다중혈관 관상동맥 환자에서 y-문합을 이용하여 양쪽 내흉동맥만을 사용한 우회술의 조기 성적

抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

The 11th edition of Harrison's Principles of Internal Medicine welcomes Anthony Fauci to its editorial staff, in addition to more than 85 new contributors. While the organization of the book is similar to previous editions, major emphasis has been placed on disorders that affect multiple organ systems. Important advances in genetics, immunology, and oncology are emphasized. Many chapters of the book have been rewritten and describe major advances in internal medicine. Subjects that received only a paragraph or two of attention in previous editions are now covered in entire chapters. Among the chapters that have been extensively revised are the chapters on infections in the compromised host, on skin rashes in infections, on many of the viral infections, including cytomegalovirus and Epstein-Barr virus, on sexually transmitted diseases, on diabetes mellitus, on disorders of bone and mineral metabolism, and on lymphadenopathy and splenomegaly. The major revisions in these chapters and many

Harrison's Principles of Internal Medicine

Advanced glycation end products (AGEs) are proteins or lipids that become glycated after exposure to sugars. AGEs are prevalent in the diabetic vasculature and contribute to the development of athe...

Advanced glycation end products: sparking the development of diabetic vascular injury.

Healing of myocardial infarction (MI) requires monocytes/macrophages These mononuclear phagocytes likely degrade released macromolecules and aid in scavenging of dead cardiomyocytes, while mediating aspects of granulation tissue formation and remodeling The mechanisms that orchestrate such divergent functions remain unknown In view of the heightened appreciation of the heterogeneity of circulating monocytes, we investigated whether distinct monocyte subsets contribute in specific ways to myocardial ischemic injury in mouse MI We identify two distinct phases of monocyte participation after MI and propose a model that reconciles the divergent properties of these cells in healing Infarcted hearts modulate their chemokine expression profile over time, and they sequentially and actively recruit Ly-6Chi and -6Clo monocytes via CCR2 and CX3CR1, respectively Ly-6Chi monocytes dominate early (phase I) and exhibit phagocytic, proteolytic, and inflammatory functions Ly-6Clo monocytes dominate later (phase II), have attenuated inflammatory properties, and express vascular–endothelial growth factor Consequently, Ly-6Chi monocytes digest damaged tissue, whereas Ly-6Clo monocytes promote healing via myofibroblast accumulation, angiogenesis, and deposition of collagen MI in atherosclerotic mice with chronic Ly-6Chi monocytosis results in impaired healing, underscoring the need for a balanced and coordinated response These observations provide novel mechanistic insights into the cellular and molecular events that regulate the response to ischemic injury and identify new therapeutic targets that can influence healing and ventricular remodeling after MI

https://rupress.org/jem/article-pdf/204/12/3037/1160364/jem_20070885.pdf

The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions

Within tumours, many non-neoplastic cells such as fibroblasts, endothelial cells, and macrophages assist tumour growth by producing various growth factors and pro-angiogenic cytokines. Various tumour-derived molecules drive tumour-associated macrophages towards an anti-inflammatory phenotype (M2) and thus promoting tumour growth. Here we investigated microglia/macrophage differentiation in glioma tissues by means of immunostaining of paraffin-embedded glioma samples. The number of microglia/macrophages with positive staining for CD163 and CD204, which are believed to be markers for M2 macrophages, was correlated with the histological grade of the gliomas. The ratio of M2 macrophages in the tumour-associated microglia/macrophages was also associated with the histological grade. Culture supernatant from the glioma cell line can stimulate macrophages to develop into the M2 phenotype in vitro. Macrophage colony-stimulating factor (M-CSF), which strongly induces M2 polarization of macrophages, was significantly correlated with histological malignancy and with the proportion of M2 microglia/macrophages in vivo. In addition, the proportion of M2 microglia/macrophages and M-CSF expression in tumour cells correlated well with proliferation of glioblastoma cells. These results suggest that tumour-derived M-CSF induces a shift of microglia/macrophages towards the M2 phenotype, which influences tumour growth. Evaluation of the proportion of M2 microglia/macrophages and M-CSF expression in tumour tissue would be useful for assessment of microglia/macrophage proliferative activity and the prognosis of patients with gliomas.

Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas

Tumor-associated macrophages: Potential therapeutic targets for anti-cancer therapy.

The fact that various immune cells, including macrophages, can be found in tumor tissue has long been known. With the recent introduction of the novel concept of macrophage differentiation into a classically activated phenotype (M1) and an alternatively activated phenotype (M2), the role of tumor-associated macrophages (TAMs) is gradually beginning to be elucidated. Specifically, in human malignant tumors, TAMs that have differentiated into M2 macrophages act as “protumoral macrophages” and contribute to the progression of disease. Based on recent basic and preclinical research, TAMs that have differentiated into protumoral or M2 macrophages are believed to be intimately involved in the angiogenesis, immunosuppression, and activation of tumor cells. In this paper, we specifically discuss both the role of TAMs in human malignant tumors and the cell–cell interactions between TAMs and tumor cells.

/pdf/clinical-significance-of-macrophage-heterogeneity-in-human-14pzui0ibm.pdf

Clinical significance of macrophage heterogeneity in human malignant tumors

A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice.

Many studies have shown that tumor-associated macrophages (TAMs) contribute to tumor development and poor prognosis in various cancers. In this study, we investigated the macrophage populations and phenotypes, and their correlation to angiogenesis, immunosuppression, and clinical prognosis in intrahepatic cholangiocarcinoma (ICC). CD68 (+) and CD163 (+) macrophage infiltration was analyzed in paraffin-embedded tissue samples from 39 patients. CD163 is used as a marker of M2 macrophages. Neovascularization and infiltration of forkhead box P3 (FOXP3) (+) regulatory T cells were also evaluated. The number of CD68 (+) and CD163 (+) macrophages was positively correlated with the numbers of vessels and regulatory T cells. The number of CD163 (+) cells was more closely associated with them. Intrahepatic cholangiocarcinoma (ICC) patients with high counts of CD163 (+) macrophages showed poor disease-free survival (P = 0.0426). The macrophage density was not correlated with overall survival. In an in vitro study using ICC cell lines (HuCCT1, RBE, and MEC) and human macrophages, tumor cell supernatant (TCS) from cell lines induced an activation of signal transducers and activators of transcription-3 (Stat3) and macrophage polarization toward the M2 phenotype. Tumor cell supernatant (TCS) from HuCCT1 most strongly induced Stat3 activation and production of cytokines and other bioactive molecules such as interleukin (IL)-10, vascular endothelial growth factor (VEGF)-A, transforming growth factor (TGF)-beta, and matrix metalloproteinase (MMP)-2. Down-regulation of Stat3 by siRNA significantly suppressed the production of IL-10 and VEGF-A. These results provide suggestive evidence that TAMs contribute to cancer progression via Stat3 activation, and CD163 is useful for evaluating M2 TAMs and predicting the clinical prognosis of ICC patients.

https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1349-7006.2010.01614.x

Motohiro Takeya

Papers

Possible involvement of the M2 anti-inflammatory macrophage phenotype in growth of human gliomas

Tumor-associated macrophages: Potential therapeutic targets for anti-cancer therapy.

Clinical significance of macrophage heterogeneity in human malignant tumors

A dipeptidyl peptidase-4 inhibitor, des-fluoro-sitagliptin, improves endothelial function and reduces atherosclerotic lesion formation in apolipoprotein E-deficient mice.

Significance of alternatively activated macrophages in patients with intrahepatic cholangiocarcinoma