Liver transplantation in Taiwan: the Chang Gung experience

Between March 1984 and February 1991, six orthotopic liver transplantations were performed at the Chang Gung Memorial Hospital in Taiwan. The indications for transplantation were Wilson's disease (5 patients) and biliary atresia (1 patient). Donors and recipients were matched only for size and ABO blood group compatibility, and the recipient operations were performed without the use of a venovenous bypass. Arterial reconstruction was carried out by end-to-end hepatic artery anastomosis (4), thoracic aortic conduit (1), or interposition of an iliac artery graft (1), whereas biliary reconstruction was accomplished by a choledochocholedochostomy using a T-tube stent (4) or a choledochocholedochostomy using an external cholecystostomy without stenting (2). Biliary complications occurred in three patients, and all required additional surgery. The average duration of donor-liver cold ischemia, operating time, and blood loss during surgery were 7 h and 50 min (range, 4.5–9 h), 13.5 h (range, 11.8–17h), and 4,385 ml (range, 750–12,000 ml) respectively. The immunosuppressive regimens included a cyclosporinsteroid combination (n=2) and a triple-drug combination (n=4). All except one of the surviving patients experienced at least one rejection episode that was reversed by a methyl-prednisolone bolus and/or recycle. One patient developed a primary cytomegalovirus (CMV) infection that responded well to Ganciclovir treatment. Two of the patients died, one of injuries sustained in a traffic accident 3 years after transplantation, and the other of massive upper gastrointestinal bleeding. The overall survival value at 3 months was 83%, and the follow-up period ranged from 3 months to 7 years. All of the survivors have achieved complete rehabilitation and currently enjoy an excellent quality of life with normal liver function. Althought the present study involved a small number of cases, our results indicate that liver transplantation can be successfully achieved in a high proportion of patients with acceptable morbidity, mortality, and cost in an Asian setting. The extreme shortage of donor organs is currently the most important obstacle limiting the application of liver transplantation in Taiwan.Presented at The Second International Symposium on Treatment of Liver Cancer. Taipei, 3–4 February 1991     

Characterization of prorenin activation using a synthetic peptide substrate.

Human renin is synthesized as an inactive zymogen (prorenin) which is processed to the active form. We synthesized an 11-amino acid peptide which spans the human prorenin processing site in order to develop a simple assay to study human prorenin activation. Six enzymes which are capable of activating recombinant prorenin in vitro were studied. Four of these enzymes digested the synthetic peptide in a specific fashion, as analyzed by reverse-phase high-performance liquid chromatography. Amino acid analysis of the purified digestion products revealed that trypsin cleaves between Arg-Leu, the authentic processing site, while kallikrein, plasmin and elastase all cleaved at alternate sites. On the other hand, pepsin and cathepsin D did not cleave this substrate, suggesting that the activation of prorenin by these proteases might occur at a site distinct from the authentic processing site. Our data suggest that this synthetic peptide may be used as a simple and specific assay for prorenin activation.     

Studies on the relationship between transaldolase activity and testosterone synthesis in Leydig cells of pubertalmice

Objective: To study the relationship between transaldolase activity, protein expression and testosterone synthesis in Leydig cells of pubertal mice. Methods: Leydig cells were cultured for 2 hours and 8 hours, to the Stimulation Group, hCG was added and to the Controls, only the vehicle. The testosterone concentration was then determined by enzyme-linked immunoadsordent assay (ELISA) and the transaldolase activity and protein expression by Western blot. Results: (1) Both the testosterone concentration and the transaldolase activity in both Stimulation Groups were significantly higher than those in the corresponding Controls (2 h: p<0.05-0.01; 8 h: P<0.001); (2) The ratios of the A isoform, the B isoform and the total transaldolase protein to β-actin between the Stimulation and Control Groups did not differ signifi-cantly. Conclusion: hCG stimulates the transaldolase activity as well as the testosterone synthesis in the Leydig cells of pubertal mice, indicating a positive relationship between them.     

C型臂X线机引导下经皮双侧骶髂拉力螺钉固定治疗骶骨H形骨折

目的探讨骶骨H形骨折可行的治疗方法。方法运用C型臂X线机引导下经皮双侧骶髂拉力螺钉固定治疗骶骨H形骨折15例。结果15例患者均获随访，随访时间7—34个月，骨折临床愈合时间3～5个月，术后均未留下明显行走障碍，下蹲等活动接近正常。结论在C型臂X线机精确引导下，经皮双侧骶髂拉力螺钉固定技术能有效地固定骶骨H形骨折中的垂直骨折，纠正骨盆垂直方向移位，操作简洁安全，疗效可靠。     

脊髓运动诱发电位在脊髓肿瘤手术中的监测应用

目的探讨脊髓运动诱发电位(SCMEP)在脊髓肿瘤手术中监测的应用价值.方法采用硬膜外电极在椎管内直接刺激脊髓记录脊髓运动诱发电位(SCMEP)监测脊髓肿瘤手术,并对17例肿瘤患者的手术监测的记录结果进行回顾性分析.结果SCMEP由于病变部位及性质、刺激电极与记录电极间的距离不同,波幅及潜伏期的差异较大,电极安放后与手术结束时的结果个体对照,相差不显著(P=0.083;P=0.387).7例术中波幅降低超过预警值20%,5例经短暂休息或改变手术方向后,波幅恢复正常.结论SCMEP的波幅变化是提示脊髓损伤的可靠性灵敏指标,对辅助医生进行手术安全操作,缩短手术时间,提高手术质量,减少术后神经功能障碍起到重要作用.     

人野生型parkin基因真核表达载体的构建及其在PC12细胞中的表达

目的 克隆人野生型parkin基因并构建真核表达载体pCDNA3．1—parkin，将重组质粒转染PC12细胞获得高表达人野生型parkin基因的PC12细胞克隆。方法 从胎脑组织中提取总RNA，用RT—PCR方法获得人野生型parkin基因的全长cDNA，插入pCR2．1—TA克隆载体中进行序列测定，测序正确后将其亚克隆至表达载体pCD—NA3．1，利用脂质体将重组质粒转染PC12细胞，经G418筛选获得抗性细胞克隆，采用RT—PCR和Western Blot方法鉴定人野生型parkin基因在PC12细胞中的过表达。结果 经限制性内切酶酶切图谱分析和DNA序列测定证实目的基因已插入重组质粒，RT—PCR和Western Blot证明经G418筛选得到的转基因PC12细胞克隆中存在人野生型parkin基因的表达。结论 成功构建了人野生型parkin基因的真核表达载体，获得了稳定表达人野生型parkin基因的PC12细胞克隆，为进一步研究parkin的生物学功能以及parkin在帕金森病发病机制中的作用奠定了良好的基础。     

颞下锁孔入路的显微解剖与临床应用

目的进行颞下锁孔入路解剖学研究,探讨其临床应用价值.方法取甲醛固定的成人尸头标本15例(30侧),采用神经内镜辅助的显微外科技术进行颞下锁孔手术解剖学研究.并采用该入路手术切除8例颅内肿瘤.结果颞下锁孔入路可以充分暴露鞍上区、脚间窝、岩斜区及脑干腹外侧区的神经、血管结构;岩骨尖最大磨除面积为306mm2.肿瘤全切除7例(87.5%).结论经颞下锁孔入路能很好地处理鞍上、岩斜区、脚间窝以及脑干腹外侧区的病变.     

Genome-wide scan identified QTLs underlying femoral neck cross-sectional geometry that are novel studied risk factors of osteoporosis.

A genome-wide screen was conducted using a large white sample to identify QTLs for FNCS geometry. We found significant linkage of FNCS parameters to 20q12 and Xq25, plus significant epistatic interactions and sex-specific QTLs influencing FNCS geometry variation. INTRODUCTION: Bone geometry, a highly heritable trait, is a critical component of bone strength that significantly determines osteoporotic fracture risk. Specifically, femoral neck cross-sectional (FNCS) geometry is significantly associated with hip fracture risk as well as genetic factors. However, genetic research in this respect is still in its infancy. MATERIALS AND METHODS: To identify the underlying genomic regions influencing FNCS variables, we performed a remarkably large-scale whole genome linkage scan involving 3998 individuals from 434 pedigrees for four FNCS geometry parameters, namely buckling ratio (BR), cross-sectional area (CSA), cortical thickness (CT), and section modulus (Z). The major statistical approach adopted is the variance component method implemented in SOLAR. RESULTS: Significant linkage evidence (threshold LOD = 3.72 after correction for tests of multiple phenotypes) was found in the regions of 20q12 and Xq25 for CT (LOD = 4.28 and 3.90, respectively). We also identified eight suggestive linkage signals (threshold LOD = 2.31 after correction for multiple tests) for the respective geometry traits. The above findings were supported by principal component linkage analysis. Of them, 20q12 was of particular interest because it was linked to multiple FNCS geometry traits and significantly interacted with five other genomic loci to influence CSA variation. The effects of 20q12 on FNCS geometry were present in both male and female subgroups. Subgroup analysis also revealed the presence of sex-specific quantitative trait loci (QTLs) for FNCS traits in the regions such as 2p14, 3q26, 7q21 and 15q21. CONCLUSIONS: Our findings laid a foundation for further replication and fine-mapping studies as well as for positional and functional candidate gene studies, aiming at eventually finding the causal genetic variants and hidden mechanisms concerning FNCS geometry variation and the associated hip fractures.     

Interleukin-1 and cancer progression: the emerging role of interleukin-1 receptor antagonist as a novel therapeutic agent in cancer treatment

The tumor microenvironment consists of tumor, immune, stromal, and inflammatory cells which produce cytokines, growth factors, and adhesion molecules that promote tumor progression and metastasis. Of particular interest in this setting is interleukin-1 (IL-1), a pleiotropic cytokine with numerous roles in both physiological and pathological states. It is known to be up regulated in many tumor types and has been implicated as a factor in tumor progression via the expression of metastatic and angiogenic genes and growth factors. A number of studies have reported that high IL-1 concentrations within the tumor microenvironment are associated with a more virulent tumor phenotype. Solid tumors in which IL-1 has been shown to be up regulated include breast, colon, lung, head and neck cancers, and melanomas, and patients with IL-1 producing tumors have generally bad prognoses. The exact mechanisms by which IL-1 promotes tumor growth remain unclear, though the protein is believed to act via induction of pro-metastatic genes such as matrix metalloproteinases and through the stimulation of adjacent cells to produce angiogenic proteins and growth factors such as VEGF, IL-8, IL-6, TNFα, and TGFβ. The IL-1 receptor antagonist (IL-1ra) is a naturally occurring inhibitor to IL-1 and acts by binding to the IL-1 receptor without activating it. The protein has been shown to decrease tumor growth, angiogenesis, and metastases in murine xenograft models. Our focus in this review is to summarize the known data on the role of IL-1 in tumor progression and metastasis and the use of IL-1 inhibition as a novel therapeutic approach in the treatment of solid organ malignancies.