Trans-Bilayer Ion Conduction by Proline Containing Cyclic Hexapeptides and Effects of Amino Acid Substitutions on Ion Conducting Properties

Several ion channel forming cyclic peptides have been reported over the past two decades and various ion conducting mechanisms have been proposed. In this article, we report on amino acid substitutions in cyclic hexapeptides and their effects on the ion conducting properties of these peptides. Cyclic hexapeptides, cyclo(Pro-Xxx-Yyy)2, containing two Pro residues, were used as the main framework. The substitution is performed at the Xxx positions with cationic/hydrophilic Lys or hydrophobic Leu. Yyy positions were substituted with D-Phe, D-Ala, or Gly. The peptides which were absent Lys residues showed ion conducting profiles with clear transitions of electric currents, whereas the peptides containing Lys residues tended to exhibit spiky or burst-like profiles. These profiles were altered single state profiles by the protection of ε-amino groups with aromatic protecting groups. The protected analogs exhibited significant decrease in ion conductance. These results indicated that peptides containing Lys conduct ions without forming ring stacked tube-like structure. Ion channel properties were also affected by conformational changes of the cyclic peptides induced by substitution of the Yyy positions. Enhancement of intramolecular β-turn structures of cyclic peptides tended to decrease their ion conductance values

Ectopic Cervical Thymoma:A Case Report with 18F-fluorodeoxyglucose Positron Emission Tomography Findings

Ectopic thymoma is considered to arise from ectopic thymus tissue deposited as a result of the abnormal mislocalization of thymus tissue during the embryonic stage. An 86-year-old man visited our hospital with chief complaints of hoarseness and a mass in his anterior neck. A preoperative needle biopsy of the mass did not yield a definitive diagnosis. A positron emission tomography (PET) study revealed heterogeneous accumulation of 18F-fluorodeoxyglucose (FDG) in the tumor. The tumor, affecting the left sternocleidomastoid muscle, the recurrent laryngeal nerve, the internal carotid vein, and the brachiocephalic vein, was resected using a combination of a collar incision in the neck and a median incision in the sternum. Immunohistochemically, the tumor was diagnosed as an ectopic thymoma of the neck. To date, only a few cases of ectopic thymoma presenting with FDG accumulation have been reported. Our experience indicates that ectopic thymoma should be kept in mind during the differential diagnosis of neck tumors with FDG accumulation appearing on PET images

Flexural strength of the joint between glass-infiltrated alumina frames and the alumina-magnesia modifier.

PURPOSE: The purpose of the present study was to evaluate the flexural strength of the joint between glass-infiltrated alumina frames and the experimental adjusting agent (MA modifier) that contains alumina and magnesia. METHODS: A commercially available adjusting agent (Optimizer), a slurry of alumina powder (Alumina modifier), and a bulk specimen (joint-free alumina) were used as controls. Beam-shaped alumina specimens were machined from an alumina block. The ends of two alumina beams were positioned at an interval of 1.0mm and joined with each adjusting agent. The joined specimens were subjected to sintering, glass infiltration firing, glass control firing, and then a three-point bending test was carried out to evaluate the flexural strength. RESULTS: The maximum flexural strength was observed in the joint-free alumina, followed by MA modifier, Optimizer and Alumina modifier. With the exception for joint-free alumina, the failure modes after three-point bending test tended to shift from adhesive failure at substrate material-adjusting agent interface to cohesive failure within adjusting agent as the flexural strength increased. CONCLUSIONS: The use of MA modifier significantly improved the flexural strength of joined glass-infiltrated alumina frame. The MA modifier could be applied for adjusting the margin as an alternative to Optimizer when fabricating crown and bridge substructures with In-Ceram Alumina system

DNA methylation status of REIC/Dkk-3 gene in human malignancies

The REIC (reduced expression in immortalized cells)/Dkk-3 is down-regulated in various cancers and considered to be a tumor suppressor gene. REIC/Dkk-3 mRNA has two isoforms (type-a,b). REIC type-a mRNA has shown to be a major transcript in various cancer cells, and its promoter activity was much stronger than that of type-b. In this study, we examined the methylation status of REIC/Dkk-3 type-a in a broad range of human malignancies. We examined REIC/Dkk-3 type-a methylation in breast cancers, non-small-cell lung cancers, gastric cancers, colorectal cancers, and malignant pleural mesotheliomas using a quantitative combined bisulfite restriction analysis assay and bisulfate sequencing. REIC/Dkk-3 type-a and type-b expression was examined using reverse transcriptional PCR. The relationships between the methylation and clinicopathological factors were analyzed. The rate of REIC/Dkk-3 type-a methylation ranged from 26.2 to 50.0% in the various primary tumors that were examined. REIC/Dkk-3 type-a methylation in breast cancer cells was significantly heavier than that in the other cell lines that we tested. REIC/Dkk-3 type-a methylation was inversely correlated with REIC/Dkk-3 type-a expression. There was a correlation between REIC/Dkk-3 type-a and type-b mRNA expression. REIC/Dkk-3 type-a expression was restored in MDA-MB-231 cells using 5-aza-2'-deoxycytidine treatment. We found that estrogen receptor-positive breast cancers were significantly more common among the methylated group than among the non-methylated group. REIC/Dkk-3 type-a methylation was frequently detected in a broad range of cancers and appeared to play a key role in silencing REIC/Dkk-3 type-a expression in these malignancies

A case of isolated thyroid metastasis that was diagnosed 24 years after renal cancer surgery

　転移性甲状腺癌において原発部位は腎癌が最も多いとされているが，今回腎癌術後24年と長期間経過後に孤立性甲状腺転移の症例を経験したので報告する．症例は68歳，女性．既往歴に右乳癌，両側肺癌，左腎癌あり．右乳癌温存術後の放射線治療目的に前医より当院放射線治療部に紹介．位置決め CT で甲状腺右葉腫瘤を指摘され当科紹介．頸部超音波で甲状腺右葉に約３㎝大の被膜を有する低エコー腫瘤を認めた．穿刺吸引細胞診で良性との結果で経過観察としていた．その後，腫瘤の増大を認めたため，手術を勧め，甲状腺右葉切除術を行った．術後病理検査で腎癌（淡明細胞癌）の転移との診断であった．その後当院泌尿器科に紹介し，全身精査するも明らかな遠隔転移なく経過観察となっている．腎癌術後に甲状腺腫瘤を認める場合は転移の可能性を考慮する必要性があると考える．　Renal cancer is the most common primary site of metastatic thyroid cancer. We report a case of solitary thyroid metastasis 24 years after renal cancer surgery. The patient was a 68-year-old woman. She had a history of right breast cancer, bilateral lung cancer, and left kidney cancer. She was referred to our radiotherapy department by her previous doctor for radiotherapy after right breast-conserving surgery as a positioning CT scan revealed a mass in the right lobe of the thyroid gland. Cervical ultrasound showed a hypoechoic mass with a capsule about 3 cm in size in the right lobe of the thyroid gland. Puncture aspiration cytology revealed that the mass was benign, and the patient was followed up for observation. Subsequently, the mass was found to be enlarged and surgery was recommended. Right lobe thyroidectomy was performed. Postoperative pathological examination revealed metastasis of renal cancer (clear cell carcinoma). The patient was referred to the Department of Urology at our hospital for a full-body examination, but there was no obvious distant metastasis, and the patient was under observation. When a thyroid mass is found after renal cancer surgery, the possibility of metastasis should be considered

In silico structure-based drug screening of novel antimycobacterial pharmacophores by DOCK-GOLD tandem screening

Background: Enzymes responsible for cell wall development in Mycobacterium tuberculosis are considered as potential targets of anti-tuberculosis (TB) agents. Mycobacterial cyclopropane mycolic acid synthase 1 (CmaA1) is essential for mycobacterial survival because of its critical role in synthesizing mycolic acids. Materials and Methods: We screened compounds that were capable of interacting with the mycobacterial CmaA1 active site using a virtual compound library with an in silico structure-based drug screening (SBDS). Following the selection of such compounds, their antimycobacterial activity was examined. Results: With the in silico SBDS, for which we also used DOCK-GOLD programs and screening methods that utilized the structural similarity between the selected active compounds, we identified two compounds with potent inhibitory effects on mycobacterial growth. The antimycobacterial effect of the compounds was comparable to that of isoniazid, which is used as a first-line anti-TB drug. Conclusion: The compounds identified through SBDS were expected to be a novel class of anti-TB pharmacophores