Comparisons of Clinical Features in Japanese Patients with Behçet's Uveitis Treated in the 1990s and the 2000s.

Purpose: We investigated clinical characteristics of ocular Behçet's disease (BD) patients treated in the 1990s and the 2000s.Methods: We retrospectively examined records of 68 newly arrived patients with ocular BD followed for more than 4 months during the 2000s and compared to those of 107 patients during the 1990s. Patient profiles, ocular and systemic symptoms, frequency of ocular attacks, BD ocular attack score 24-6 months (BOS24-6M), best-corrected visual acuity (BCVA), and immunomodulatory treatment were noted.Results: Clinical characteristics in the 2000s showed increases in iridocyclitis type, intestinal-, vasculo-, and neuro-BD cases, oral corticosteroid, methotrexate, and infliximab therapy usage, cataract and glaucoma surgery, and pseudophakia, and decreases in BOS24-6M and cyclophosphamide usage. BCVA of 20/30 or better at the final visit was slightly increased in the 2000s.Conclusions: Milder ocular BD tendency was seen in cases in the 2000s, whereas the incidence of special type of BD might be increasing.

TGF-ß-induced epithelial-mesenchymal transition of A549 lung adenocarcinoma cells is enhanced by pro-inflammatory cytokines derived from RAW 264.7 macrophage cells.

Cancer cells undergo epithelial-mesenchymal transition (EMT) during invasion and metastasis. Although transforming growth factor-ß (TGF-ß) and pro-inflammatory cytokines have been implicated in EMT, the underlying molecular mechanisms remain to be elucidated. Here, we studied the effects of proinflammatory cytokines derived from the mouse macrophage cell line RAW 264.7 on TGF-ß-induced EMT in A549 lung cancer cells. Co-culture and treatment with conditioned medium of RAW 264.7 cells enhanced a subset of TGF-ß-induced EMT phenotypes in A549 cells, including changes in cell morphology and induction of mesenchymal marker expression. These effects were increased by the treatment of RAW 264.7 cells with lipopolysaccharide, which also induced the expression of various proinflammatory cytokines, including TNF-α and IL-1ß. The effects of conditioned medium of RAW 264.7 cells were partially inhibited by a TNF-α neutralizing antibody. Dehydroxy methyl epoxyquinomicin, a selective inhibitor of NFκB, partially inhibited the enhancement of fibronectin expression by TGF-ß, TNF-α, and IL-1ß, but not of N-cadherin expression. Effects of other pharmacological inhibitors also suggested complex regulatory mechanisms of the TGF-ß-induced EMT phenotype by TNF-α stimulation. These findings provide direct evidence of the effects of RAW 264.7-derived TNF-α on TGF-ß-induced EMT in A549 cells, which is transduced in part by NFκB signalling.

Case of metastatic pulmonary carcinoma in optic disc diagnosed from results of biopsy performed during vitrectomy surgery.

BACKGROUND: Most intraocular metastatic tumors occur in the uveal tract, while isolated metastasis to the optic nerve is rarely found. We report a case of metastasis to the optic disc from primary lung cancer, diagnosed from biopsy findings obtained during a vitrectomy. PATIENT AND METHODS: A 69-year-old male presented with gradual visual impairment due to a milky white tumour that extended from the optic disc into the vitreous cavity. A systemic examination revealed primary squamous cell lung cancer. RESULTS: A biopsy specimen was obtained from the optic disc tumor during a vitrectomy, which led to a diagnosis of metastasis from lung cancer. Despite courses of chemotherapy and radiotherapy, the patient died of brain metastasis. DISCUSSION: There are few reports of secondary optic disc tumors and pathological biopsy findings are rare. When a milky white tumor is observed extending from the optic disc, a possible differential diagnosis is metastatic neoplasm.

c-Ski activates MyoD in the nucleus of myoblastic cells through suppression of histone deacetylases.

c-Ski, originally identified as an oncogene product, induces myogenic differentiation in nonmyogenic fibroblasts through transcriptional activation of muscle regulatory factors. Although c-Ski does not bind to DNA directly, it binds to DNA through interaction with Smad proteins and regulates signaling activities of transforming growth factor-beta (TGF-beta). In the present study, we show that c-Ski activates the myogenin promoter independently of regulation of endogenous TGF-beta signaling. Expression of myogenin is regulated by a transcription factor complex containing proteins of the MyoD family and the myocyte enhancer factor 2 (MEF2) family. c-Ski acts on the MyoD-MEF2 complex and modulates the activity of MyoD in myogenin promoter regulation. Interestingly, histone deacetylase (HDAC) inhibitors up-regulated basal activity of transcription from a MyoD-responsive reporter, although c-Ski failed to further augment this transcription in the presence of HDAC inhibitors. c-Ski is observed both in the cytoplasm and in the nucleus, but its nuclear localization is required for myogenic differentiation. We conclude that c-Ski induces myogenic differentiation through acting on MyoD and inhibiting HDAC activity in the nucleus of myogenic cells.