Systemic administration of rIL-12 induces complete tumor regression and protective immunity: response is correlated with a striking reversal of suppressed IFN-{gamma} production by anti-tumor T cells

Unfractionated spleen cells taken from tumor-bearing mice 2weeks after tumor implantation contained tumor-primed T cellswhich produced cytokines including IL-2 and IFN- when culturedin vitro. With progressive tumor growth this initial lymphokine-producingcapacity decreased. Here, we investigated the ability of IL-12to (I) restore suppressed IFN- production, (II) cause tumorregression and (II) induce anti-tumor protective immunity. Additionof rIL-12 to spleen cell cultures from 4- to 10-week-old tumor-bearingmice resulted in a striking enhancement in the production ofIFN- compared with cultures of these cells in the absence ofrIL-12 or of normal spleen cells in the presence of rIL-12.Five I.p. injections of rIL-12 into mice bearing s.c. tumorsinduced complete tumor regression. This was found when rIL-12was given at early (1–2 weeks), intermediate (4–5weeks) or even late (7 weeks) stages of tumor growth. Furthermore,IL-12-treated mice which rejected the primary tumor exhibitedcomplete resistance to a rechallenge with the same tumor butdid not reject a second syngenetic tumor. Immunohistochemicalanalyses following IL-12 treatment revealed that CD4⁺ and CD8⁺T cells infiltrate the tumor. More importantly, IFN- mRNA expressionwas observed in fresh tumor masses from tumor-bearing mice receivingIL-12 treatment The importance of IFN- was further demonstratedby the observation that the systemic administration of anti-IFN-mAb prior to IL-12 treatment completely abrogated the anti-tumoreffect of IL-12. Thus, these results indicate that administrationof modest levels of rIL-12 to tumor-bearing mice results intumor regression through mechanisms involving reversal of suppressedIFN- production by anti-tumor T cells and the establishmentof a tumor-specific protective immune response.     

Carboxymethyl-histaminocarbonylmethylamylose as a mimetic system of chymotrypsin in the catalytic hydrolysis of esters

A new type of polysaccharide host, carboxymethyl-histaminocarbonylmethylamylose ( 2b ), containing carboxylic, imidazolyl and hydroxyl groups in the backbone, was used as a mimetic system for chymotrypsin in the catalytic hydrolysis of 3-acetoxy-N-dodecylpyridinium iodide ( 1 ). The substrate is located in the hydrophobic cavity of the amylose helix. The apparent saturation, the entropy-favored kinetics and the pronounced catalytic efficiency (9 times higher than that of a system consisting of the same concentration of carboxymethylamylose and histamine) show that 2b is a good enzyme model in which the definite binding site, active center and self-organization characteristics are present. Most distinctly, the pH-rate constant profile of the hydrolysis of 1 and 2b is of bell-type and has an optimum at pH 7,98, which is very close to 7,90 for chymotrypsin. In conclusion, the charge relay mechanism is also involved in the catalytic effect of 2b .     

基于椭圆方程的三维心脏超声图像的位移场估计

三维超声心动图技术能使医生直观地看到心脏整体和各部分的运动，在临床得到重视。在三维超声心动图技术中，如何定量的描述心脏中某个组织的运动状况极具临床意义。本研究提出了一种基于椭圆偏微分方程的二尖瓣三维运动估计方法。该方法直接在三维超声图像的位移场上进行了运动估计，避免了传统运动估计方法，如光流法，需要标定的缺点。本研究首先建立一个二次误差指标函数，然后利用变分法导出了三维空间下的一组椭圆型偏微分方程。这类方程有着比较成熟的数值解法，利用了有限差分法，对多个三维超声数据立方体进行了计算，结果证明这类方法是有效的。     

胸腰段后髓动脉的起源及其临床意义

目的:为选择性脊髓血管造影和椎管内显微外科提供解剖学资料。方法:采用尸体标本30例,于节段性动脉内逐一注入红色乳胶,在完整脊髓上解剖观察。结果:每例脊髓胸腰段的后髓动脉数目5～13支,平均8.4支。后髓动脉起始情况分3型10亚型,其中后髓动脉与前髓动脉由同一肋间后动脉发出仅34支(13.5％)。胸下部及腰部后髓动脉呈典型“发卡”样折曲。后髓动脉平均外径0.37±0.12mm。约1/3标本在T_(11)～L_3间有1支后髓动脉较粗(>0.5mm),它是脊髓后下部血供的主要来源。结论:多数后髓动脉单独起始,较大的后髓动脉应引起注意。     

肾脏微血管内的压力分布与ANP的作用

本实验在40只大鼠经伺服零测压技术测定的肾脏微血管内压力分布及其ANP的作用均随血管树各段的口径变化而改变。分析小球前各段血管的压力降所占动脉总压降的比例得知:小叶间动脉占总压降的88％。肾小球毛细血管和出球小动脉亦具有较大的压力降。正常对照情况下,肾小球前血管内的压力分布与内径呈直线相关(r=0.869,n=65,P<0.01),其回归方程为平均压()=34.71±0.798×血管内径(D)。给ANP后肾小球前血管内的压力与内径仍呈直线相关(r=0.931,P<0.01),回归方程式为()=38.53+0.765D,其曲线右上移。本文结果提示,肾小球前微血管内压力分布与血管内径密切相关。小叶间动脉的阻力较大。     

Bronchial epithelial-myoepithelial carcinoma

Epithelial-myoepithelial tumor is extremely rare as a pulmonary neoplasm. Only 20 cases have been reported to date, of which 14 were malignant. We report a case of intrabronchial epithelial-myoepithelial carcinoma in a 73-year-old man with a history of heavy smoking. The tumor was well-circumscribed and caused distal airway obstruction. Histologically, the tumor showed glandular and solid architecture. The glands were composed of an inner layer of epithelial cells and an outer layer of myoepithelial cells. The solid areas consisted of spindle-shaped myoepithelial cells. Immunohistochemical staining was positive for p53 and c-Kit (CD117). Focal atypia and increased mitotic activity were present, but no vascular invasion or nodal metastasis was identified.     

Expression of alpha-smooth muscle actin by and contraction of cells derived from synovium

Cells derived from synovium have drawn interest as donor cells for articular cartilage tissue engineering because they have been implicated in certain cartilage repair processes in vivo and the chondrogenic potential of the cells has been demonstrated in vitro. Studies have demonstrated that several other types of musculoskeletal connective tissue cells--including chondrocytes, fibrochondrocytes, ligament fibroblasts and osteoblasts, and mesenchymal stem cells can express the gene for the contractile actin isoform, alpha-smooth muscle actin (SMA), and can contract analogs of extracellular matrix in vitro. Although the physiological roles of SMA-enabled contraction of these cells have yet to be established, cell-mediated contraction of scaffolds employed for tissue engineering can alter the pore diameter of the matrix and distort its overall shape, and thus needs to be addressed. Toward this goal, the objective of this study was to investigate the expression of SMA by synovial cells and to evaluate their contraction of collagen-glycosaminoglycan (GAG) scaffolds. Synovial membranes obtained from the knees (stifle joints) of six adult dogs were evaluated for the presence of SMA by immunohistochemistry. Cells isolated from the synovial tissue were expanded through seven passages in monolayer culture, with samples from each passage allocated for Western blot analysis of SMA. Cells from passage 4 were seeded into porous type I collagen-GAG matrices and cultured for 4 weeks. Synovial cell-mediated contraction of the scaffolds was determined by measuring the diameters of the cell-seeded scaffolds and nonseeded controls every other day. Synovium-derived cells cultured as micropellets or in collagen-GAG matrices were incubated in chondrogenic medium with and without fetal bovine serum and evaluated for chondrogenesis by type II collagen immunohistochemistry. Immunohistochemistry revealed the presence of SMA in some cells (less than 10% of the cells) in the intimal layer of synovium from four of the five animals analyzed. Western blot analysis demonstrated a regular increase in the amount of SMA in the synovium-derived cells with passage number. Synovial cell-mediated contraction of the collagen-GAG scaffolds reached a value of 43% of the original diameter after 4 weeks, comparable to that found with other musculoskeletal cell types. Incubation of micropellet cultures of synovium-derived cells with chondrogenic medium revealed trace amounts of type II collagen production by immunohistochemistry. The findings of this study indicate that control of SMA-enabled contraction may be important when employing synovial cells for cartilage repair procedures, and warrant further investigation into the physiological role of SMA expression in synovial cells.