https://cancerbiologyprogram.med.wayne.edu/pdfs/hallmarks_cancer_article.pdf

Hallmarks of cancer: the next generation.

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

Background Hyperglycemia and insulin resistance are common in critically ill patients, even if they have not previously had diabetes. Whether the normalization of blood glucose levels with insulin therapy improves the prognosis for such patients is not known. Methods We performed a prospective, randomized, controlled study involving adults admitted to our surgical intensive care unit who were receiving mechanical ventilation. On admission, patients were randomly assigned to receive intensive insulin therapy (maintenance of blood glucose at a level between 80 and 110 mg per deciliter) or conventional treatment (infusion of insulin only if the blood glucose level exceeded 215 mg per deciliter and maintenance of glucose at a level between 180 and 200 mg per deciliter). Results At 12 months, with a total of 1548 patients enrolled, intensive insulin therapy reduced mortality during intensive care from 8.0 percent with conventional treatment to 4.6 percent (P<0.04, with adjustment for sequential analyses). The ...

https://www.nejm.org/doi/pdf/10.1056/NEJMoa011300

Intensive Insulin Therapy in Critically Ill Patients

https://www.um.es/biomybiotec/web/Seminarios/2010/papers/Cano_2.pdf

Epithelial-Mesenchymal Transitions in Development and Disease

The origins of the mesenchymal cells participating in tissue repair and pathological processes, notably tissue fibrosis, tumor invasiveness, and metastasis, are poorly understood. However, emerging evidence suggests that epithelial-mesenchymal transitions (EMTs) represent one important source of these cells. As we discuss here, processes similar to the EMTs associated with embryo implantation, embryogenesis, and organ development are appropriated and subverted by chronically inflamed tissues and neoplasias. The identification of the signaling pathways that lead to activation of EMT programs during these disease processes is providing new insights into the plasticity of cellular phenotypes and possible therapeutic interventions.

/pdf/the-basics-of-epithelial-mesenchymal-transition-xe9crzoewf.pdf

The basics of epithelial-mesenchymal transition

Increased Hospital Mortality in Patients with Bedside Hippus

Since our long-term research interest is in immune-mediated interstitial renal disease, these are the models in which we have studied the role of contrasuppression in autoimmunity. Clearly, there is no a priori reason why this should be an immunopathogenic mechanism limited to T cell-mediated tubulointerstitial disease. Indeed, early support for this kind of mechanism was previously obtained in a model of systemic autoimmunity induced by polyclonal B cell activators [25]. There are other autoimmune diseases in which Ts cells have been implicated as tolerogenic mechanisms. These include experimental type I diabets (BB rats [26] and NOD mice [8]), thyroiditis [4], oophoritis [27], and experimental allergic encephalomyelitis [28]. Contrasuppression may well be operative, at least as one process in determining susceptibility to these organ-specific autoimmune lesions. It is important to note that since the effector and regulatory T cells may belong to the same phenotypic subset, identifying a T cell subset which ‘transfers disease’ does not eliminate the possibility that regulatory cells are involved. The investigator must specifically design experiments to look for these complex interactions in order to observe them. Further elucidation of the mechanisms by which Tcs and Ts cells mediate their opposing effects will likely come from comparisons of the protein structure and receptors for their soluble factors.

Contrasuppression in autoimmunity

The capacity of the kidney to grow has been known for more than 2000 years. Aristotle (384–322 B.C.) was probably the first to describe that animals born with one kidney can develop normally, and that the single kidney is enlarged compared with the kidneys of normal two-kidney control animals (WOLF 1993). In the early nineteenth century, the French physician Pierre-Francois-Olivier Rayer (1793–1867) reported enlargement of the renal cortex in diabetes mellitus and observed that the size of the remnant kidney in patients in whom one kidney is missing approaches that of the two kidneys of healthy individuals (RAYER 1837). Rayer also undertook microscopic studies and found that “if the kidney is partially disorganized, the healthy parts become hypertrophied, resulting in a curious mixture of atrophic and hypertrophic parts” (RItz et al. 1989). Gustav Simon (1824–1876), a professor of surgery at the University of Heidelberg in Germany, performed the first unilateral nephrectomy in human subjects. The question of whether compensatory renal growth is solely an increase in protein and size (hypertrophy) or rather is caused by proliferation has puzzled students of renal growth for a long time. The famous Viennese pathologist Carl Rokitansky (1804–1878) believed that the increase in renal size after nephrectomy is true hypertrophy of all tissue constituents, whereas Simon thought that an increase in cell number was responsible for compensatory renal growth (WOlf 1993). However, most of these confusing early opinions can be attributed to the different ages of the animals used and the degree of renal ablation.

Cellular Biology of Tubulointerstitial Growth

Physician-scientists as missing persons. Association of Subspecialty Professors.

The therapeutic application of immune regulation and suppressor T cells to the control and modulation of autoimmune disease is an area of growing experimental interest. Our group has been studying experimental interstitial nephritis, both to better understand the disease process itself and to test immunoregulatory strategies for their inhibitory and protective effects. This report gives a brief overview of this work.

Eric G. Neilson

Papers

Increased Hospital Mortality in Patients with Bedside Hippus

Contrasuppression in autoimmunity

Cellular Biology of Tubulointerstitial Growth

Physician-scientists as missing persons. Association of Subspecialty Professors.

Therapeutic immune regulation in experimental interstitial nephritis with suppressor T cells and their soluble factors.