患者固有データを用いたシミュレーションモデルの構築 : 有限要素法による形態的・力学的咬合解析

内容の要旨 , 審査の要旨広島大学(Hiroshima University)博士(口腔健康科学)Philosophy in Oral Health Sciencedoctora

Phytosphingosine degradation pathway includes fatty acid alpha-oxidation reactions in the endoplasmic reticulum

Although normal fatty acids (FAs) are degraded via beta-oxidation, unusual FAs such as 2-hydroxy (2-OH) FAs and 3-methyl-branched FAs are degraded via alpha-oxidation. Phytosphingosine (PHS) is one of the long-chain bases (the sphingolipid components) and exists in specific tissues, including the epidermis and small intestine in mammals. In the degradation pathway, PHS is converted to 2-OH palmitic acid and then to pentadecanoic acid (C15:0-COOH) via FA alpha-oxidation. However, the detailed reactions and genes involved in the alpha-oxidation reactions of the PHS degradation pathway have yet to be determined. In the present study, we reveal the entire PHS degradation pathway: PHS is converted to C15: 0-COOH via six reactions [phosphorylation, cleavage, oxidation, CoA addition, cleavage (C1 removal), and oxidation], in which the last three reactions correspond to the alpha-oxidation. The aldehyde dehydrogenase ALDH3A2 catalyzes both the first and second oxidation reactions (fatty aldehydes to FAs). In Aldh3a2-deficient cells, the unmetabolized fatty aldehydes are reduced to fatty alcohols and are incorporated into ether-linked glycerolipids. We also identify HACL2 (2-hydroxyacyl-CoA lyase 2) [previous name, ILVBL; ilvB (bacterial acetolactate synthase)-like] as the major 2-OH acyl-CoA lyase involved in the cleavage (C1 removal) reaction in the FA alpha-oxidation of the PHS degradation pathway. HACL2 is localized in the endoplasmic reticulum. Thus, in addition to the already-known FA alpha-oxidation in the peroxisomes, we have revealed the existence of FA alpha-oxidation in the endoplasmic reticulum in mammals

Biological Behavior of Papillary Carcinoma of the Thyroid Including Squamous Cell Carcinoma Components and Prognosis of Patients Who Underwent Locally Curative Surgery

Thyroid carcinoma showing squamous differentiation throughout the entire lesion is diagnosed as squamous cell carcinoma of the thyroid (SCCT) in the WHO classification. This entity is a rare disease and shows a dire prognosis; however, squamous differentiation is more frequently detected in only a portion of papillary thyroid carcinoma. In this paper, we present our experience of 10 patients (8 primary lesions and 2 with recurrence in the lymph nodes) with papillary thyroid carcinoma having an SCC component (PTC-SCC). Only 3 of 8 primary lesions (38%) and none of the 2 recurrent nodes were preoperatively diagnosed as or suspected of having SCC components. All 10 patients underwent locally curative surgery. To date, 3 patients have died of carcinoma, and 2 had distant metastasis at diagnosis or had an undifferentiated carcinoma component. The other 7 are currently alive 5 to 43 months after diagnosis. Systemic adjuvant therapy after the detection of recurrence was effective for 2 patients. It is possible that some PTC-SCC patients without distant metastasis who undergo locally curative surgery can survive for a prolonged period and adjuvant therapies can be effective for local and distant recurrences

Effect of bovine milk fermented with Lactobacillus rhamnosus L8020 on periodontal disease in individuals with intellectual disability: a randomized clinical trial

Studies on the oral health of individuals with intellectual disability (ID) have identified problems that include a high prevalence of periodontal disease. The use of probiotics to treat periodontal disease has been the focus of considerable research, and bovine milk fermented with Lactobacillus rhamnosus L8020 (L8020 yogurt) has been shown to reduce the oral prevalence of four periodontal pathogens. Objective: The aim of this randomized, double-blind, placebo-controlled trial was to compare the effects of L8020 yogurt (test group) with those of placebo yogurt (placebo group) on the papillary-marginal-attached (PMA) index, gingival index (GI), and probing depth (PD) in 23 individuals with ID. Methodology: All patients were required to consume the allocated yogurt after breakfast for 90 days. PMA index and GI scores as well as PDs were assessed before the start of yogurt consumption (baseline), after 45 and 90 days of consumption, and 30 days after the cessation of consumption. Student’s t-test, Mann–Whitney U test or Fisher’s exact test was used for inter-group comparisons, and the mixed effect model of repeated measurements was used for data analysis. Results: The decrease in PMA index score was significantly greater in the test group than in the placebo group (p<0.001). The GI score also decreased during the study, with a tendency for greater decrease in the test group. Furthermore, decreases in PD between baseline, 45 and 90 days tended to be greater in the test group than in the placebo group. Conclusion: These results suggest that regular consumption of bovine milk fermented with L. rhamnosus L8020 can lower the risk of periodontal disease in individuals with ID

A preliminary study for analysis of three dimensional change of children's palates and alveolar ridges in pre-dentition period

無歯期小児における口蓋および歯槽部の経時的な形態変化を縦断採得した模型資料により立体的に分析するための基礎研究として、三次元形状計測装置を用いて、成長に伴う口蓋および歯槽部の形態変化について検討を行い、以下の結論を得た。 1)口蓋の側方および垂直方向への成長変化は生後6か月までは大きいが、その後はゆるやかであった。 2)生後7日から3か月までは側方への成長が大きく、特に生後7日から1か月にかけての成長変化が最大となった。 3)生後6か月以降は口蓋前方部の前方向への成長が大きかった。 口腔内模型を三次元形状データに変換することにより、面積や体積の計測が可能になり、数値のみならず形態変化を視覚化することが可能となった。The purpose of this study was to analyze the growth of palates and alveolar ridges in pre-dental period longitudinally and 3-dimmensionally. The study models obtained from a few volunteers during pre-dentition stage at appropriate intervals were scanned to create the corresponding 3D surface models by the use of a non-contact 3D surface scanner, and the morphological changes during growth and development periods of each individual were analyzed. 1) The palates considerably increased laterally and vertically during the first six months, and leveled off. 2) The palates increased, to a large extent, in lateral direction during first one months, and then gradually increased within 3months. 3) The size of anterior palates increased in a sagittally within the first six month. At last, the three-dimensional measuring system was useful aid to analyze the development of jaws of the nepionic children

Chronic Active Epstein–Barr Virus Infection Indistinguishable from Autoimmune Hepatitis: A Case Report

Chronic active Epstein–Barr virus (CAEBV) infection is a rare disease, mainly affecting children, typically characterized by persistent infectious mononucleosis (IM)-like symptoms. We describe an adult case of CAEBV without IM-like symptoms, which was indistinguishable from autoimmune hepatitis (AIH). A 60-year-old woman with liver damage was diagnosed with AIH (International Diagnostic Score: 16 points). She had been treated with prednisolone for three years; however, her transaminases had never normalized. She was admitted for another liver biopsy due to repeated high fevers and worsening of her liver damage over two months. Her EBV-DNA copy number was 2.9 × 104 copies/μg DNA, and EBV-encoded small RNA1-positive lymphocytic infiltration was observed in both the present and previously collected (three years ago) liver tissue samples. This case implies that hepatic involvement in a CAEBV without IM-like symptoms is difficult to distinguish from AIH and may be misdiagnosed. In some steroid resistant AIH cases, evaluating for CAEBV may be valuable

Biallelic mutations in <i>KDSR </i>disrupt ceramide synthesis and result in a spectrum of keratinization disorders associated with thrombocytopenia

Mutations in ceramide biosynthesis pathways have been implicated in a few Mendelian disorders of keratinization, although ceramides are known to have key roles in several biological processes in skin and other tissues. Using whole-exome sequencing in four probands with undiagnosed skin hyperkeratosis/ichthyosis, we identified compound heterozygosity for mutations in KDSR, encoding an enzyme in the de novo synthesis pathway of ceramides. Two individuals had hyperkeratosis confined to palms, soles, and anogenital skin, whereas the other two had more severe, generalized harlequin ichthyosis-like skin. Thrombocytopenia was present in all patients. The mutations in KDSR were associated with reduced ceramide levels in skin and impaired platelet function. KDSR enzymatic activity was variably reduced in all patients, resulting in defective acylceramide synthesis. Mutations in KDSR have recently been reported in inherited recessive forms of progressive symmetric erythrokeratoderma, but our study shows that biallelic mutations in KDSR are implicated in an extended spectrum of disorders of keratinization in which thrombocytopenia is also part of the phenotype. Mutations in KDSR cause defective ceramide biosynthesis, underscoring the importance of ceramide and sphingosine synthesis pathways in skin and platelet biology

A Cystic Lymphangioma of the Colon Seen in a Patient with Early Gastric Cancer

Lymphangiomas are very rare benign neoplasms of the gastrointestinal tract. A case of cystic lymphangioma in the hepatic flexure of the colon seen in patient with early gastric cancer is reported and the literature is reviewed

Lymphangioma of the Small Intestine : A Case Report

Lymphangiomas of the small intestine are rare tumors arising from masses of dilated lymphatic vessels in the submucosa. There are 11 cases of lymphangioma of the small intestine in the Japanese literature. We report a case of lymphangioma of the jejunum seen in a 76-year-old female and discuss with clinical feature

Rubicon and PLEKHM1 Negatively Regulate the Endocytic/Autophagic Pathway via a Novel Rab7-binding Domain

Rubicon, a subunit of the Beclin 1-PI3-kinase complex and its homologue, PLEKHM1, negatively regulate endocytic pathway through the interaction with Rab7. Synchronous association with the Beclin 1–PI3-kinase complex and Rab7 is necessary for the function of Rubicon, but not PLEKHM1