Prognosis for polypoidal melanoma is determined by primary tumor thickness

Survival of 23 patients with polypoidal malignant melanomas was compared with an identical number of patients with nonpolypoidal melanomas of similar thickness, stage, and location. Five-year survivals for the two groups were not significantly different. The dominant prognostic factor leading to the adverse prognosis associated with polypoidal melanomas was the primary tumor thickness (all greater than 1.70 mm) and not the polypoidal morphologic configuration per se.     

Effects of anti-C5a antibodies on the adult respiratory distress syndrome in septic primates.

In vitro and in vivo studies have suggested that human complement component C5a plays a key role in neutrophil injury in the adult respiratory distress syndrome (ARDS). First, using leukocyte aggregometry, we demonstrated that the addition of a recently developed rabbit anti-human polyclonal antibody to C5a des arg to endotoxin-activated plasma prevented leukocyte aggregation in vitro. We then administered the anti-C5a des arg antibody to septic primates (Macaca fascicularis). Three groups of primates, control, septic, and anti-C5a antibody treated septic, were studied (n = 4 in each group). A 30-min infusion of Escherichia coli (1 X 10(10)/kg) resulted in severe sepsis and ARDS. Primates were killed 4 h after completion of the E. coli infusion. Septic animals not treated with anti-C5a antibody had 75% mortality (3/4), decreased oxygenation, severe pulmonary edema, and profound hypotension. Septic primates treated with anti-C5a antibodies did not die and did not develop decreased oxygenation (P less than 0.05) or increased extravascular lung water (P less than 0.05). They also had a marked recovery in their mean arterial blood pressure (P less than 0.05). This study demonstrates that treatment with rabbit anti-human C5a des arg antibodies attenuates ARDS and some of the systemic manifestations of sepsis in nonhuman primates.     

Caudal-posteroanterior view in coronary arteriography

Posteroanterior (PA) and caudally angulated PA views were obtained in 20 patients undergoing routine coronary arteriography. Although the left main coronary artery (LMCA) was seen well on both views in all patients, the PA-caudal view improved depiction of the LMCA bifurcation in 15 (75%). In addition, the PA-caudal view markedly improved depiction of the circumflex artery, affording optimal depiction of this artery and its branches in 78%-89% of patients. Neither the PA nor the PA-caudal view allowed adequate depiction of the left anterior descending artery. Thus, the PA-caudal view should supplant the PA view in routine coronary arteriography.     

Application of immunohistochemistry in the differential diagnosis of skin tumors

As with neoplasms in any tissue, skin tumors may be categorized as epithelial or mesenchymal, benign or malignant, and primary or metastatic. Immunoperoxidase stains are useful in elucidating the nature of the tumor cells, especially in poorly differentiated tumors. It is important to consider that tumors may exhibit staining patterns different from the typical or reported results. This may be because of intrinsic features of the neoplasm such as the aberrant expression of antigens (markers). Furthermore, the staining of the tumor may be affected by tissue preservation and fixation as well as by the selection of antibodies used for staining. For this reason, the pathologist should be vigilant in comparing the results of unknown tumors with standard controls, with results in the literature, and with his or her own experience. Unusual neoplasms may require additional tissue for analysis, study by other ancillary methods such as electron microscopy, or consultation by more experienced laboratories. These guidelines should be helpful in providing accurate diagnosis of skin tumors.     

低血糖指数膳食改善超重老年糖尿病患者氧化应激水平

目的:观察低血糖指数的膳食对2型糖尿病患者氧化应激状态的影响。方法:2004-10/11在上海市静安区二个社区卫生服务中心招募受试者,经医生明确诊断为2型糖尿病、病程超过6个月,体质量指数≥24kg/m2的老年糖尿病志愿者43名,受试者对试验知情同意。采用随机交叉试验随机分配至低血糖指数饮食组和高血糖指数饮食组,每种膳食分别连续使用4周,间隔洗脱期4周,比较试验前后患者超氧化物歧化酶、脂质过氧化产物丙二醛和谷胱甘肽过氧化物酶含量的变化。结果:受试者依从性好,除1人因试验期间发现肿瘤而退出试验,42名志愿者按设计要求完成试验。膳食干预后低血糖指数饮食组和高血糖指数饮食组的超氧化物歧化酶活力分别升高了15.68%和21.33%,丙二醛水平分别下降23.94%和21.55%,谷胱甘肽过氧化物酶活力分别升高了15.74%和17.09%;干预后低血糖指数饮食组丙二醛下降水平与高血糖指数饮食组比较差异有显著性意义(P<0.05),而超氧化物歧化酶和谷胱甘肽过氧化物酶活性两组间差异无显著性意义(P>0.05)。结论:在控制总能量的基础上给予平衡膳食能够改善其氧化应激水平,采用低血糖指数食物有助于氧化应激水平的改善。     

机械力学对体外骨髓间充质干细胞的影响

目的:分析力学刺激体外骨髓间充质干细胞所产生增殖分化等生物学效应的影响及其力化学信号转导途径。资料来源:因特网上检索PubMed数据库中2000-01/2006-06期间有关力学刺激对骨髓干细胞作用效应进展的英文文章,检索词“stem cel1,marrow mesenchymal stem cells,mechanical stimulation,stress”,同时检索CNKI中国知网医学文献数据库2000-01/2006-06期间的相关文章,检索词为“干细胞、骨髓间充质干细胞、机械刺激、应力”。资料选择:对资料进行筛选,选取相关文章查找全文。纳入标准:①骨髓间充质干细胞相关生物学特性。②体外细胞加载的应力分类及相应力学装置的特点。③应力对细胞影响的研究。④能获取文章的全文。排除标准:①较陈旧的文献。②重复研究。资料提炼:共收集关于86篇体外骨髓干细胞及力学干预的相关文献。其中30篇符合纳入标准。资料综合:①骨髓干细胞具有高度增殖及多向分化能力,可通过体外培养、干预作为细胞组织工程的理想种子细胞。②力学刺激是体外调节细胞生物学效应的重要途径,其中力学分类有:流体切应力、静止压应力、张应力、离心力以及单个细胞的吸吮力等,介绍各种力以及相应的力学装置的特点。③骨髓干细胞加载各种应力干预后产生的生物学效应,以及细胞应力学刺激的机制、信号转导途径。结论:力学刺激可影响骨髓间充质干细胞生物学特性,在适当的力学刺激条件下,促进细胞的增殖与分化,为骨组织工程提供新的技术手段,同时也为临床应用牵拉成骨的骨再生过程提供理论依据。     

MFG-E8-mediated uptake of apoptotic cells by APCs links the pro- and antiinflammatory activities of GM-CSF

Granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances protection against tumors and infections, but GM-CSF-deficient mice develop inflammatory disease. Here we show that GM-CSF is required for the expression of milk fat globule EGF 8 (MFG-E8) in antigen-presenting cells, and that MFG-E8-mediated uptake of apoptotic cells is a key determinant of GM-CSF-triggered tolerance and immunity. Upon exposure to apoptotic cells, GM-CSF-deficient antigen-presenting cells (APCs) produce an altered cytokine profile that results in decreased Tregs and increased Th1 cells, whereas concurrent ablation of IFN-gamma promotes Th17 cells. In wild-type mice, MFG-E8 attenuates the vaccination activity of GM-CSF-secreting tumor cells through Treg induction, whereas a dominant-negative MFG-E8 mutant potentiates GM-CSF-stimulated tumor destruction through Treg inhibition. These findings clarify the immunoregulatory effects of apoptotic cells and suggest new therapeutic strategies to modulate CD4(+) T cell subsets in cancer and autoimmunity.     

Fibroblast growth factor 2 decreases bleomycin‐induced pulmonary fibrosis and inhibits fibroblast collagen production and myofibroblast differentiation

Fibroblast growth factor (FGF) signaling has been implicated in the pathogenesis of pulmonary fibrosis. Mice lacking FGF2 have increased mortality and impaired epithelial recovery after bleomycin exposure, supporting a protective or reparative function following lung injury. To determine whether FGF2 overexpression reduces bleomycin‐induced injury, we developed an inducible genetic system to express FGF2 in type II pneumocytes. Double‐transgenic (DTG) mice with doxycycline‐inducible overexpression of human FGF2 (SPC‐rtTA;TRE‐hFGF2) or single‐transgenic controls were administered intratracheal bleomycin and fed doxycycline chow, starting at either day 0 or day 7. In addition, wild‐type mice received intratracheal or intravenous recombinant FGF2, starting at the time of bleomycin treatment. Compared to controls, doxycycline‐induced DTG mice had decreased pulmonary fibrosis 21 days after bleomycin, as assessed by gene expression and histology. This beneficial effect was seen when FGF2 overexpression was induced at day 0 or day 7 after bleomycin. FGF2 overexpression did not alter epithelial gene expression, bronchoalveolar lavage cellularity or total protein. In vitro studies using primary mouse and human lung fibroblasts showed that FGF2 strongly inhibited baseline and TGFβ1‐induced expression of alpha smooth muscle actin (αSMA), collagen, and connective tissue growth factor. While FGF2 did not suppress phosphorylation of Smad2 or Smad‐dependent gene expression, FGF2 inhibited TGFβ1‐induced stress fiber formation and serum response factor‐dependent gene expression. FGF2 inhibition of stress fiber formation and αSMA requires FGF receptor 1 (FGFR1) and downstream MEK/ERK, but not AKT signaling. In summary, overexpression of FGF2 protects against bleomycin‐induced pulmonary fibrosis in vivo and reverses TGFβ1‐induced collagen and αSMA expression and stress fiber formation in lung fibroblasts in vitro, without affecting either inflammation or epithelial gene expression. Our results suggest that in the lung, FGF2 is antifibrotic in part through decreased collagen expression and fibroblast to myofibroblast differentiation. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Effect of heparinization of catheters on pulmonary artery oximetry

A clinical study was performed in two phases to determine whether pulmonary artery oximeter catheters that were impregnated or bonded with heparin would affect the accuracy of measurements of in vivo mixed venous oxygen saturation (S O₂). In phase 1, 40 patients were catheterized with either a heparin-impregnated or a plain pulmonary artery catheter. Blood was sampled at random times to correlate in vivo with in vitro S O₂ measurements. In phase 2, 16 patients who were not receiving systemic heparin therapy or aspirin and who had no coagulopathies were catheterized with either a heparin-bonded or a plain pulmonary artery catheter in a blinded order. In phase 1, a total of 364 blood samples were obtained from 40 patients. Linear regression analysis of the pooled data demonstrated y=0.98x–0.01,r=0.93,P<0.001, andn=141 with heparin-impregnated catheters; and y=0.87x+8.0,r=0.81,P<0.001, andn=223 with plain catheters. The mean difference (in vivo minus in vitro) revealed a similar error (–1.3±0.4 versus –1.4±0.4, respectively, mean±SE). The 95% confidence limits of an individual value (±8.1 versus ±12.3) suggested slightly greater accuracy with heparin-impregnated catheters. In phase 2, a total of 134 blood samples were obtained from 16 patients. Linear regression analysis showed nearly equal performance with heparin-bonded and plain catheters (r=0.97 versusr=0.98, respectively) with similar slopes (1.0 versus 1.1, respectively) but different intercepts (–0.6 versus –8.4, respectively). Analysis of the mean difference revealed a measurement error of 0.4±0.3 versus –1.3±0.3 with similar 95% confidence limits of individual values (±5.0 versus ±4.8, respectively). These differences do not appear clinically important. These data suggest that heparinization only minimally enhanced accuracy with a pulmonary artery oximetry system, which accurately measured S O₂ to within 3 to 4% of true values.