Therapy-related myeloid neoplasms - what have we learned so far?

Therapy-related myeloid neoplasms are neoplastic processes arising as a result of chemotherapy, radiation therapy, or a combination of these modalities given for a primary condition. The disease biology varies based on the etiology and treatment modalities patients receive for their primary condition. Topoisomerase Ⅱ inhibitor therapy results in balanced translocations. Alkylating agents, characteristically, give rise to more complex karyotypes and mutations in p53. Other etiologies include radiation therapy, high-dose chemotherapy with autologous stem cell transplantation and telomere dysfunction. Poor-risk cytogenetic abnormalities are more prevalent than they are in de novo leukemias and the prognosis of these patients is uniformly dismal. Outcome varies according to cytogenetic risk group. Treatment recommendations should be based on performance status and karyotype. An in-depth understanding of risk factors that lead to the development of therapyrelated myeloid neoplasms would help developing riskadapted treatment protocols and monitoring patients after treatment for the primary condition, translating into reduced incidence, early detection and timely treatment.     

Proteomic analysis of pancreas derived from adult cloned pig

The potential medical applications of animal cloning include xenotransplantation, but the complex molecular cascades that control porcine organ development are not fully understood. Still, it has become apparent that organs derived from cloned pigs may be suitable for transplantation into humans. In this study, we examined the pancreas of an adult cloned pig developed through somatic cell nuclear transfer (SCNT) using two-dimensional electrophoresis (2-DE) and Western blotting. Proteomic analysis revealed 69 differentially regulated proteins, including such apoptosis-related species as annexins, lamins, and heat shock proteins, which were unanimously upregulated in the SCNT sample. Among the downregulated proteins in SCNT pancreas were peroxiredoxins and catalase. Western blot results indicate that several antioxidant enzymes and the anti-apoptotic protein were downregulated in SCNT pancreas, whereas several caspases were upregulated. Together, these data suggest that the accumulation of reactive oxygen species (ROS) in the pancreas of an adult cloned pig leads to apoptosis.     

Which skeletal myoblasts and how to be transplanted for cardiac repair?

Clinical efficacy of skeletal myoblast (skMb) transplantation is controversial whether this treatment produces beneficial outcome in patients with dilated cardiomyopathy (DCM). Based on immunological tolerance between wild-type and DCM hamsters with the deletion of δ-sarcoglycan (SG) gene, skMb engraftment in TO-2 myocardium (3 × 10⁵ cells in ∼100 mg heart) was verified by the donor-specific expression of δ-SG transgene constitutively produced throughout myogenesis. At 5 weeks after the transplantation, the cell rates expressing fast-myosin heavy chain (MHC) exceeded slow-MHC in δ-SG⁺ cells. Fifteen weeks after (corresponding to ∼12 years in humans), fast MHC⁺ cells nullified, but the δ-SG⁺ and slow MHC⁺ cell number remained unaltered. These skMbs fused with host cardiomyocytes via connexin-43 and intercalated disc, modestly improving the hemodynamics without arrhythmia, when engrafted skMbs were sparsely disseminated in autopsied myocardium. These results provide us evidence that disseminating delivery of slow-MHC⁺ myoblasts is promising for repairing DCM heart using histocompatible skeletal myoblasts in future.     

人胎胰巢蛋白阳性细胞的异种体内移植研究

人胎胰巢蛋白阳性(nestin~+)细胞在体外培养中可自发形成类胰岛细胞团(islet-1ike cell cluster,ICC),有多向分化潜能,并可产生分泌胰岛素的类β细胞。为了验证其体内生物学特性和生理功能,我们进行了诱导后ICC的NOD-Scid糖尿病模型小鼠和正常小鼠肾膜下移植,通过免疫细胞化学检测,超微结构观察以及血糖水平监测等手段考察移植后细胞的形态与功能变化情况,结果表明:(1)移植处有明显的血管增生。(2)ICC可使糖尿病模型小鼠血糖明显降低。(3)ICC在正常小鼠体内分化为多种结构,同时继续增殖侵入肾实质。     

家兔供体卵裂球细胞周期对核移植胚胎发育的影响

通过化学药物处理使家兔桑椹胚卵裂球的细胞周期分别同期化于G1、S或G2期 ,然后分别移入去核的MⅡ期卵母细胞中 ,以研究供体核细胞周期对家兔胚胎细胞核移植效率的影响。试验结果表明供体核细胞周期对家兔核移植胚胎的发育潜力有明显影响 ,以G1期卵裂球为供体的核移植重组胚的激活率、卵裂率、桑椹胚、囊胚和孵化囊胚率及囊胚平均细胞数分别为 87 3% (32 2 / 36 9)、 84 9% (2 99/ 35 2 )、 71 5 % (193/ 2 70 )、5 8 0 % (76 / 131)、 35 1% (4 6 / 131)和 12 6± 4 8,显著高于S期 [79 6 % (10 9/ 137)、 74 4% (93/ 12 5 )、30 3% (33/ 10 9)、19 3% (17/ 88)、 6 8% (6 / 88)和 118 8± 3 5 ]、G2期 [6 3 6 % (70 / 110 )、6 0 % (6 0 / 10 0 )、16 9% (11/ 6 5 )、 16 3% (7/ 43)、 4 7% (2 / 43)和 110 6± 5 8]和未经同期化处理的卵裂球 [78 1% (185 /2 37)、 73 2 % (15 8/ 2 16 )、 49 4% (4 3/ 87)、 32 2 % (2 8/ 87)、 12 6 % (11/ 87)和 12 0 5± 4 4](P <0 0 5 )。来源于G1期卵裂球的 144枚克隆胚胎移植到 12只受体中 ,6只妊娠并产下 19只活仔 ,产仔率为 13 2 % ,显著高于来源于S期 (5 8% ,7/ 12 0 )、G2期 (0 ,0 / 12 6 )或未同期化卵裂球的克隆胚胎 (5 3% ,8/ 15 0 ) (P <0     

Kyoto-1保存液保存的移植用肺Ⅱ型肺泡上皮细胞钠-钾泵的研究

目的：临床认为肺水肿已成肺移植过程中的最大障碍。近年来资料表明,过是肺泡液的吸收与Ⅱ型肺泡上皮细胞Na^ 的跨膜能力有关,保存中若能保持肺上Na^ -K^ -ATPase的活性,对成功的肺移植是非常必要的,本实验研究0℃、4℃Kyoto-1（NewET－K）保存液保存体肺脏,型Ⅱ肺泡上皮细胞Na^ -K^ -ATPase的活性变化,为Kyoto-1在临床上最大时限地保存供体肺提供基础理论依据。方法：取Wistar大白鼠,随机分为对照组和实验组,对照组取新鲜肺脏。实验组分别灌注0℃、4℃的Kyoto-1保存液,分别放入0℃、4℃冰箱中保存4h,24h,48h,进行光,电镜酶组织化学研究。使用图像分析系统进行定量测定。结果：4℃、24h实验组钠泵活性可以得到较好的保存（P＞0．05）。结论：钠泵可以作为检测供保存质量的重要指标。     

Selective fluorescence of zymogen granules of pancreatic acinar cells stained with hematoxylin and eosin

Following staining with hematoxylin and eosin Y, paraffin sections of mouse pancreas were examined by transmitted light, epifluorescence and confocal laser scanning microscopy. Light microscopy revealed that the nuclei of pancreatic acinar cells were located basally, while the apices of the cells appeared eosinophilic, although the secretory granules were difficult to visualize. Under violet-blue light excitation, the zymogen granules at the apices of the acinar cells showed strong yellowish fluorescence; the other part of the cytoplasm was only faintly fluorescent and the nuclei and the supporting tissues were nonfluorescent. Confocal laser scanning microscopy resulted in clear pictures of the zymogen granules and their distribution within the cell. The fluorescent emission of zymogen granules was certainly the result of eosin Y staining, because hematoxylin is not a fluorochrome and the zymogen granules are not autofluorescent. Staining with eosin Y alone, however, did not result in clear fluorescent images of zymogen granules or any other cellular structures. Our observation shows that the fluorescence emission of eosin Y allows easy and precise recognition of zymogen granules of pancreatic cells.