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

A genetic model for colorectal tumorigenesis

Because most colorectal carcinomas appear to arise from adenomas, studies of different stages of colorectal neoplasia may shed light on the genetic alterations involved in tumor progression. We looked for four genetic alterations (ras-gene mutations and allelic deletions of chromosomes 5, 17, and 18) in 172 colorectal-tumor specimens representing various stages of neoplastic development. The specimens consisted of 40 predominantly early-stage adenomas from 7 patients with familial adenomatous polyposis, 40 adenomas (19 without associated foci of carcinoma and 21 with such foci) from 33 patients without familial polyposis, and 92 carcinomas resected from 89 patients. We found that ras-gene mutations occurred in 58 percent of adenomas larger than 1 cm and in 47 percent of carcinomas. However, ras mutations were found in only 9 percent of adenomas under 1 cm in size. Sequences on chromosome 5 that are linked to the gene for familial adenomatous polyposis were not lost in adenomas from the patients with polyposis but were lost in 29 to 35 percent of adenomas and carcinomas, respectively, from other patients. A specific region of chromosome 18 was deleted frequently in carcinomas (73 percent) and in advanced adenomas (47 percent) but only occasionally in earlier-stage adenomas (11 to 13 percent). Chromosome 17p sequences were usually lost only in carcinomas (75 percent). The four molecular alterations accumulated in a fashion that paralleled the clinical progression of tumors. These results are consistent with a model of colorectal tumorigenesis in which the steps required for the development of cancer often involve the mutational activation of an oncogene coupled with the loss of several genes that normally suppress tumorigenesis.

Genetic alterations during colorectal-tumor development.

https://bic.berkeley.edu/sites/default/files/Rossi_09_TMS%20safety%20review.pdf

Safety, ethical considerations, and application guidelines for the use of transcranial magnetic stimulation in clinical practice and research

The median-effect equation derived from the mass-action law principle at equilibrium-steady state via mathematical induction and deduction for different reaction sequences and mechanisms and different types of inhibition has been shown to be the unified theory for the Michaelis-Menten equation, Hill equation, Henderson-Hasselbalch equation, and Scatchard equation. It is shown that dose and effect are interchangeable via defined parameters. This general equation for the single drug effect has been extended to the multiple drug effect equation for n drugs. These equations provide the theoretical basis for the combination index (CI)-isobologram equation that allows quantitative determination of drug interactions, where CI 1 indicate synergism, additive effect, and antagonism, respectively. Based on these algorithms, computer software has been developed to allow automated simulation of synergism and antagonism at all dose or effect levels. It displays the dose-effect curve, median-effect plot, combination index plot, isobologram, dose-reduction index plot, and polygonogram for in vitro or in vivo studies. This theoretical development, experimental design, and computerized data analysis have facilitated dose-effect analysis for single drug evaluation or carcinogen and radiation risk assessment, as well as for drug or other entity combinations in a vast field of disciplines of biomedical sciences. In this review, selected examples of applications are given, and step-by-step examples of experimental designs and real data analysis are also illustrated. The merging of the mass-action law principle with mathematical induction-deduction has been proven to be a unique and effective scientific method for general theory development. The median-effect principle and its mass-action law based computer software are gaining increased applications in biomedical sciences, from how to effectively evaluate a single compound or entity to how to beneficially use multiple drugs or modalities in combination therapies.

http://www.protocol-online.org/forums/uploads/monthly_09_2010/post-8165-008503000%201284677034.ipb

Theoretical Basis, Experimental Design, and Computerized Simulation of Synergism and Antagonism in Drug Combination Studies

Antiangiogenesis therapy has become a potentially promising tool to inhibit tumor growth by targeting an essential yet untransformed tissue component Identifying the factors involved and understanding the mechanisms required for tumor angiogenesis will facilitate efficient and specific targeting In neurofibromas, tumor growth is facilitated by a genetically and cytologically diverse mixture of cell types, including Schwann cells, fibroblast, mast cells, and neurons where nf-l-Schwann cells are most likely the tumorigenic cell type The matrix forming nf+/- cells may provide a permissive environment, facilitating tumor development, perhaps by providing landscaping factors such as the angiogenic molecules fibroblast growth factor-2, platelet-derived growth factor, endothelial growth factor, vascular endothelial growth factor, and midkine, which have been detected in neurofibromas Systemic overexpression of specific factors such as midkine owing to loss of one nf allele might further lower the overall thr

Review Article : Antiangiogenesis in Neurofibromatosis 1

Expression of L1 in primary astrocytes via a defective herpes simplex virus vector promotes neurite outgrowth and neural cell migration

✓ Nine human optic gliomas were examined in tissue culture. Typically, growth from the explants revealed well differentiated bipolar cells with abundant 9 to 10 nm fibers similar to those observed in the surgical specimens. Multinucleation was rare except for one culture, which had as many as 20 nuclei arranged in a palisading fashion along the periphery of some of the cells. Degenerative changes of the 9 to 10 nm fiber bundles with the production of amorphous electron-dense deposits were observed both in vivo and in vitro, and were thought to represent the formation of Rosenthal fibers. A distinctive feature of some of the optic gliomas was the ability of their long, thin cellular processes to form fibrous tangles in tissue culture. The correlation of these fibrous tangles in culture with Rosenthal fibers in vivo is still uncertain.

Characteristics of human optic gliomas in tissue culture

We recently reported on the extensive uncontrolled experience at Massachusetts General Hospital (MGH), Boston, suggesting the possible efficacy of cingulotomy for treating obsessive-compulsive disorder (OCD) 1 Recent evidence suggests a familial link between OCD and Tourette's syndrome (TS), 2 yet there is only one previous report regarding the effects of cingulotomy on the symptoms of TS (in two patients at MGH who underwent surgery to treat concomitant severe OCD) 3 We now report the case of a man who had concomitant OCD and TS He underwent two separate bilateral radiofrequency cingulotomies via burr holes, first in December 1989, and again in June 1991, to reduce his OCD symptoms This patient's experience is instructive because his OCD symptoms appear to have improved following these cingulotomies, while his tics were unchanged or worse Report of a Case A 35-year-old man had been followed up in our OCD clinic between 1987 and 1988

Cingulotomy in a Case of Concomitant Obsessive-Compulsive Disorder and Tourette's Syndrome

/pdf/curing-glioblastoma-oncolytic-hsv-il12-and-checkpoint-2c09gu52zb.pdf

Robert L. Martuza

Papers

Review Article : Antiangiogenesis in Neurofibromatosis 1

Expression of L1 in primary astrocytes via a defective herpes simplex virus vector promotes neurite outgrowth and neural cell migration

Characteristics of human optic gliomas in tissue culture

Cingulotomy in a Case of Concomitant Obsessive-Compulsive Disorder and Tourette's Syndrome

Curing glioblastoma: oncolytic HSV-IL12 and checkpoint blockade