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

Recent data have expanded the concept that inflammation is a critical component of tumour progression. Many cancers arise from sites of infection, chronic irritation and inflammation. It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration. In addition, tumour cells have co-opted some of the signalling molecules of the innate immune system, such as selectins, chemokines and their receptors for invasion, migration and metastasis. These insights are fostering new anti-inflammatory therapeutic approaches to cancer development.

Inflammation and cancer

Statistical method for testing the neutral mutation hypothesis by DNA polymorphism.

Integrins: versatility, modulation, and signaling in cell adhesion.

The categorization of individuals into groups can serve some useful purposes. If the individuals being grouped are heterogeneous, however, the categories used are likely to be flawed. Thus, any resulting generalizations are also flawed, especially when applied to a given individual in a group. The most serious attendant dangers can be misplaced pride, misguided prejudice, and unfair discrimination. The categorization of physicians according to their original medical training and the generalizations that result are examined here. The principles advanced could also be applied to many other forms of categorization.

Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual.

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.

/pdf/sialoglycan-recognition-is-a-common-connection-linking-1bs48gcz06.pdf

Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis.

Provided herein are glycosylated polypeptide compositions with substantially reduced Neu5Gc content. The glycosylated polypeptides compositions with substantially reduced Neu5Gc content can be obtained from cell sources cultured with Neu5Gc competitor or from non-human animal sources fed a diet supplemented with Neu5Gc competitor. Also provided herein are methods of treating a human subject with said compositions.

Novel glycosylated polypeptides

Exploring the Biological Roles of Glycans

Publisher Summary This chapter focuses on the glycoprotein sialate 7(9)-O-acetyltransferase from rat liver golgi vesicles. Although the vesicles are impermeant to acetate, free [3H] acetate also accumulates inside the vesicles during this labeling reaction. This occurs mainly as a by-product of the acetylation reaction itself, and not from the action of an acetyl-CoA hydrolase. A smaller proportion of the free [3H] acetate arises from the action of an 9-O-acetylesterase activity present in the same vesicles. Ester groups added to the 7-position can subsequently undergo migration to the 9-position, if it is not already acetylated. No evidence was found in rat liver for a mutase that could catalyze this migration reaction.

Ajit Varki

Papers

Of pride, prejudice, and discrimination. Why generalizations can be unfair to the individual.

Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis.

Novel glycosylated polypeptides

Exploring the Biological Roles of Glycans

Glycoprotein sialate 7(9)-O-acetyltransferase from rat liver Golgi vesicles.