Brain Metastasis from Gastrointestinal Stromal Tumor: A Case Report and Review of the Literature

Metastasis of gastrointestinal stromal tumor (GIST) into the central nervous system is extremely rare. We report a patient with synchronous GIST and brain metastasis. At disease onset, there was left hemiplegia and ptosis of the right eyelids. Resection cytology of the brain tumor was reported as metastasis of GIST. After positron emission tomography examination, another tumor in the small bowel was discovered, which suggested a small bowel GIST associated with intracranial metastasis. Immunohistochemical analysis of the intestinal tumor specimen obtained by double balloon endoscopy showed a pattern similar to the brain tumor, with the tumors subsequently identified as intracranial metastases of jejunal GIST. After surgical resection of one brain tumor, the patient underwent whole brain radiation therapy followed by treatment with imatinib mesylate (Gleevec; Novartis Pharma, Basel, Switzerland). Mutational analysis of the original intestinal tumor revealed there were no gene alterations in KIT or PDGFRα. Since the results indicated the treatment had no apparent effect on either of the tumors, and because ileus developed due to an intestinal primary tumor, the patient underwent surgical resection of the intestinal lesion. However, the patient's condition gradually worsen and she subsequently died 4 months after the initial treatment

Cell-to-Cell Transformation in Escherichia coli: A Novel Type of Natural Transformation Involving Cell-Derived DNA and a Putative Promoting Pheromone

Escherichia coli is not assumed to be naturally transformable. However, several recent reports have shown that E. coli can express modest genetic competence in certain conditions that may arise in its environment. We have shown previously that spontaneous lateral transfer of non-conjugative plasmids occurs in a colony biofilm of mixed E. coli strains (a set of a donor strain harbouring a plasmid and a plasmid-free recipient strain). In this study, with high-frequency combinations of strains and a plasmid, we constructed the same lateral plasmid transfer system in liquid culture. Using this system, we demonstrated that this lateral plasmid transfer was DNase-sensitive, indicating that it is a kind of transformation in which DNase-accessible extracellular naked DNA is essential. However, this transformation did not occur with purified plasmid DNA and required a direct supply of plasmid from co-existing donor cells. Based on this feature, we have termed this transformation type as ‘cell-to-cell transformation’. Analyses using medium conditioned with the high-frequency strain revealed that this strain released a certain factor(s) that promoted cell-to-cell transformation and arrested growth of the other strains. This factor is heat-labile and protease-sensitive, and its roughly estimated molecular mass was between ∼9 kDa and ∼30 kDa, indicating that it is a polypeptide factor. Interestingly, this factor was effective even when the conditioned medium was diluted 10–5–10–6, suggesting that it acts like a pheromone with high bioactivity. Based on these results, we propose that cell-to-cell transformation is a novel natural transformation mechanism in E. coli that requires cell-derived DNA and is promoted by a peptide pheromone. This is the first evidence that suggests the existence of a peptide pheromone-regulated transformation mechanism in E. coli and in Gram-negative bacteria

Reliability and validity of the patient disability-oriented diagnostic nomenclature system for prosthetic dentistry

Purpose: The Japan Prosthodontic Society (JPS) has proposed a new diagnostic nomenclature system (DNS), based on pathogenesis and etiology, to facilitate and improve prosthodontic treatment. This systemspecifies patient disability and the causative factor (i.e. ‘‘B (disability) caused by A (causative factor)’’). The purpose of this study was to examine the reliability and validity of this DNS. Study selection: The JPS Clinical Guideline Committee assessed mock patient charts and formulated disease names using the new DNS. Fifty validators, comprising prosthodontic specialists and dental residents, made diagnoses using the same patient charts. Reliability was evaluated as the consistency of the disease names among the validators, and validity was evaluated using the concordance rate of the disease names with the reference disease names. Results: Krippendorff’s α was 0.378 among all validators, 0.370 among prosthodontic specialists, and 0.401 among dental hospital residents. Krippendorff’s α for 10 validators (3 specialists and 7 residents) with higher concordance rates was 0.524. Two validators (1 specialist and 1 resident) with the highest concordance rates had a Krippendorff’s α of 0.648. Common disease names had higher concordance rates, while uncommon disease names showed lower concordance rates. These rates did not show correlation with clinical experience of the validator or time taken to devise the disease name. Conclusions: High reliability was not found among all validators; however, validators with higher concordance rates showed better reliability. Furthermore, common disease names had higher concordance rates. These findings indicate that the new DNS for prosthodontic dentistry exhibits clinically acceptable reliability and validity

Medical Treatment of Postendoscopic Submucosal Dissection Phlegmonous Gastritis in an Elderly Diabetic Woman with Myelodysplastic Syndrome

Phlegmonous gastritis is a rare, suppurative disease characterized by full-thickness exudative changes, infiltration of inflammatory cells, and edema primarily in the submucosal layer. A 76-year-old woman with type 2 diabetes and myelodysplastic syndrome underwent endoscopic submucosal dissection (ESD) for early gastric cancer. Postoperatively, she developed persistent fever and computed tomography displayed full-circumference thickening of the gastric wall and increased levels of fat stranding. Endoscopy showed post-ESD ulcer floor expansion, formation of a false lumen between the ulcer floor and surrounding folds, and adhesion of purulent matter. Klebsiella pneumoniae, Pseudomonas aeruginosa, and Candida albicans were detected from pus culture and Klebsiella pneumoniae from blood culture, leading to a diagnosis of phlegmonous gastritis. Contrast examination showed no leakage outside the gastric wall; therefore, the patient fasted and was given antibiotics. She was successfully treated with medical therapy, as demonstrated by repeat endoscopy. Based on our experience, we recommend antibiotics before and after ESD in patients thought to be at high risk of infection, as well as careful postoperative management including postoperative endoscopy

Inhibitory Effects of Small-Molecule CCR5 Antagonists on Human Immunodeficiency Virus Type 1 Envelope-Mediated Membrane Fusion and Viral Replication

We established a human immunodeficiency virus type 1 (HIV-1) envelope (Env)-mediated membrane fusion assay and examined the small-molecule CCR5 antagonist TAK-779 and its derivatives for their inhibitory effects on HIV-1 Env-mediated membrane fusion and viral replication. The membrane fusion assay is based on HIV-1 long terminal repeat-directed β-d-galactosidase reporter gene expression in CD4- and CCR5-expressed HeLa (MAGI-CCR5) cells after cocultivation with effector 293T cells expressing HIV-1 Env. Inhibition of HIV-1 replication was also determined in MAGI-CCR5 cells infected with the corresponding cell-free HIV-1. TAK-779 effectively suppressed R5 HIV-1 (strain JR-FL) Env-mediated membrane fusion as well as viral replication. Its 50% inhibitory concentrations (IC(50)s) for membrane fusion and viral replication were 0.87 ± 0.11 and 1.4 ± 0.1 nM, respectively. These values corresponded well to the IC(50) for (125)I-RANTES (regulated on activation, T cell expressed, and secreted) binding to CCR5 (1.4 nM). The inhibitory effects of 18 TAK-779 derivatives on membrane fusion differed from one compound to another. However, there was a close correlation among their inhibitory effects on membrane fusion, viral replication, and RANTES binding. The correlation coefficient between their IC(50)s for membrane fusion and viral replication was 0.881. Furthermore, since this assay depends on Env expressed in the effector cells, it is also applicable to the evaluation of CXCR4 antagonists. These results indicate that the HIV-1 Env-mediated membrane fusion assay is a useful tool for the evaluation of entry inhibitors

Porphyromonas gingivalis-derived lysine gingipain enhances osteoclast differentiation induced by tumor necrosis factor-\alpha and interleukin-1\beta but suppresses that by interleukin-17A : importance of proteolytic degradation of osteoprotegerin by lysine gingipain

Periodontitis is a chronic inflammatory disease accompanied by alveolar bone resorption by osteoclasts. Porphyromonas gingivalis, an etiological agent for periodontitis, produces cysteine proteases called gingipains, which are classified based on their cleavage site specificity (i.e. arginine (Rgps) and lysine (Kgps) gingipains). We previously reported that Kgp degraded osteoprotegerin (OPG), an osteoclastogenesis inhibitory factor secreted by osteoblasts, and enhanced osteoclastogenesis induced by various Toll-like receptor (TLR) ligands (Yasuhara, R., Miyamoto, Y., Takami, M., Imamura, T., Potempa, J., Yoshimura, K., and Kamijo, R. (2009) Lysine-specific gingipain promotes lipopolysaccharide- and active-vitamin D(3)-induced osteoclast differentiation by degrading osteoprotegerin. Biochem. J. 419, 159–166). Osteoclastogenesis is induced not only by TLR ligands but also by proinflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, and IL-17A, in inflammatory conditions, such as periodontitis. Although Kgp augmented osteoclastogenesis induced by TNF-α and IL-1β in co-cultures of mouse osteoblasts and bone marrow cells, it suppressed that induced by IL-17A. In a comparison of proteolytic degradation of these cytokines by Kgp in a cell-free system with that of OPG, TNF-α and IL-1β were less susceptible, whereas IL-17A and OPG were equally susceptible to degradation by Kgp. These results indicate that the enhancing effect of Kgp on cytokine-induced osteoclastogenesis is dependent on the difference in degradation efficiency between each cytokine and OPG. In addition, elucidation of the N-terminal amino acid sequences of OPG fragments revealed that Kgp primarily cleaved OPG in its death domain homologous region, which might prevent dimer formation of OPG required for inhibition of receptor activator of nuclear factor κB ligand. Collectively, our results suggest that degradation of OPG by Kgp is a crucial event in the development of osteoclastogenesis and bone loss in periodontitis