ダウン症候群児の咀嚼機能獲得に関連する要因の検討

Down syndrome (DS) has the highest prevalence of any chromosomal abnormality identified in newborns. DS children have specific eating and swallowing difficulties such as poor tongue control, mouth opening, swallowing food without chewing, and both facial and occlusal abnormalities. DS children are also at high risk of aspiration, and swallowing food without chewing is considered to be a factor associated with increased risk of aspiration and eating problems. This study aimed to identify factors preventing the acquisition of masticatory function in DS children. The subjects were 75 outpatient DS children (44 males, age range 12 to 36 month-old, mean age 33.0 ± 7.0 month­-old; 31 females, age 12 to 36 month-old, mean age 20.8 ± 8.0 month-old), who had not yet acquired masticatory function, out of 319 who visited the clinic between October 2012 and October 2017. The information necessary for assessment was retrospectively extracted from the medical records of the subjects. The items examined included age, birth weight, nutritional intake, picky eating, tactile hyperesthesia, cognitive development assessed by Ohta stage, gross motor function, occlusal condition by Hellman's dental age, and tongue thrust/lip closure/mastication while eating. The relationships between the acquisition of masticatory function and these items were investigated after one year of rehabilitation. The revealed age, low birth weight, picky eating, and gross motor function to be relevant factors. Among these, gross motor function was found to be the factor most strongly associated with acquisition of masticatory function

Centrioles: active players or passengers during mitosis?

Centrioles are cylinders made of nine microtubule (MT) triplets present in many eukaryotes. Early studies, where centrosomes were seen at the poles of the mitotic spindle led to their coining as “the organ for cell division”. However, a variety of subsequent observational and functional studies showed that centrosomes might not always be essential for mitosis. Here we review the arguments in this debate. We describe the centriole structure and its distribution in the eukaryotic tree of life and clarify its role in the organization of the centrosome and cilia, with an historical perspective. An important aspect of the debate addressed in this review is how centrioles are inherited and the role of the spindle in this process. In particular, germline inheritance of centrosomes, such as their de novo formation in parthenogenetic species, poses many interesting questions. We finish by discussing the most likely functions of centrioles and laying out new research avenues

Relationship between Gross Motor Function and Oral Parafunction Habits Relevant to Eating in Children with Down’s Syndrome

ダウン症候群患者の多くが舌突出や口唇閉鎖不全などの特有の症状を呈する．これらは保護者が発見しやすい症状であるため，摂食指導の主訴となることも多い．舌突出や口唇閉鎖不全は咀嚼や嚥下機能の阻害因子であり，長期化すると歯列や咬合状態にも影響を及ぼし，さらに摂食機能を低下させることが想定される．したがって，ダウン症候群児に特有の症状が習癖化する前にこれらの症状を改善または予防することが重要である． そこで今回，ダウン症候群児の口腔機能や摂食に関する実態を把握し，摂食指導に役立てることを目的に研究を行った． 対象は，経口摂取をしているダウン症候群児51名（男児32名，女児19名）とした．対象者の保護者から，初回の摂食指導受診日にダウン症候群児に関する質問票を記載してもらい，当日回収した．質問票の内容を検討した結果，対象者は，座位以降の粗大運動能の獲得時期が健常児より遅れる傾向にあった．対象者の約7割が摂食指導を受けた経験があったが，その指導内容の大半は食形態の指導であり，間接訓練や直接訓練の指導を受けた者は約2割であった．舌突出の有無は，年齢，歩行，筋訓練，おもちゃしゃぶりとの間に有意な関連が認められた．一方，口唇閉鎖不全の有無は，直接訓練であるかじりとり訓練との間に有意な関連が認められた．以上の結果よりダウン症候群児の舌突出と粗大運動能の発達には関連がみられ，さらに，筋訓練の導入や，一定の時期に行うおもちゃしゃぶりのようなさまざまな感覚入力が有効であることが示唆された．Children with Down’s syndrome generally have specific complications and unique development；most have some oral parafunctional habits, including mouth opening, tongue thrusting, and swallowing food without chewing. These parafunctional activities can be caused by muscle hypotonia and developmental retardation of gross motor function. However, the relationship between the development of gross motor function and oral parafunctional habits remains unclear. The purpose of the present study was to investigate the relationship between gross motor function and oral parafunctional habits in children with Down’s syndrome in order to perform effective dysphagia therapy. The subjects were children with Down’s syndrome receiving dysphagia therapy at the Tama Oral Rehabilitation Clinic at Nippon Dental University from Octber 18, 2012 to January 11, 2014. Fifty-one children（mean age 3.2 ± 1.7 years）who were able to eat orally were enrolled in the study with the consent of their parents. Parents completed a questionnaire about their child’s gross motor function and oral parafunctional habits relevant to eating at their initial clinic visit. Most children had developmental retardation of gross motor function and more than half displayed mouth opening and/or tongue thrusting. The subjects had received prior dysphagia therapy at other clinics, involving many different teaching contents. Most had received information on appropriate food choices；few had received instruction on muscle training. Tongue thrusting was significantly associated with age, development of the gross motor functions of age and walking, experience of muscle exercises, and the oral habit of sucking on toys. On the other hand, there was a significant relationship between mouth opening and biting exercises. We conclude that the development of gross motor function might be an important factor in improving oral parafunctional habits, including mouth opening and tongue thrusting for children with Down’s syndrome. Muscle exercises and sensible stimuli exercises during a specified period should be initiated as part of dysphagia therapy at an appropriate developmental stage in children with Down’s syndrome

Identification of Jumonji AT-Rich Interactive Domain 1A Inhibitors and Their Effect on Cancer Cells

Jumonji AT-rich interactive domain 1A (JARID1A), one of the jumonji C domain-containing histone demethylase (JHDM) family members, plays key roles in cancer cell proliferation and development of drug tolerance. Therefore, selective JARID1A inhibitors are potential anticancer agents. In this study, we searched for cell-active JARID1A inhibitors by screening hydroxamate compounds in our in-house library and the structural optimization based on docking study of the hit-compound to a homology model of JARID1A. As a result, we identified compound <b>6j</b>, which selectively inhibits JARID1A over three other JHDM family members. Compound <b>7j</b>, a prodrug form of compound <b>6j</b>, induced a selective increase in the level of trimethylation of histone H3 lysine 4, a substrate of JARID1A. Furthermore, compound <b>7j</b> synergistically enhanced A549 human lung cancer cell growth inhibition induced by vorinostat, a histone deacetylase inhibitor. These findings support the idea that JARID1A inhibitors have potential as anticancer agents

Basolateral Mg2+ extrusion via CNNM4 mediates transcellular Mg2+ transport across epithelia: a mouse model.

Transcellular Mg(2+) transport across epithelia, involving both apical entry and basolateral extrusion, is essential for magnesium homeostasis, but molecules involved in basolateral extrusion have not yet been identified. Here, we show that CNNM4 is the basolaterally located Mg(2+) extrusion molecule. CNNM4 is strongly expressed in intestinal epithelia and localizes to their basolateral membrane. CNNM4-knockout mice showed hypomagnesemia due to the intestinal malabsorption of magnesium, suggesting its role in Mg(2+) extrusion to the inner parts of body. Imaging analyses revealed that CNNM4 can extrude Mg(2+) by exchanging intracellular Mg(2+) with extracellular Na(+). Furthermore, CNNM4 mutations cause Jalili syndrome, characterized by recessive amelogenesis imperfecta with cone-rod dystrophy. CNNM4-knockout mice showed defective amelogenesis, and CNNM4 again localizes to the basolateral membrane of ameloblasts, the enamel-forming epithelial cells. Missense point mutations associated with the disease abolish the Mg(2+) extrusion activity. These results demonstrate the crucial importance of Mg(2+) extrusion by CNNM4 in organismal and topical regulation of magnesium