Growth inhibition of multiple myeloma cells by a novel IkappaB kinase inhibitor.

Involvement of nuclear factor-kappaB (NF-kappaB) in cell survival and proliferation of multiple myeloma has been well established. In this study we observed that NF-kappaB is constitutively activated in all human myeloma cell lines, thus confirming the previous studies. In addition, we found the phosphorylation of p65 subunit of NF-kappaB in addition to the phosphorylation of IkappaBalpha and the activation of NF-kappaB DNA binding and that various target genes of NF-kappaB including bcl-x(L), XIAP, c-IAP1, cyclin D1, and IL-6 are up-regulated. We then examined the effect of a novel IkappaB kinase inhibitor, 2-amino-6-[2-(cyclopropylmethoxy)-6-hydroxyphenyl]-4-piperidin-4-yl nicotinonitrile (ACHP). When myeloma cells were treated with ACHP, the cell growth was efficiently inhibited with IC(50) values ranging from 18 to 35 mumol/L concomitantly with inhibition of the phosphorylation of IkappaBalpha/p65 and NF-kappaB DNA-binding, down-regulation of the NF-kappaB target genes, and induction of apoptosis. In addition, we observed the treatment of ACHP augmented the cytotoxic effects of vincristine and melphalan (l-phenylalanine mustard), conventional antimyeloma drugs. These findings indicate that IkappaB kinase inhibitors such as ACHP can sensitize myeloma cells to the cytotoxic effects of chemotherapeutic agents by blocking the antiapoptotic nature of myeloma cells endowed by the constitutive activation of NF-kappaB.     

Concurrent deletion of BMP4 and OTX2 genes,two master genes in ophthalmogenesis

BMP4 and OTX2 are master genes in ophthalmogenesis. Mutations of BMP4 and OTX2 often lead to eye defects, including anophthalmia–microphthalmia. A significant degree of variable expressivity has been reported in heterozygous individuals with BMP4 or OTX2 mutation. Interestingly, both BMP4 and OTX2 reside on 14q22, being only 2.8 Mb apart. Previous studies reported that among three patients with 14q22 deletion involving BMP4 and OTX2, all had severe eye defects. The minimal degree of variable expressivity among these individuals who were doubly deleted for BMP4 and OTX2 could be attributed to the combinatorial relationship of the two genes observed in animal models. We herein report a patient with a concurrent deletion of BMP4 and OTX2 who exhibited bilateral microphthalmia, more specifically, anterior segment dysgenesis with microcornea. Evolutionarily conserved physical linkage of Bmp4 and Otx2 loci may suggest an advantage of the proximal alignment of the two genes. Another striking feature in the propositus was the progressive white matter loss observed by serial neuroimaging. A review of twelve previously reported patients with 14q22 microdeletion revealed decreased white matter volume in half of the patients. It remains to be elucidated whether the white matter lesion is age-dependent and progressive. In conclusion, anterior segment defects of the eyes, especially when accompanied by decreased white matter volume on neuroimaging, should raise the clinical suspicion of 14q22 microdeletion.     

Bonding performance and interfacial characteristics of short fiber‐reinforced resin composite in comparison with other composite restoratives

The purpose of this study was to investigate the shear bond strength (SBS) and surface free‐energy (SFE) of short fiber‐reinforced resin composite (SFRC), using different adhesive systems, in comparison with other composite restoratives. The resin composites used were everX Posterior (EP), Clearfil AP‐X (CA), and Filtek Supreme Ultra Universal Restorative (FS). The adhesive systems used were Scotchbond Multi‐Purpose (SM), Clearfil SE Bond (CS), and G‐Premio Bond (GB). Resin composite was bonded to dentin, and SBS was determined after 24 h of storage in distilled water and after 10,000 thermal cycles (TCs). The SFEs of the resin composites and the adhesives were determined by measuring the contact angles of three test liquids. The SFE values and SFE characteristics were not influenced by the type of resin composite, but were influenced by the type of adhesive system. The results of this study suggest that the bonding performance and interfacial characteristics of SFRC are the same as for other composite restoratives, but that these parameters are affected by the type of adhesive system. The bonding performance of SFRC was enhanced by thermal cycling in a manner similar to that for other composite restoratives.     

Posterior cerebral artery dissection on a serial magnetic resonance angiography

Posterior cerebral artery (PCA) dissection in children seldom is reported in the literature. This is the second report of acute PCA dissection with infarct occurring in a young child. A serial magnetic resonance angiography demonstrated a delayed and transient narrowing of the arterial caliber, which was consistent with a focal PCA dissection with delayed vascular recanalization. PCA dissection should be included in the causes of infarct in children and a thorough and serial neurovascular imaging should be considered if no cause of stroke is found.     

Shear fatigue strength of resin composite bonded to dentin at physiological frequency

The purpose of this study was to examine the shear fatigue strengths of a resin composite bonded to dentin. Three adhesive systems – a two‐step self‐etch adhesive (OptiBond XTR; Kerr) and two universal adhesives [Scotchbond Universal (3M ESPE) and G‐Premio Bond (GC)] – were used in self‐etch mode to bond a resin composite to dentin at a physiologic frequency of 2 Hz over 50,000, 100,000, and 1,000,000 cycles. A staircase method of fatigue testing was used. Twenty specimens were used for each test condition. There was no significant difference in shear fatigue strength across the cycling periods for the three individual adhesives. Differences in shear fatigue strength were found among the three adhesives within each cycling period. Regardless of the adhesive used in self‐etch mode for bonding a resin composite to dentin, shear fatigue strength was not influenced by the number of cycles used for testing.     

Treatment outcome of laparoscopic surgery after self-expandable metallic stent insertion for obstructive colorectal cancer

International Journal of Clinical Oncology - We assessed the technical and oncological safety of self-expandable metallic stent (SEMS) insertion followed by laparoscopic colorectal surgery as a...     

Effect of a functional monomer (MDP) on the enamel bond durability of single‐step self‐etch adhesives

The present study aimed to determine the effect of the functional monomer, 10‐methacryloxydecyl dihydrogen phosphate (MDP), on the enamel bond durability of single‐step self‐etch adhesives through integrating fatigue testing and long‐term water storage. An MDP‐containing self‐etch adhesive, Clearfil Bond SE ONE (SE), and an experimental adhesive, MDP‐free (MF), which comprised the same ingredients as SE apart from MDP, were used. Shear bond strength (SBS) and shear fatigue strength (SFS) were measured with or without phosphoric acid pre‐etching. The specimens were stored in distilled water for 24 h, 6 months, or 1 yr. Although similar SBS and SFS values were obtained for SE with pre‐etching and for MF after 24 h of storage in distilled water, SE with pre‐etching showed higher SBS and SFS values than MF after storage in water for 6 months or 1 yr. Regardless of the pre‐etching procedure, SE showed higher SBS and SFS values after 6 months of storage in distilled water than after 24 h or 1 yr. To conclude, MDP might play an important role in enhancing not only bond strength but also bond durability with respect to repeated subcritical loading after long‐term water storage.