Regenerating islet-derived family, member 4 (Reg IV) is a candidate marker for cancer and inflammatory bowel disease. In the present study, immunohistochemical analysis of Reg IV was performed in various human neoplastic (n = 289) and non-neoplastic tissues. In the stomach, foveolar epithelium was negative for Reg IV, whereas goblet cells of intestinal metaplasia and neuroendocrine cells at the base of intestinal metaplasia expressed Reg IV. Neuroendocrine cells of the small intestine and colon showed strong expression of Reg IV, whereas goblet cells of the small intestine and colon showed weak or no expression of Reg IV. Insulin-producing beta cells of the endocrine pancreas were positive for Reg IV. Among 143 gastric adenocarcinomas, Reg IV expression was detected in 42 (29.4%) and was associated with both the intestinal mucin phenotype and neuroendocrine differentiation. No association was found between Reg IV expression and clinical characteristics such as tumour stage and patient prognosis. Of 36 colorectal adenocarcinomas, 13 (36.1%) were positive for Reg IV, which was associated with tumour stage (p = 0.0379, Fisher's exact test). Expression of Reg IV was detected in 14 (93.3%) of 15 colorectal carcinoid tumours. Reg IV expression was also detected in 5 (21.7%) of 23 ductal adenocarcinomas of the pancreas. In contrast, lung cancers (n = 30) and breast cancers (n = 30) did not express Reg IV. This is the first immunohistochemical analysis of the expression and distribution of Reg IV protein in human tumours. These data suggest that Reg IV is expressed by gastrointestinal and pancreatic tumours, including adenocarcinomas and carcinoid tumours, and that Reg IV is associated with intestinal and neuroendocrine differentiation of the stomach and gastric carcinoma.

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Posttranslational histone modifications are important for the regulation of many biological phenomena. Here, we show the purification and characterization of nucleosomal histone kinase-1 (NHK-1). NHK-1 has a high affinity for chromatin and phosphorylates a novel site, Thr 119, at the C terminus of H2A. Notably, NHK-1 specifically phosphorylates nucleosomal H2A, but not free H2A in solution. In Drosophila embryos, phosphorylated H2A Thr 119 is found in chromatin, but not in the soluble core histone pool. Immunostaining of NHK-1 revealed that it goes to chromatin during mitosis and is excluded from chromatin during S phase. Consistent with the shuttling of NHK-1 between chromatin and cytoplasm, H2A Thr 119 is phosphorylated during mitosis but not in S phase. These studies reveal that NHK-1-catalyzed phosphorylation of a conserved serine/threonine residue in H2A is a new component of the histone code that might be related to cell cycle progression.[Keywords: Nucleosome; phosphorylation; histone code; transcription; NHK-1] Supplemental material is available at http://genesdev.org.

The migration of lithium (Li) ions in electrode materials is an important factor affecting the rate performance of rechargeable Li ion batteries. We have examined Li migration in spinels LiMn(2)O(4), LiCo(2)O(4), and LiCo(1/16)Mn(15/16)O(4) by means of first-principles calculations based on density functional theory (DFT). The results showed that the trajectory of the Li jump was straight between the two adjacent Li ions for all of the three spinel compounds. However, there were significant differences in the energy profiles and the Li jump path for LiMn(2)O(4) and LiCo(2)O(4). For LiMn(2)O(4) the highest energy barrier was in the middle of the two tetrahedral sites, or in the octahedral vacancy (16c). For LiCo(2)O(4) the lowest energy was around the octahedral 16c site and the energy barrier was located at the bottleneck sites. The difference in the energy profile for LiCo(2)O(4) stemmed from the charge disproportion of Co(3.5+) to Co(3+)/Co(4+) caused by a Li vacancy forming and jumping, which was not observed for LiMn(2)O(4). Charge disproportion successfully accounted for the faster Li migration mechanism observed in LiCo(1/16)Mn(15/16)O(4). Our computational results demonstrate the importance of the effect of charge distribution on the ion jump.

ABSTRACT:There are a number of reports indicating that CYP2B6*6 (c.516G>T and c.785A>G) is responsible for decreased clearance of efavirenz (EFV), although increased disposition of cyclophosphamide (CPA) in individuals with this polymorphism was observed. Thus, we hypothesized that the effects of the two single nucleotide polymorphisms (SNPs) of CYP2B6*6 on the metabolism of drugs might be considerably different between these two agents. To clarify this possibility, we expressed two major variants of this enzyme, CYP2B6.6 (Q172H and K262R) and CYP2B6.4 (K262R), and investigated metabolic activities of these variants toward EFV and CPA. Kinetic analyses clearly indicated that CYP2B6.4 possessed enhanced metabolic activity toward EFV compared with that of the wild-type enzyme (CYP2B6.1), whereas CPA was metabolized less efficiently by CYP2B6.4 than by CYP2B6.1. On the other hand, CYP2B6.6 showed a completely opposite character, suggesting that Q172H gives inverse effects on metabolic activities of CYP2B6 affected by K262R. Although it is recognized that effects of amino acid change in cytochrome P450 on the metabolic activity depend on substrates, this study revealed SNPs giving an opposite effect on the metabolism of two clinically important drugs currently used. Furthermore, this study provides the first evidence that Q172H can reverse the direction of the effect caused by K262R in CYP2B6 on the metabolism of certain drugs.

Background and Purpose— The clinical significance of vessel wall imaging (VWI) remains unclear in patients with unruptured intracranial aneurysms. This study was performed to investigate the correlations between aneurysm wall imaging findings and histopathologic aneurysm wall architectures. Methods— A total of 9 aneurysms was evaluated by VWI and subsequently characterized with histopathology. We used VWI to visualize the aneurysm wall and determine if there was aneurysm wall enhancement after gadolinium contrast administration. Results— Aneurysm wall structures were identified in 6 of 9 unruptured intracranial aneurysms by native VWI, and wall enhancement was identified in 5 of these 6 aneurysms. Histopathologic studies revealed that wall thickening accompanied by atherosclerosis, neovascularization, and macrophage infiltration corresponded to visualization of the aneurysm wall by native VWI and to aneurysm wall enhancement. Conclusions— VWI can visualize thickening of the aneurysm wall, and wall enhancement corresponded to histologically confirmed degenerative changes accompanied by neovascularization and prominent macrophage infiltration.

Significance of alpha 9 beta 1 and alpha v beta 6 integrins expression in breast carcinoma was still unknown on clinicopathological examination. The findings of Western blot analysis may indicate that the transportation system of glycoproteins such as integrins to the cell membrane of carcinoma cells is disturbed, although these integrins can be produced.

This study demonstrated that immunohistochemistry of MUC1 is useful for the diagnosis of IMPC. The pure-IMPC cases had higher incidences of lymphatic invasion and lymph node metastasis, and also showed a poorer prognosis.