Phenotypic plasticity and epithelial‐to‐mesenchymal transition in the behaviour and therapeutic response of oral squamous cell carcinoma

It is increasingly recognised that phenotypic plasticity, apparently driven by epigenetic mechanisms, plays a key role in tumour behaviour and markedly influences the important processes of therapeutic survival and metastasis. An important source of plasticity in malignancy is epithelial‐to‐mesenchymal transition (EMT), a common epigenetically controlled event that results in transition of malignant cells between different phenotypic states that confer motility and enhance survival. In this review, we discuss the importance of phenotypic plasticity and its contribution to cellular heterogeneity in oral squamous cell carcinoma with emphasis on aspects of drug resistance and EMT.     

The potential of CD44 as a diagnostic and prognostic tool in oral cancer

The CD44 family of molecules exists as a wide range of isoforms ubiquitously expressed on the surface of mammalian cells. The variation in patterns of CD44 expression on cancer cells has been widely studied in relation to their behaviour, and further interest has recently arisen in CD44 as a marker of the subfraction tumour cells acting as cancer stem cells in several types of tumours. This review focuses on the patterns of CD44 expression on the stem cell fraction of oral squamous cell carcinoma and on the relationship of detectably different patterns of CD44 expression to the behaviour of tumours.     

急性有机磷杀虫药中毒中间综合征的临床分析

目的探讨急性有机磷杀虫药中毒中间综合征（intermediate syndrome,IMS）的诊断治疗。方法回顾性分析10例IMS患者临床表现和治疗方法。结果有机磷中毒中间综合征的10例患者均出现不同程度呼吸肌麻痹症,及时建立人工气道及机械通气和乙酰胆碱酯酶（AchE）复能剂应用,治愈8例,死亡2例。结论 IMS应早期识别,建立人工气道与机械通气是抢救成功的重要方法。     

Ethanol Alters Local Cellular Levels of (3α,5α)-3-Hydroxypregnan-20-one (3α,5α-THP) Independent of the Adrenals in Subcortical Brain Regions

The neuroactive steroid (3α,5α)-3-hydroxypregnan-20-one (3α,5α-THP or allopregnanolone) is a positive modulator of GABA_A receptors synthesized in the brain, adrenal glands, and gonads. In rats, ethanol activates the hypothalamic–pituitary–adrenal axis and elevates 3α,5α-THP in plasma, cerebral cortex, and hippocampus. In vivo, these effects are dependent on both the pituitary and adrenal glands. In vitro, however, ethanol locally increases 3α,5α-THP in hippocampal slices, in the absence of adrenal influence. Therefore, it is not known whether ethanol can change local brain levels of 3α,5α-THP in vivo, independent of the adrenals. To directly address this controversy, we administered ethanol (2 g/kg) or saline to rats that underwent adrenalectomy (ADX) or received sham surgery and performed immunohistochemistry for 3α,5α-THP. In the medial prefrontal cortex (mPFC), ethanol increased 3α,5α-THP after sham surgery, compared with saline controls, with no ethanol-induced change in 3α,5α-THP following ADX. In subcortical regions, 3α,5α-THP was increased independent of adrenals in the CA1 pyramidal cell layer, dentate gyrus polymorphic layer, bed nucleus of the stria terminalis, and paraventricular nucleus of the hypothalamus. Furthermore, ethanol decreased 3α,5α-THP labeling in the nucleus accumbens shore and central nucleus of the amygdala, independent of the adrenal glands. These data indicate that ethanol dynamically regulates local 3α,5α-THP levels in several subcortical regions; however, the adrenal glands contribute to 3α,5α-THP elevations in the mPFC. Using double immunofluorescent labeling we determined that adrenal dependence of 3α,5α-THP induction by ethanol is not due to a lack of colocalization of 3α,5α-THP with the cholesterol transporters steroidogenic acute regulatory protein (StAR) or translocator protein (TSPO).     

Antibodies against Haemophilus influenzae type b in The Gambia: Investigating the extent of protection across age groups

Following a landmark clinical trial, the vaccine against Haemophilus influenzae type b (Hib) was introduced in The Gambia in 1997. Whilst the immunogenicity of this vaccine is well established subsequent to the doses administered under the EPI schedule, little data exists assessing longevity of protection, using serology. Such data are needed however to predict the susceptibility to Hib at the population level.     

Dependencies of respiratory system resistance and elastance on amplitude and frequency in the normal range of breathing

We calculated respiratory system resistance (Rrs) and elastance (Ers) from pressure and flow at the mouth in six seated subjects relaxed at FRC (cheeks tightly compressed) during sinusoidal volume forcing (250, 500, and 750 ml) at 0.2, 0.4, and 0.6 Hz. Dependencies of Rrs and Ers on frequency and tidal volume were generally the same in each subject; Rrs tended to decrease with frequency and tidal volume, whereas Ers tended to increase with frequency and decrease with tidal volume. Multiple linear regression of combined data indicated that the frequency and tidal volume effects on Rrs and Ers were significant (p less than 0.05), and that the effects on Rrs decreased at higher flows. Average Rrs was highest (4.43 cm H2O/L/s +/- 0.21 SE) at 0.2 Hz-250 ml, and lowest (3.07 cm H2O/L/s +/- 0.37) at 0.6 Hz-750 ml. Average Ers was highest (12.1 cm H2O/L +/- 1.1) at 0.6 Hz-250 ml, and lowest (7.1 cm H2O/L +/- 0.6) at 0.2 Hz-750 ml. We conclude that frequency and tidal volume dependencies in Rrs and Ers in the normal range of breathing should be considered when interpreting measurements of respiratory system impedance or developing models to describe the mechanical behavior of the respiratory system.     

Ectopic expression of rhombotin-2 causes selective expansion of CD4-CD8- lymphocytes in the thymus and T-cell tumors in transgenic mice

Although the proto-oncogene rhombotin-2 (RBTN-2) is widely expressed in most tissues, it is not expressed in T cells. We investigated the potential for overexpression of RBTN-2 to cause tumors in T cells and other tissues by constructing transgenic mice that expressed RBTN-2 under control of the metallothionein-1 promoter. Despite overexpression of RBTN-2 in all tissues, transgenic mice developed T-cell tumors only, thus indicating that tumorigenesis caused by RBTN-2 is T-cell-specific. Thymic tumors were found between 37 and 71 weeks and were invariably associated with metastasis to nonlymphoid organs. Thymuses from apparently healthy transgenic mice were also examined. In some mice there was an 10-fold increase in the CD4-CD8- thymocyte subset, yet the total number of thymocytes was the same as that in wild-type mice. Thymic homeostasis was maintained by a compensatory reduction in the CD4+CD8+ subset. The expansion of CD4-CD8- thymocytes was associated with increased expression of RBTN-2 and with increased cell proliferation. No differences were found in the proportion of thymocytes undergoing apoptosis in transgenic mice. Furthermore, RBTN-2- induced expansion of CD4-CD8- cells did not block differentiation of these cells. Thymuses with 30% CD4-CD8- cells were essentially monoclonal, indicating that all thymic immunophenotypes were derived from a single clone. Overall, our data are consistent with the following scenario: (1) RBTN-2 expression in T cells causes selective and polyclonal proliferation of CD4-CD8- thymocytes accompanied by a compensatory decrease in other thymocyte subsets; (2) a clone with growth advantage and differentiation potential is selected and populates the thymus; and (3) this clone eventually breaches homeostasis of the thymus, accompanied or followed by metastasis to other organs.