血脂监测在防治Ⅱ型糖尿病患者继发动脉粥样硬化中的意义

目的探讨血脂代谢紊乱跟Ⅱ型糖尿病(ⅡDM)患者继发动脉粥样硬化并症的关系。方法采用奥林巴斯Au-640全自动生化分析仪,测定Ⅱ型糖尿病患者和健康对照组的空腹血糖(GLU)、胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、载脂蛋白Al(ApoAl)和载脂蛋白B100(ApoBloo),并进行统计、比较并与患者的病情进行对比分祈,并对高血糖、血脂组患者跟踪观察、治疗。结果Ⅱ型糖尿病组同健康对照组比较、Ⅱ型糖尿病患者中有合并症组跟无合并症组、高血糖组跟血糖正常组比较,CHO、TG和ApoBloo的含量均升高(P<0.05),而HDL-C和ApoAI含量降低(P<0.05)。而高血糖、血脂组患者,已经初步出现或在随后的观察中出现了动脉粥样硬化等相关的临床表征,且治疗效果不佳。结论Ⅱ型糖尿病患者血脂的异常,特别是CHO、TG的大幅升高,提示患者在出现动脉硬化性心血管合并症之前,体内已经具备了诱发合并症的生化基础,应早期采取针性治疗和预防措施。     

Plasminogen activator system modulates invasivecapacity and proliferation in prostatic tumor cells

The malignant phenotype of prostatic tumor cells correlates with the expression of both uPA and itscell-membrane receptor (uPAR); however, there is little information concerning the role of cell-bound uPAin matrix degradation and invasion. Our results suggest that cell-associated uPA plays a key role in regulat-ingthe amount of plasmin present at the surface of prostatic carcinoma (PRCA) cells and show that differ-entialproduction of uPA corresponds with the capacity to bind and activate plasminogen. In addition, weprovide direct evidence that both uPA secretion and the presence of uPA-uPAR complexes characterize theinvasive phenotype of PRCA cells and suggest the existence of several pathways by which tumor cells acquireplasmin activity. LNCaP cells (which do not produce uPA but express uPAR) may activate plasmin throughexogenous uPA. In vivo, the source of uPA may be infiltrating macrophages and/or fibroblasts as observedin several other systems. PAI-1 accumulation in the conditioned medium (CM) limits plasmin action to thepericellular microenvironment. Our results indicate that MMP-9 and MMP-2 are also activated by plasmingenerated by cell-bound but not by soluble, extracellular uPA. Plasmin activation and triggering of the pro-teolyticcascade involved in Matrigel invasion is blocked by antibodies against uPA (especially by anti- A-chainof uPA which interacts with uPAR) and by PA inhibitors such as p-aminobenzamidine which mayregulate levels of cell-bound uPA. uPA may also regulate growth in PRCA cells. Indeed, antibodies againstuPA A-chain (and also p-aminobenzamidine treatment) interfere with the ATF domain and inhibit cell growthin uPA-producing PC3 and DU145 prostate cancer cell lines, whereas exogenous uPA (HMW-uPA with ATF)induces growth of LNCaP prostate tumor cell line. These data support the hypothesis that in prostatic can-cerpatients at risk of progression, uPA/plasmin blockade may be of therapeutic value by blocking both growthof the primary tumor and dissemination of metastatic cells. ©Kluwer Academic Publishers     

Localization of a gene for otosclerosis to chromosome 15q25-q26

Among white adults otosclerosis is the single most common cause of hearing impairment. Although the genetics of this disease are controversial, the majority of studies indicate autosomal dominant inheritance with reduced penetrance. We studied a large multi- generational family in which otosclerosis has been inherited in an autosomal dominant pattern. Five of16 affected persons have surgically confirmed otosclerosis; the remaining nine have a conductive hearing loss but have not undergone corrective surgery. To locate the disease- causing gene we completed genetic linkage analysis using short tandem repeat polymorphisms (STRPs) distributed over the entire genome. Multipoint linkage analysis showed that only one genomic region, on chromosome 15q, generated a lod score >2.0. Additional STRPs were typed in this area, resulting in a lod score of 3.4. STRPs FES (centromeric) and D15S657 (telomeric) flank the 14. 5 cM region that contains an otosclerosis gene.      

L—门冬酰胺酶前体脂质体对小鼠毒性及对实验性肿瘤作用

目的：研究L－门冬酰胺酶（L－Asparaginase,L-A)前体脂质体（Proliposome,PL)[L-APL]iv对小鼠的毒性及对荷瘤小鼠的抗肿瘤活性。方法：以小鼠的急性毒性和外周血中白细胞数及血小板数为指标观察药物对小鼠的毒性及以荷瘤小鼠的瘤重和生命延和工率观察药物的抗肿瘤活性;结果：L－APL iV对小鼠的急性毒性与L－A相比明显降低,L－APL对正常小鼠外周血中白细胞数,血小板数无明显影响,而相同剂量L－A对小鼠外周血中白细胞数,血小板数明显降低。与对照组相比,L－APL和L－Aip可明显延长腹水型小鼠移瘤L1210,P388的存活天数,与同剂量L－A相比,L－APL高剂量有明显延长腹水型小鼠移植瘤的存活天数作用。L－APL及L－A ip对小鼠移植瘤Heps,EC实体型的肿瘤生长具有明显的抑制作用,两者抑瘤作用相近。结论：L－APL对小鼠的毒性明显小于相同剂量的L－A,L－APL不仅保持了L－A的抗肿瘤活性,而且有明显的增效作用。     

Postoperative adjuvant radiotherapy and 5-fluorouracil chemotherapy for rectal carcinoma

Postoperative combined modality therapy with radiotherapy and 5-fluorouracil (5FU) chemotherapy is an effective adjuvant approach that reduces locoregional and distant metastatic disease in patients with high-risk rectal carcinoma. However, this approach results in a treatment regimen of at least 6 months’duration. The present prospective study investigates the integration of radiotherapy and 5FU chemotherapy in a protocol designed to minimize toxicity and reduce the overall treatment time. A total of 40 patients with TNM stage II or III disease received postoperative radiotherapy at four fractions per week with weekly 5FU bolus injections delivered on the fifth non-radiotherapy day. Patients also received systemic chemotherapy with leucovorin both before and after pelvic irradiation, with the total treatment duration extending for only 18 weeks. Patients were able to complete radiotherapy in 90% of cases, while the delivery of full-dose chemotherapy was achievable in the vast majority. The incidence of haematologic and gastrointestinal toxicities requiring the cessation of treatment was acceptable. With a median follow-up of 20.9 months among surviving patients, the estimated progression-free and overall survival at 2 years were 71 % and 79%, respectively.     

Osteitis condensans ilii: prevalence and characteristics of a neglected mimic of sacroiliitis

Clinical Rheumatology - Osteitis condensans ilii (OCI) is a benign condition characterised by triangular sclerosis of the iliac bone which may mimic radiographic sacroiliitis. Prevalence is...     

Prostate cancer cell proliferation is strongly reduced by the epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 in vitro on human cell lines and primary cultures

PURPOSE: To investigate the effects of the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) ZD1839 ('Iressa') on the cellular proliferation of androgen-sensitive and androgen-independent human prostatic cancer cell lines and primary cultures in vitro. EXPERIMENTAL DESIGN: In this study, we investigated the effects of the quinazoline ZD1839, a potent, selective EGFR-TKI, on the EGFR autophosphorylation and cellular proliferation of androgen-sensitive (ND1, LNCaP, and ALVA-31) and androgen-independent (PC3, DU145, and TSU-Pr1) human prostatic cancer cell lines and 20 primary cultures derived from human prostatic cancer tissue. RESULTS: EGFR was present and phosphorylated in all cell lines tested. ZD1839 reduced EGFR autophosphorylation in intact cell lines with IC(50)s of 0.46-0.97 microM, and inhibited cellular proliferation with IC(50)s of 0.37-1.03 microM. Constitutive EGFR autophosphorylation was low in primary cell cultures, but addition of EGF (50 ng/ml) caused marked EGFR autophosphorylation; cellular proliferation in the presence of EGF was inhibited by ZD1839 with a mean IC(50) of 0.45 microM. At doses >1 microM, ZD1839 induced apoptosis in both androgen-dependent and androgen-independent PCa cell lines. CONCLUSION. Our experiments suggest that EGFR-TKIs such as ZD1839 may have potential in blocking the growth and progression of human prostatic cancers even in early phases of the disease.