Structure-activity studies with chiral isomers and with segments of the antimitotic marine peptide dolastatin 10

Eighteen configurational isomers of the antimitotic peptide dolastatin 10 (Bai et al., Biochem Pharmacol 39: 1941-1949, 1990) derived from Dolabella auricularia, together with segments obtained as precursors in its synthesis (Pettit et al., J Am Chem Soc 111: 5463-5465, 1989), were examined as inhibitors of tubulin polymerization and as inhibitors of growth of L1210 murine leukemia cells in culture. Dolastatin 10 consists of four amino acids (in order from the amino terminus: dolavaline, valine, dolaisoleucine, and dolaproine), three unique to D. auricularia, linked to an unusual primary amine (dolaphenine, probably derived from phenylalanine) at what would otherwise be its carboxyl terminus. Dolastatin 10 has nine asymmetric carbon atoms, and available isomers included alternate configurations at five positions (positions 9 and 10 in the dolaproine moiety and positions 18, 19 and 19a in the dolaisoleucine moiety). For tubulin polymerization, only alterations at positions 18 and 19 resulted in loss of inhibitory activity of the isomer. In addition, a tripeptide containing dolavaline, valine and dolaisoleucine with all asymmetric carbons identical configurationally to those in dolastatin 10 was found to be about 30% as effective as dolastatin 10 in inhibiting tubulin polymerization. Cytotoxic effects were much more sensitive to alterations in the dolastatin 10 structure. The only modification which did not lead to reduced cytotoxicity was reversal of configuration at position 19a in the dolaisoleucine moiety. Both this isomer and dolastatin 10 had IC50 values of less than 1 nM. Several other isomers had IC50 values with the L1210 cells in the range of 30-90 nM, but these did not correlate well with their inhibitory effects on tubulin polymerization. The tripeptide effective as an inhibitor of tubulin polymerization had no activity against the L1210 cells.     

阴股沟皮瓣显微解剖学特征及其在组织修复功能重建中的应用

目的：明确阴股沟皮瓣的显微解剖基础，为临床应用此皮瓣提供解剖依据。资料来源：应用计算机检索Medline1991-01／2005-01的相关文章，检索词“pudendal-thigh flap，micranatomy”，并限定文章语言种类为English。并且手工检索《中文科技资料目录一医药卫生）1998-01／2005-01的相关文章，检索途径：分类途径。 资料选择：对资料进行初审，并查看每篇文献后的引文。纳入标准：①随机对照的基础及临床试验。②无论是否为单盲，双盲或非盲法。排除标准：重复性研究或综述性文章。 资料提炼：共检索到42篇相关文章，21篇文献符合纳入标准，排除的21篇文献为内容陈旧或重复。 资料综合：阴股沟区动脉血液供应充足，并且位置均比较恒定，尤以阴部外动脉最为恒定。静脉回流丰富，神经支配可靠。阴股沟皮瓣是位于股内侧上方与会阴部之间的无毛区域，上界平耻骨联合上缘水平，下界为两侧坐骨结节连线，内侧界为阴囊或大阴唇外侧缘，外侧界为股内侧皱襞，自阴囊（唇）外侧缘向大腿内上方延伸约5cm包括的范围。该区动脉血液供应丰富，计有阴部外动脉，闭孔动脉前皮支，阴囊（唇）后动脉的外侧支，旋股内侧动脉的皮支，股内侧的主要动脉支，以及来自阴部内动脉的肛动脉（直肠下动脉）等，并且位置均比较恒定，其中尤其以阴部外动脉最为恒定。在阴股沟区，阴囊（唇）后动脉与旋股内动脉、闭孔动脉前支及阴部外动脉的分支存在广泛的吻合并在内收肌内侧以上的深筋膜层形成血管网。进入阴股沟区的多支血管相互吻合成网。阴股沟区静脉回流丰富，神经支配可靠。 结论：阴股沟皮瓣血运丰富，解剖简便易行，切取方便，供区隐蔽，再造性器官外形及恢复神经感觉均取得较为理想的效果，是一种值得推广的方法。     

Pre-Implantation Multiple Cytokine mRNA Expression Analysis of Donor Lung Grafts Predicts Survival After Lung Transplantation in Humans

While current donor selection with clinical findings is generally effective, the imprecise nature of the assessment forces clinicians to remain on the conservative side. A reliable biological marker would assist donor selection and would improve donor organ utilization. We collected biopsies from 169 donor lungs before implantation. Expression levels of IL-6, IL-8, IL-10, TNF-alpha, IFN-gamma and IL-1beta were measured by quantitative real-time RT-PCR (qRT-PCR). Seventeen cases died within 30 days after transplantation. No donor factor was significantly associated with 30-day mortality. Univariate analysis of the 84 cases for development of the prediction model showed that IL-6, IL-8, TNF-alpha and IL-1beta were risk factors for mortality and IL-10 and IFN-gamma were protective factors. We analyzed the cytokine expression ratios of risk to protective cytokines. A stepwise logistic regression for 30-day mortality demonstrated that a model containing the ratio of IL-6/IL-10 was the most predictive (p = 0.0013). When applied to the remaining 85 cases for validation, the test of model fit was significant (p = 0.039). Using the cytokine ratio, we were able to define three risk groups with striking differences in survival (p = 0.0003). Multi-cytokine analysis of the donor lung graft with qRT-PCR shows significant promise as a strategy to biologically evaluate the donor lung prior to implantation.     

哺乳期营养对室间隔心肌细胞发育的影响——游离心肌细胞的形态测量

在心肌细胞分化性生长时期,改变新生鼠的哺乳期营养条件对这些鼠的空间隔心肌细胞将会产生暂时性作用和持久性影响。哺乳期高营养的暂时性作用是增加空间隔心肌细胞的大小和数量;而低营养的暂时性作用则是减慢室间隔心肌细胞的生长。哺乳期高营养的持久性作用是限制室间隔心肌细胞的过度肥大;而低营养则促进成熟鼠的室间隔心肌细胞的过度肥大。     

A Bayesian iterative transmission gradient reconstruction algorithm for cardiac SPECT attenuation correction

Background  High-quality attenuation maps are critical for attenuation correction of myocardial perfusion single photon emission computed tomography studies. The filtered backprojection (FBP) approach can introduce errors, especially with low-count transmission data. We present a new method for attenuation map reconstruction and examine its performance in phantom and patient data. Methods and Results  The Bayesian iterative transmission gradient algorithm incorporates a spatially varying gamma prior function that preferentially weights estimated attenuation coefficients toward the soft-tissue value while allowing data-driven solutions for lung and bone regions. The performance with attenuation-corrected technetium 99m sestamibi clinical images was evaluated in phantom studies and in 50 low-likelihood patients grouped by body mass index (BMI). The algorithm converged in 15 iterations in the phantom studies. For the clinical studies, soft-tissue estimates had significantly greater uniformity of mediastinal coefficients (mean SD, 0.005 cm⁻¹ vs 0.011 cm⁻¹; P<.0001). The accuracy and uniformity of the Bayesian iterative transmission gradient algorithm were independent of BMI, whereas both declined at higher BMI values with FBP. Attenuation-corrected perfusion images showed improvement in myocardial wall variability (4.8% to 4.1%, P=.02) for all BMI groups with the new method compared with FBP. Conclusion  This new method for attenuation map reconstruction provides rapidly converging and accurate attenuation maps over a wide spectrum of patient BMI values and significantly improves attenuation-corrected perfusion images.     

4-1BB(CD137)配体在几种肿瘤细胞株上的表达

目的：研究4—1BBL在几种人肿瘤细胞株上的表达。方法：用RT—PCR及法检测肿瘤细胞内4—lBBL mRNA水平的表达；用流式细胞仪检测肿瘤细胞膜表面4—1BBL的表达。结果：4—1BBL在Jurkat细胞株上高表达(98．97％)，在HL-60和K562上表达较低(分别为24．77％和19．23％)，而在HL-29细胞株上基本不表达(2．13％)。结论：4—1BBL在不同肿瘤细胞株表达水平不同。     

血清铁和铁蛋白与肝病患者肝纤维化指标的关系

OBJECTIVE: To study the relationship of serum iron and ferritin with the indicators for hepatic fibrosis and hepatic iron overload. METHODS: Liver tissue specimens were obtained from 41 patients with benign (16) or malignant (25) liver diseases by 1 second liver biopsy, and routine microscopic examination was performed after haematoxylin-eosin (HE) and Perl's Prussian staining. Atomic absorption spectrum, radioimmunoassay and enzyme-linked immunosorbent assay were respectively employed to examine the serum levels of iron, ferritin, hyaluronic acid, laminin, human procollagen type , and collagen type . RESULTS: Between patients with benign and malignant liver diseases, significant differences were found in the serum ferritin levels (P < 0.05), but not in serum iron levels (P > 0.05). It was also noted that the levels of the indicators for hepatic fibrosis in patients with benign and early-stage malignant diseases varied significantly from the levels in normal subjects, but these differences were not observed between normal subjects and patients with end-stage hepatic malignancies. Serum iron and ferritin were found to be associated with serum laminin levels (serum iron: r=0.439, P=0.031; serum ferritin: r=0.476, P=0.016), and no iron granules detected in the tissue specimens of hepatocellular carcinoma. CONCLUSIONS: Most of the patients with hepatocellular carcinoma have elevated serum ferritin levels. The serum levels of iron and ferritin are statistically correlated with serum laminin level. Obvious reduction of iron content is typical of hepatic malignant tissues in comparison with the benign tissues, and the reduction in the levels of the indicators for hepatic fibrosis might involve the inhibition of collagen synthesis in the tumor tissues from patients with end-stage hepatocellular carcinoma. Most of the cases of alcoholic fatty liver are complicated by liver iron overload, often marked by serum iron and ferritin levels.     

膀胱出口梗阻后逼尿肌收缩蛋白表达和膀胱重量的改变

目的探讨膀胱出口梗阻(BOO)后逼尿肌收缩蛋白表达和膀胱重量的改变及意义。方法BOO组病人16例,筛选条件为入院诊断良性前列腺增生症(BPH)并经尿动力学压力-流率检查证实为高压低流型;对照组5例,为外伤等情况入院并排除有下尿路梗阻病史者。BOO组所有病例均行耻骨上经膀胱前列腺摘除术,术前B超检查测定膀胱重量和前列腺内外径比值,术中切取膀胱上壁组织2cm×1cm×1cm大小,标本行RT-PCR反应,检测膀胱逼尿肌中肌动蛋白和肌球蛋白mRNA的表达,并比较其与膀胱重量间的线性相关性。结果BOO组与对照组膀胱重量分别为(92.15±34.89)g和(56.08±20.35)g,(P<0.05);前列腺内外径比值分别为(0.57±0.16)和(0.18±0.06),(P<0.01);与对照组相比,BOO组肌动蛋白和肌球蛋白mRNA的表达量均有显著增加,分别为(40.32±59.67)×106和(6.59±5.62)×106,(P值均<0.01);且两者表达量与膀胱重量之间均有明显线性正相关性(P<0.05)。结论逼尿肌中肌动蛋白和肌球蛋白的表达与膀胱逼尿肌的功能状态密切相关。     

对侧网状巨细胞核对大鼠脊髓背表面电位的影响

以浅麻醉和麻痹大鼠为对象,利用计算机平均技术记录强电流刺激腓肠神经诱发的脊髓背表面电位(CDP),观察对侧网状三细胞核(NGC)微量注射L一谷氨酸钠,使神经细胞兴奋后对CDP的影响.实验发现,对侧NGC神经细胞兴奋后,Aβ和Aσ纤维引起的P_1波及Aσ和C类纤维引起的N_3波减小,C类纤维引起的P_2波明显减小,N_4 波消失.以上结果提示:对侧NGC对细纤维诱发的CDP成分有抑制作用.