结果提示FISH法对于用母血中分离到的胎儿细胞进行染色体异常的无创性产前遗传学检查具有重要意义。     

INAUGURAL ARTICLE by a Recently Elected Academy Member:The cell surface metalloprotease/disintegrin Kuzbanian is required for axonal extension in Drosophila

It has long been suspected that proteolytic activity associated with advancing growth cones may be required for axon extension. We have isolated mutations in the kuzbanian (kuz) gene, which is expressed in the nervous system and encodes a putative zinc metalloprotease with a disintegrin domain. Drosophila embryos with loss-of-function mutations in kuz have dramatic defects in the development of central nervous system axon pathways, with many axons stalling and failing to extend through the nerve cord. This phenotype is rescued by panneural expression of kuz mRNA in the embryo. These results show that the Kuz metalloprotease is required for axon extension, suggesting a requirement for proteolytic activity at the growth cone surface.     

HLA‐DPB1 allelic frequency of the Pumi ethnic group in south‐west China and evolutionary relationship of Pumi with other populations

A sequencing‐based typing of the HLA‐DPB1 gene was carried out in 51 unrelated healthy individuals from the Yunnan Pumi ethnic minority. A total of 18 DPB1 alleles, in which DPB1*0501 (52.0%) and DPB1*0402 (15.7%) greatly predominated, were found, of which alleles DPB1*20011, 2201, 3601, 3701, 3801, 4901, 5001 and 8001 were recorded for the first time in the Chinese population. This may be because the typing methods used in previous genotyping of Chinese populations were of lower sensitivity than that used in our study. A dendrogram constructed by the maximum likelihood method showed that the Pumi ethnic minority belongs to the Asian/Australasian cluster and has the closest relationship to Trobriander, implying an unusual relationship between Australasian and South China populations. However, the Yi ethnic minority, which also comes from the ancient Qiang, did not show a very close relationship with the Pumi. This is probably because the Pumi were historically assimilated by local south‐west China populations.     

血脂代谢紊乱与冠状动脉病变严重程度的关系

目的:分析血脂代谢异常与冠状动脉狭窄程度的关系.方法:对366例因胸痛而就诊的患者行选择性冠状动脉造影,按冠状动脉狭窄程度分为正常对照组、单支病变组、双支病变组、多支病变组.同时观察患者血脂各成分,并对各组指标进行统计学分析.结果:总胆固醇(TC)、甘油三脂(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C),在各组之间存在差异,尤其多支病变组与正常组之间差异显著(P＜0.01).TC、TG、LDL-C随冠状动脉病变加重而增加,HDL-C随冠状动脉病变加重而减少,LDL-C与冠状动脉狭窄程度呈正相关,HDL-C与冠状动脉狭窄程度呈负相关.结论:血脂代谢紊乱与冠状动脉狭窄的发生发展有内在的联系,对于预测有无冠状动脉病变及其进展有一定临床意义.     

跟骨骨折的手术治疗

目的 探讨跟骨骨折手术治疗方法。方法 采用外侧切口，通过跟骨外侧骨皮质开门．将骨折复位后植骨．重建钢板螺钉内固定术．治疗24例（26足)。结果 术后均获5～32个月随访，按门振武等评分际准．优17例，良5例，差2例．结论 严重跟骨骨折手术治疗效果较满意。     

假体隆乳术后并发症的防治

目的探讨乳房假体隆乳术后并发症产生的相关因素及预防方法。方法对198例患者乳房假体隆乳术后1~17年出现的并发症进行分析,阐述防治措施,针对不同情况进行相应的处理。结果本组198例患者,其中92例患者随访半年至1年,除Ⅲ°包膜挛缩患者术后仍出现Ⅱ~Ⅲ°包膜挛缩外(包膜松解术后3例,包膜切除术后4例),余患者对治疗效果满意。结论乳房假体隆乳术后出现的并发症,多数是可以预防和治疗的,只要术中操作规范,对并发症及早准确的处理,是提高手术效果,减少并发症发生的有效方法。