Roles of repressive epigenetic machinery in lineage decision of T cells

DNA methylation and histone modifications are central to epigenetic gene regulation, which has been shown to play a crucial role in development. Epigenetics has often been discussed in the context of the maintenance of cell identity because of the heritable nature of gene expression status. Indeed, crucial roles of the epigenetic machinery in establishment and maintenance of particular lineages during early development have been well documented. However, unexpected observation of a developmental plasticity retained in mature T lymphocytes, in particular in CD4⁺ T‐cell subsets, by recent studies is accelerating studies that focus on roles of each epigenetic pathway in cell fate decisions of T lymphocytes. Here, we focus on the repressive epigenetic machinery, i.e. DNA methylation, histone deacetylation, H3K9 methylation and Polycomb repressive complexes, and briefly review the studies examining the role of these mechanisms during T‐lymphocyte differentiation. We also discuss the current challenges faced when analysing the function of the epigenetic machinery and potential directions to overcome the problems.     

Diagnostic sensitivity of imaging modalities for hepatocellular carcinoma smaller than 2 cm

AIM:To compare the imaging results with histology and to evaluate the diagnostic sensitivity of imaging modalities for hepatocellular carcinoma(HCC)smaller than 2 cm.METHODS:Nodules smaller than 2 cm(n=34)revealed by ultrasonography(US)in 29 patients with liver cirrhosis were analyzed.Histological diagnosis of HCC was performed by ultrasonographic guidance:moderately-differentiated HCC(n=24);well-differentiated HCC(n=10).The patterns disclosed by the four imaging modalities defined the conclusive diagnosis ...     

Biochemical and genetic characterization of serologically untypable Streptococcus mutans strains isolated from patients with bacteremia

Four out of 522 streptococcal isolates from the peripheral blood of patients with bacteremia exhibited typical properties of Streptococcus mutans in terms of sucrose-dependent adhesion, expression of glucosyltransferases, fermentation profiles of sugars, the presence of surface protein antigen, and DNA-DNA hybridization. Two strains were determined as serotype f and e by immunodiffusion, whereas the other two isolates did not react with the specific antiserum to S. mutans serotype c. e. or f of the eight different serotypes of mutans streptococci. The latter two untypable isolates, however, expressed a new antigenic determinant that was different from serotype c/e/f specificity as revealed by immunodiffusion. Analysis of the cell wall polysaccharides revealed very low contents of glucose in the untypable isolates. Furthermore, Southern blot analysis demonstrated that the untypable strains lacked at least one gene corresponding to a glucose-adding enzyme. These results indicate that the serologically untypable nature is due to the loss of glucosidic residue from the serotype-specific polysaccharide antigens of S. mutans.     

Emotional stress induces transient left ventricular hypocontraction in the rat via activation of cardiac adrenoceptors: a possible animal model of 'tako-tsubo' cardiomyopathy.

The etiology of a novel cardiac syndrome 'tako-tsubo' cardiomyopathy, otherwise known as 'transient left ventricular (LV) apical ballooning' and which mimics acute myocardial infarction, is not clear; however, emotional or physical stress is known to precede the attack. Left ventriculography of rats experiencing emotional stress induced reversible LV apical ballooning, which was normalized by pretreatment with adrenoceptor blockade. Together with results of previous studies, activation of cardiac adrenoceptors in the absence of ischemia-reperfusion is proposed as the primary cause of this syndrome.     

Pathogenesis of optic-spinal MS]

We reviewed the clinical and immunological features of optic-spinal multiple sclerosis (OSMS), or relapsing neuromyelitis optica. OSMS has collected much attention as to whether it is a distinct entity from conventional MS (CMS). However, OSMS plus minor cerebral and brainstem/cerebellar involvement and the later conversion into CMS had been a diagnostic dilemma. To overcome such problems and delineate the features of OSMS, we analyzed 'Pure OSMS' with which patients had only relapsing optic neuritis and myelitis clinically and consistently normal brain MRI during 5 years or longer follow-ups. As a result, we found that this type of MS was characterized by a definite female preponderance and negative oligoclonal IgG bands (OB), although 'Pure OSMS' was heterogeneous with regards to the clinical severity and HLA class II alleles. Previously reported immunological data in OSMS include negative OB and no elevation of IL-10 or matrix metalloproteinase-9 in the cerebrospinal fluid (CSF) during relapses. In addition, we recently demonstrated that the CCR5+ Th1 cell subset in CSF during relapses, which significantly increased in CMS, remained low in OSMS. These unique clinical and immunological findings probably relate to fundamental differences in the pathogeneses of OSMS and CMS and deserve further characterization.     

Inhibitory Effect of Glucocorticoids on Human-cloned 5-hydroxytryptamine3A Receptor Expressed in Xenopus Oocytes

Background: Methylprednisolone, dexamethasone, and other glucocorticoids have been found effective against nausea and vomiting induced by chemotherapy and surgery. Although the specific 5-hydroxytriptamine3 (5-HT3) receptor antagonists such as ondansetron and ramosetron are used as antiemetics, reports show that the use of 5-HT3 receptor antagonists with some glucocorticoids brings additional effects. Glucocorticoids are reported to be antiemetic. The effect of glucocorticoids on 5-HT3 receptor, however, has not been well characterized. This study was designed to examine whether dexamethasone and methylprednisolone had direct effects on human-cloned 5-HT3A receptor expressed in Xenopus oocytes.

Methods: Homomeric human-cloned 5-HT3A receptor was expressed in Xenopus oocytes. The authors used the two-electrode voltage-clamping technique to study the effect of methylprednisolone and dexamethasone on 5-HT-induced current.

Results: Both dexamethasone and methylprednisolone concentration-dependently attenuated 5-HT-induced current. Dexamethasone inhibited 2 [mu]m 5-HT-induced current, which was equivalent to EC30 concentration for 5-HT3A receptor, with an inhibitory concentration 50% of 5.29 +/- 1.02 [mu]m. Methylprednisolone inhibited 2 [mu]m 5-HT-induced current with an inhibitory concentration 50% of 1.07 +/- 0.15 mm. The mode of inhibition with either dexamethasone or methylprednisolone was noncompetitive and voltage-independent. When administered together with the 5-HT3 receptor antagonists, ramosetron or metoclopramide, both glucocorticoids showed an additive effect on 5-HT3 receptor.