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.

Useful information about glycoconjugates can be obtained by labeling their aglycone (noncarbohydrate) portions—e.g., labeling proteins with radioactive amino acids—and then using techniques described elsewhere in this chapter to infer the presence, type, and nature of glycan chains. This unit describes metabolic labeling techniques that provide more specific information about the structure, sequence, and distribution of the sugar chains of glycoconjugates. Following metabolic labeling, the radioactive glycoconjugate of interest is isolated, individual glycosylation sites are identified and separated if necessary, and the labeled glycans are subjected to structural analysis. Curr. Protoc. Protein Sci. 57:12.2.1-12.2.15. C � 2009 by John Wiley & Sons, Inc.

Metabolic Radiolabeling of Animal Cell

Clinical evidence for a more active immune response in humans compared with our closest hominid relative, the chimpanzee, includes the progression of HIV infection to AIDS, hepatitis B– and C–related inflammation, autoimmunity, and unwanted harmful immune responses to viral gene transfer vectors. Humans have a unique mutation of the enzyme CMP-N-acetylneur-aminic acid hydroxylase (CMAH), causing loss of expression of the sialic acid Neu5Gc. This mutation, occurring 2 million years ago, likely altered the expression and function of ITIM-bearing inhibitory receptors (Siglecs) that bind sialic acids. Previous work showed that human T cells proliferate faster than chimpanzee T cells upon equivalent stimulation. In this article, we report that Cmah 2/2 mouse T cells proliferate faster and have greater expression of activation markers than wild-type mouse T cells. Metabolically reintroducing Neu5Gc diminishes the proliferation and activation of both human and murine Cmah 2/2 T cells. Importantly, Cmah 2/2 mice mount greater T cell responses to an adenovirus encoding an adeno-associated virus capsid transgene. Upon lymphocytic choriomeningitis virus infection, Cmah 2/2 mice make more lymphocytic choriomeningitis virus–specific T cells than WT mice, and these T cells are more polyfunctional. Therefore, a uniquely human glycosylation mutation, modeled in mice, leads to a more proliferative and active T cell population. These findings in a human-like mouse model have implications for understanding the hyperimmune responses that characterize some human diseases. M ammalian cells are coated with a complex layer of glycans that mediate pathogen binding, cell adhesion, cell trafficking, cell signaling, endocytosis, apoptosis, and proliferation (1). Although heterogeneity in the expression and structure of these glycan chains can exist within the same individual and even within the same organ, an interesting species-specific divergence in these sugars was discovered in 1998. Two groups reported the human-specific inactivating mutation of the enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH), which is responsible for the conversion of sialic acid precursor CMP-Neu5Ac to CMP-Neu5Gc by the addition of a single hydrogen atom (2, 3). As a result, Neu5Gc is not synthesized in human cells and is, in fact, immunogenic (4, 5). This mutation appears to have set in motion a series of genetic and biochemical changes in the biology of sialic acids that may contribute to several unique aspects of human biology in health and disease (6, 7). Of the many functions that sialic acids play in cellular physiology , their role as ligands of inhibitory Siglecs is well recognized. Siglecs, or sialic …

of Human Glycosylation Enhanced T Cell Function in a Mouse Model

Thank you for asking me to comment on the article by Schnaar and Freeze entitled “A ‘Glyconutrient Sham’,” which addresses a serious matter affecting the field of glycobiology. I will not reiterate most of the major issues, as they have been thoroughly documented in the article. Rather, I will focus on the overarching moral imperative that trumps all the others. Regardless of who is right or wrong about any of the issues, it appears that many desperately ill patients and parents of children with serious chronic disorders are being misled. A recent related news article in Science (Kaiser, 2007) focused on the conflict, but did not emphasize what might be the motivation of scientists who have taken such a stand against commercial interests. The answer lies not just in the lack of evidence for definite health benefits of a mixture of apparently indigestible plant polysaccharides that are not derived from any known traditional medicines. The predominant reason is the many contacts that academic glycobiologists like myself have had from desperate patients and their families and friends, regarding extravagant claims for therapeutic efficacy made by sales associates. Like others, I have spent time responding to such queries, some of which seem to involve patients denying themselves known effective and standardized therapies for serious diseases. Together with false hopes given to families of other patients with incurable chronic diseases, the situation impels taxpayer-funded scientists like myself to speak out. As Kaiser concludes in her Science article, “health claims must be based on solid science.”

/pdf/letter-to-the-glyco-forum-25qoehmkg8.pdf

Letter to the Glyco-Forum

Functional Adaptation in a Sialic Acid-binding Receptor sialic acid/Siglec/human evolution/domain-specific adaptation/comparative biology

Chemical biology, an integration of multiple fields When the Nobel Prizes were first created in 1901 to honor major progress in various domains of human knowledge, the awards for scientific progress could be roughly classified by levels of certainty, with physics and chemistry having apparently immutable laws in the known universe, and physiology and medicine having less precision. But bridging disciplines, such as organic chemistry, biochemistry, molecular biology, and cell biology, were still in their infancy, and the overarching principles of evolutionary biology were not yet established. We are now in an era wherein these previously distinct disciplines are overlapping and merging, and chemical biology (application of chemical techniques, analysis, and compounds to study and manipulate biological systems) is receiving much attention. Remarkable and practically relevant examples were recognized with the 2022 Nobel Prize in Chemistry, which was awarded to Morten Meldal and K. Barry Sharpless for the development of “click chemistry” and to Carolyn R. Bertozzi for the concept of “bioorthogonal chemistry.” Meldal and Sharpless developed fast-rate copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC, referred to herein as click) reactions, which have found broad applications in various fields for different purposes (1). This brief Viewpoint focuses on Bertozzi’s groundbreaking bioorthogonal chemistry concept. Berozzi coined the term to refer to any chemical reaction that can occur inside of living systems without interfering with native biochemical processes (2) and led the advances in developing such reactions and applying them in vivo. These user-friendly chemical reactions, reagents, and tools are critical for exploring the functions and applications of target molecules, especially those in living systems, and they expand the applications of chemical biology to better understand and treat human disease.

Ajit Varki

Papers

Metabolic Radiolabeling of Animal Cell

of Human Glycosylation Enhanced T Cell Function in a Mouse Model

Letter to the Glyco-Forum

Functional Adaptation in a Sialic Acid-binding Receptor sialic acid/Siglec/human evolution/domain-specific adaptation/comparative biology

User-friendly bioorthogonal reactions click to explore glycan functions in complex biological systems