Enamel matrix derivative promotes osteoclast cell formation by RANKL production in mouse marrow cultures

OBJECTIVES: Enamel matrix derivative (EMD) is used clinically to promote periodontal tissue regeneration, however, there are few reports regarding effects of EMD on bone metabolism. We evaluated the influence of EMD on osteoclast formation using in vitro bone marrow culture. METHODS: Bioactive fractions were purified from EMD by reverse-phase HPLC on a C18 hydrophobic support, then mouse bone marrow cells were cultured with EMD or its purified fractions for 8 days. Following tartrate resistant acid phosphatase (TRAP) staining, TRAP-positive multinucleated cells were counted. The expression of receptor activator of NF-kappaB ligand (RANKL) in osteoblastic cells was detected using immunoblotting. RESULTS: EMD was dissolved in 0.1% (vol/vol) trifluoroacetic acid and applied to a C18 column for HPLC. Two major peaks were obtained of which the second (fraction numbers 21-25) was found to induce the formation of osteoclasts in mouse marrow cultures. Further, osteoprotegerin completely inhibited osteoclast formation in mouse marrow cultures with or without osteoblastic stromal cells, when being cultured with EMD or its purified fractions. In addition, Western blot analysis revealed the presence of RANKL in mouse osteoblastic cells stimulated with EMD or its purified fractions. CONCLUSION: Our results indicate that EMD induces the formation of osteoclasts through RANKL expressed by osteoblastic cells, and suggest that EMD may regulate both bone formation and bone resorption during periodontal tissue regeneration.     

Unilateral coronoid process atrophy associated with fatty degeneration of the masticatory muscles

Unilateral coronoid process atrophy associated with fatty degeneration of the masticatory muscles in a 76-year-old woman is reported. CT and plain radiogram findings are presented. The patient had no evidence of collagen disease which often causes osteolysis of the coronoid, process and condyle. Although the true cause of this deformity was unclear, a hypothesis of ischemic changes in the nutrient vessels was suggested as an etiologic factor.     

Application of neural networks to the prediction of lymph node metastasis in oral cancer

Neural networks are a new type of computing algorithm. They are especially useful in pattern recognition. In this study we applied neural networks to the prediction of lymph node metastasis of patients with oral cancer. A data set of 1,116 lymph nodes verified histopathologically was used to train and evaluate the neural networks. Various three-layer feed-forward networks with a back-propagation algorithm were employed in this study. Performance of the neural networks was compared with that of radiologists and discriminant analysis (Quantification theory type II). Neural networks had a sensitivity of 80.6% and a specificity of 94.6%. Diagnostic accuracy of the neural networks was 93.6%, which was comparable to those of discriminant analysis and clinical radiologists.     

BMP9‐ID1 signaling promotes EpCAM‐positive cancer stem cell properties in hepatocellular carcinoma

The malignant nature of hepatocellular carcinoma (HCC) is closely related to the presence of cancer stem cells (CSCs). Bone morphologic protein 9 (BMP9), a member of the transforming growth factor‐beta (TGF‐β) superfamily, was recently reported to be involved in liver diseases including cancer. We aimed to elucidate the role of BMP9 signaling in HCC‐CSC properties and to assess the therapeutic effect of BMP receptor inhibitors in HCC. We have identified that high BMP9 expression in tumor tissues or serum from patients with HCC leads to poorer outcome. BMP9 promoted CSC properties in epithelial cell adhesion molecule (EpCAM)‐positive HCC subtype via enhancing inhibitor of DNA‐binding protein 1 (ID1) expression in vitro. Additionally, ID1 knockdown significantly repressed BMP9‐promoted HCC‐CSC properties by suppressing Wnt/β‐catenin signaling. Interestingly, cells treated with BMP receptor inhibitors {"type":"entrez-nucleotide","attrs":{"text":"K02288","term_id":"191391"}}K02288 and LDN‐212854 blocked HCC‐CSC activation by inhibiting BMP9‐ID1 signaling, in contrast to cells treated with the TGF‐β receptor inhibitor galunisertib. Treatment with LDN‐212854 suppressed HCC tumor growth by repressing ID1 and EpCAM in vivo. Our study demonstrates the pivotal role of BMP9‐ID1 signaling in promoting HCC‐CSC properties and the therapeutic potential of BMP receptor inhibitors in treating EpCAM‐positive HCC. Therefore, targeting BMP9‐ID1 signaling could offer novel therapeutic options for patients with malignant HCC.     

Pathologic correlations of otologic symptoms in acute lymphocytic leukemia

Objectives

To assess the clinicopathologic correlations of otologic complaints in patients with acute lymphocytic leukemia.

Design

Otologic complaints and histologic findings were evaluated in 25 temporal bones of 13 acute lymphocytic leukemia patients.

Results

Nine patients had a history of otologic complaints, including hearing loss, otalgia, otorrhea, and vertigo in 5, 3, 3, and 2 patients, respectively. Hemorrhage was most commonly observed in the middle ear (6 patients, 9 temporal bones) and was also observed in cochlea (4 patients, 4 temporal bones), and vestibule (6 patients, 6 temporal bones). Leukemic infiltration was observed in the petrous apex (13 patients, 24 temporal bones), middle ear (7 patients, 14 temporal bones), cochlea (3 patients, 4 temporal bones), vestibule (3 patients, 4 temporal bones), and internal auditory canal (5 patients, 8 temporal bones). Inflammatory changes were observed in the cochlea (5 patients, 8 temporal bones) and vestibule (5 patients, 8 temporal bones). Middle ear effusion containing floating tumor cells was observed in 4 temporal bones of 3 patients. Irreversible histopathologic changes of the middle ear, such as the destruction of the ossicles, perforation of the tympanic membrane, and granulation tissues were observed in 5 temporal bones of 4 patients.

Conclusions

Ear involvement is common in acute lymphocytic leukemia patients. With prolonged survival due to the progress of treatment, the diagnosis and treatment of nonhematopoietic system symptoms, such as ear problems due to acute lymphocytic leukemia, have become more important.     

Clinical usefulness of a long-term treatment with an antithyroid drug for psoriasis vulgaris

We have previously reported that an antithyroid thiourethylene, thiamazole, can bring about significant clinical improvement in patients with psoriasis vulgaris. Although the efficacy of antithyroid thiourethylenes had been reported earlier, few studies have evaluated the safety of its long-term use. In this study, we aimed to study whether or not long-term thiamazole administration is complicated by any adverse effects. Eight patients with psoriasis vulgaris were enrolled in this study after informed consent was obtained. Each patient was administered thiamazole orally at 30 mg/day for 12 weeks. Two patients achieved complete clearance of psoriatic lesions. Four patients showed a significant improvement, and two patients did not reach satisfactory improvement. Some adverse effects developed in five patients; serum TSH levels elevated above the normal range in three patients and fell below the normal range in one patient. However, serum free-T3 and free-T4 levels remained within normal ranges during the treatment in all patients, and none of the patients developed clinical hypothyroidism. This preliminary study suggests that thiamazole administration is an effective and relatively safe treatment for patients with psoriasis vulgaris.