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

http://ggdpathway.wustl.edu/files/2014/08/ACMG-Guidelines-2015_Richards-et-al.pdf

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

BACKGROUND Most patients with non-small-cell lung cancer have no response to the tyrosine kinase inhibitor gefitinib, which targets the epidermal growth factor receptor (EGFR). However, about 10 percent of patients have a rapid and often dramatic clinical response. The molecular mechanisms underlying sensitivity to gefitinib are unknown. METHODS We searched for mutations in the EGFR gene in primary tumors from patients with non-small-cell lung cancer who had a response to gefitinib, those who did not have a response, and those who had not been exposed to gefitinib. The functional consequences of identified mutations were evaluated after the mutant proteins were expressed in cultured cells. RESULTS Somatic mutations were identified in the tyrosine kinase domain of the EGFR gene in eight of nine patients with gefitinib-responsive lung cancer, as compared with none of the seven patients with no response (P<0.001). Mutations were either small, in-frame deletions or amino acid substitutions clustered around the ATP-binding pocket of the tyrosine kinase domain. Similar mutations were detected in tumors from 2 of 25 patients with primary non-small-cell lung cancer who had not been exposed to gefitinib (8 percent). All mutations were heterozygous, and identical mutations were observed in multiple patients, suggesting an additive specific gain of function. In vitro, EGFR mutants demonstrated enhanced tyrosine kinase activity in response to epidermal growth factor and increased sensitivity to inhibition by gefitinib. CONCLUSIONS A subgroup of patients with non-small-cell lung cancer have specific mutations in the EGFR gene, which correlate with clinical responsiveness to the tyrosine kinase inhibitor gefitinib. These mutations lead to increased growth factor signaling and confer susceptibility to the inhibitor. Screening for such mutations in lung cancers may identify patients who will have a response to gefitinib.

/pdf/activating-mutations-in-the-epidermal-growth-factor-receptor-4a7r2t8eq0.pdf

Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib

Receptor tyrosine kinase genes were sequenced in nonsmall cell lung cancer (NSCLC) and matched normal tissue. Somatic mutations of the epidermal growth factor receptor gene EGFR were found in 15 of 58 unselected tumors from Japan and 1 of 61 from the United States. Treatment with the EGFR kinase inhibitor gefitinib (Iressa) causes tumor regression in some patients with NSCLC, more frequently in Japan. EGFR mutations were found in additional lung cancer samples from U.S. patients who responded to gefitinib therapy and in a lung adenocarcinoma cell line that was hypersensitive to growth inhibition by gefitinib, but not in gefitinibinsensitive tumors or cell lines. These results suggest that EGFR mutations may predict sensitivity to gefitinib. Protein kinase activation by somatic mutation or

https://science.sciencemag.org/content/sci/early/2004/04/29/science.1099314.full.pdf

EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy.

Phenomenological electronic energy bands in graphite intercalation compounds

AIM: To examine the association of Epstein-Barr virus (EBV) with carcinoma of the ear. METHODS: Five non-keratinising squamous cell carcinomas and two undifferentiated carcinomas of the ear were examined. In situ hybridisation was used to localised EBV-encoded RNAs (EBER). Immunohistochemical methods to detect LMP-1 and EBNA2 were performed in the EBER positive cases. RESULTS: Two cases were EBER positive, including one non-keratinising and one undifferentiated carcinoma. Both showed identical morphology to those arising from the nasopharynx, with abundant lymphoid stroma. They were both negative for LMP-1 and EBNA2. CONCLUSIONS: EBV associated carcinoma with the morphology of lymphoepithelioma can also arise from the middle ear.

https://jcp.bmj.com/content/jclinpath/51/8/602.full.pdf

Presence of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the middle ear.

A phenomenological model based on staging periodicity and in-plane superlattice symmetry is developed for the electronic dispersion relations for graphite intercalation compounds. The formalism is applicable to arbitrary stage and intercalant, and is tractable for high-stage compounds where the first-principles calculations are prohibitively complex. In-plane and ${k}_{z}$-axis zone folding of the three-dimensional graphite effective-mass Hamiltonian forms the basis for studying the effect of the intercalant on the graphite host. To calculate energy bands for a stage-$n$ compound, matrix elements for every ($n+1$) st graphite layer are replaced by those for intercalate layers in the Hamiltonian. The minimum number of parameters is used as required by symmetry. Specific application indicates that the transport properties and Fermi-surface topology can be explained approximately on the basis of our model using pristine-graphite parameters. A single additional parameter ${\ensuremath{\mu}}_{0}$ is introduced to account for the shift in potential of the graphite bounding layer, the shift being related to charge transfer to or from the graphite. Additional intercalate-graphite and intercalate-intercalate interaction parameters can serve to fine tune the electronic dispersion relations and to obtain intercalate-dependent properties. The model provides a very simple mathematical form for the calculation of optical properties, Landau-level quantization, and Fermi-surface topology.

Dispersion relations in graphite intercalation compounds: Electronic energy bands

We report a Chinese patient who presented with metastatic undifferentiated carcinoma in the cervical lymph node of unknown primary origin. Despite a raised IgA titre against Epstein-Barr virus capsid antigen, examination and biopsy of the nasopharynx were negative. Radiotherapy was given to the head and neck region with the orbit shielded. There was complete resolution of the metastatic lymph nodes. She developed proptosis of her left eye one year afterward when a large tumour was found in the lacrimal sac region. Review of the initial computerized tomography revealed a small soft tissue mass in the same region. The tumour was composed of undifferentiated carcinoma cells associated with dense lymphoid infiltrate. In situ hybridization for Epstein-Barr virus EBER RNA showed strong positive signals in the malignant cells. This is the first reported case of an Epstein-Barr virus positive undifferentiated carcinoma with lymphoid stroma in the lacrimal sac. In addition to the nasopharynx, salivary glands, nasal cavity and paranasal sinuses, the lacrimal sac should be considered as a potential primary site for Epstein-Barr virus positive metastatic undifferentiated carcinoma in the cervical lymph nodes.

Suet Yi Leung

Papers

Phenomenological electronic energy bands in graphite intercalation compounds

Presence of Epstein-Barr virus in lymphoepithelioma-like carcinoma of the middle ear.

Dispersion relations in graphite intercalation compounds: Electronic energy bands

An Epstein-Barr virus positive undifferentiated carcinoma in the lacrimal sac

Ecotoxicological study on sediments of Mai Po marshes, Hong Kong using organisms and biomarkers