Variantes genéticas en el locus 9p21 contribuyen al desarrollo de arteriosclerosis a través de la modulación de ANRIL y CDKN2A/B

Registro creado en correspondencia al grado de doctora de Ada Congrains Castillo.Los estudios de asociación de todo el genoma (GWAS) han identificado variantes genéticas que contribuyen al riesgo de enfermedad cardiovascular (ECV) en el locus del cromosoma 9p21. La región asociada a CVD es adyacente a los dos inhibidores de quinasas dependientes de ciclina (CDKN) 2A y 2B y los últimos exones del ARN no codificante, ANRIL. Todavía no está claro cuál de estas transcripciones o cómo están involucradas en la patogénesis de la aterosclerosis.Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis.Japón. Programa de Promoción de Estudios Fundamentales en el Instituto Nacional de Innovación Biomédica de Japón (HR: 22-2-5), el Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología de Japón (KK: 22510211) y la Fundación NOVARTIS para la Investigación Gerontológica (KK).Tesi

上腸間膜動脈限局性の高安動脈炎の一例

腹痛を呈した上腸間膜動脈（superior mesenteric artery: SMA）に限局した高安動脈炎の一例を経験したので，文献的考察を加えて報告する．症例は17歳，男性．心窩部痛・右背部痛を認め，近医を受診し，その際施行した体外式腹部超音波検査（ultrasound: US）でSMA の壁肥厚が疑われ，当院総合診療科を紹介受診した．身体診察では上腹部正中に軽度圧痛を認め，血液生化学検査では血沈（60min）35mm, CRP 3.92mg/dL と軽度上昇を認めた．US では，腹痛を訴える部位に一致してSMA 起始部にびまん性の壁肥厚を認め，血管炎が疑われた．胸部造影・上腹骨盤部単純造影CT 検査（computed tomography: CT）ではSMA 周囲に造影効果を認める軟部影を認め，18F-FDGPET（18F-fluorodeoxyglucose positron emission tomography: PET）/CT 検査ではSMA 起始部付近に腫大と軽度のFDG 集積を認め，動脈炎による集積で矛盾しない所見であった．以上のことから，SMA に限局した高安動脈炎と診断した．ステロイド治療を開始し腹痛は速やかに消褪すると共に，US 所見にも改善がみられた．We report the case of a 17-year-old male who visited a hospital complaining of epigastric and right back pain. Thickening of the wall of the superior mesenteric artery （SMA) was suspected by ultrasound （US), and he was referred to our hospital. Physical examination revealed median upper abdominal tenderness. Laboratory tests showed an erythrocyte sedimentation rate （60 min) of 35 mm and C-reactive protein of 3.92mg/dL. US examination in our hospital showed diffuse wall thickening at the origin of the SMA. Because the location of the pain and the affected area identified by US were the same, we suspected angiitis. An enhanced area around the SMA was revealed by computed tomography. 18F-fluorodeoxyglucose positron emission tomography/computed tomography showed swelling at the origin of the SMA and mild accumulation of fluorodeoxyglucose. He was diagnosed with Takayasu arteritis involving the SMA. Steroid therapy was started, and his abdominal pain and US findings improved

体外式腹部超音波が診断に有用であった十二指腸巨大Brunner 腺過形成の一例

Brunner 腺過形成は十二指腸腫瘍性病変で，大きさが40mm を超えるものは10% 未満と稀である．医学中央雑誌で「腹部超音波」「Brunner 腺過形成」のキーワードで検索すると，関連した報告はない．体外式超音波検査（US）が診断に有用であったBrunner 腺過形成の一例を報告する．症例は50歳代，女性．食欲不振，心窩部痛とタール便を主訴に近医受診．貧血を認め，出血源検索目的に行った上部消化管内視鏡検査（EGD）で胃内に約 45 mm の腫瘤性病変を認め精査目的に当院紹介となった．血液生化学検査ではHb 9.1 g/dl，MCV 89.1 fl，MCH 30.0 pg と正球性正色素性貧血を認め，BUN/CRE 比は43.1と上昇していた．当院でのEGD では十二指腸球部に内腔をほぼ閉塞する45×40 mm の腫瘤性病変を認めた．腫瘤表面の異型性は目立たないが，oozing bleeding を伴ったびらん形成を認めた．粘膜下腫瘍を疑い生検も行われたが確定診断には至らなかった．単純造影CT では十二指腸球部に 45 mm 程度の腫瘤性病変を認め，辺縁は遷延性に造影された．内部は低吸収域が認められ，嚢胞変性や壊死が疑われた．周囲臓器への浸潤や転移を示唆する所見は認めず，粘膜下腫瘍が疑われたが癌は否定できなかった．US では十二指腸球部後壁の第２層から第３層に存在する約55 mm の粘膜下腫瘍が認められた．固有筋層は正常で，内部は大半が多房性嚢胞からなり，嚢胞間に充実成分がみられた．血流は比較的豊富であるが血管径や形状に明らかな不整は認めなかった．以上より十二指腸Brunner 腺過形成が疑われた．外科的切除の方針となり，開腹で十二指腸粘膜下層剥離術を行った．術材の組織診断はBrunner 腺過形成で超音波診断と矛盾しない所見であった．十二指腸粘膜下腫瘍の鑑別には超音波内視鏡が有用であるが，大きな病変では全体の描出が困難などの欠点もある．一方でUS は内視鏡侵襲なく，比較的大きな病変も描出可能で，特に本症例の様に前庭部付近は良好な観察が期待できるため，上部消化管の精査に応用できる．Brunner’s gland hyperplasia is a duodenal neoplastic lesion, and its lesions measuring >40 mm in diameter are rare, accounting for <10% of cases. A search of the Ichushi (Japana Centra Revuo Medicina) database using the keywords “abdominal ultrasound” and “Brunner’s gland hyperplasia” yielded no relevant articles. Here we report a case of Brunner’s gland hyperplasia in which transabdominal ultrasonography (US) was useful for diagnosis. A female in her 50s presented to a local hospital complaining of anorexia, epigastric pain and tarry stool. She had anemia and esophagogastroduodenoscopy (EGD), which was performed to identify the source of bleeding, revealed a mass lesion measuring approximately 45 mm in diameter in the stomach. She was referred to our hospital for further examination. Blood biochemistry showed a hemoglobin (Hb) level of 9.1 g/dL, mean corpuscular volume (MCV) of 89.1 fL and mean corpuscular hemoglobin (MCH) of 30.0 pg, indicating normocytic normochromic anemia. The blood urea nitrogen (BUN)/creatinine (CRE) ratio was as high as 43.1. In our hospital, EGD revealed a 45×40 mm mass lesion almost obstructing the lumen in the duodenal bulb. Atypia of the mass surface was not prominent, but erosion with oozing bleeding was observed. A submucosal tumor was suspected, and biopsy was performed but did not lead to a definitive diagnosis. Plain contrast-enhanced computed tomography (CT) revealed a mass lesion with prolonged peripheral enhancement measuring approximately 45 mm in diameter in the duodenal bulb. There was a low-density area inside the mass, raising the suspicion of cystic degeneration and necrosis. There were no findings suggesting infiltration or metastasis to the surrounding organs, raising the suspicion of a submucosal tumor, but cancer could not be ruled out. US revealed a submucosal tumor measuring approximately 55 mm in diameter in the second to third layer of the posterior wall of the duodenal bulb. The muscularis propria was normal and mostly composed of multilocular cysts with solid components in the space between the cysts. Blood flow was relatively abundant, but there were no obvious irregularities in the diameter or shape of blood vessels. The above findings raised the suspicion of duodenal Brunner’s gland hyperplasia. It was decided to perform surgical resection, and she underwent open duodenal submucosal dissection. Histology of the surgical specimen revealed Brunner’s gland hyperplasia, cons istent with the ultrasonographic findings. Endoscopic ultrasonography is useful in the differential diagnosis of duodenal submucosal tumors, but also has disadvantages such that it is difficult to visualize the entire lesion, when the lesion is large. On the other hand, US can be applied to the detailed examination of the upper gastrointestinal tract, because there are no invasive endoscopic procedures and US can visualize relatively large lesions and, in particular, can be expected to satisfactory observe around the vestibule, like in the present case

Variantes genéticas en el locus 9p21 contribuyen al desarrollo de arteriosclerosis a través de la modulación de ANRIL y CDKN2A/B

Registro creado en correspondencia al grado de doctora de Ada Congrains Castillo.Los estudios de asociación de todo el genoma (GWAS) han identificado variantes genéticas que contribuyen al riesgo de enfermedad cardiovascular (ECV) en el locus del cromosoma 9p21. La región asociada a CVD es adyacente a los dos inhibidores de quinasas dependientes de ciclina (CDKN) 2A y 2B y los últimos exones del ARN no codificante, ANRIL. Todavía no está claro cuál de estas transcripciones o cómo están involucradas en la patogénesis de la aterosclerosis.Genome-wide association studies (GWAS) have identified genetic variants contributing to the risk of cardiovascular disease (CVD) at the chromosome 9p21 locus. The CVD-associated region is adjacent to the two cyclin dependent kinase inhibitors (CDKN)2A and 2B and the last exons of the non-coding RNA, ANRIL. It is still not clear which of or how these transcripts are involved in the pathogenesis of atherosclerosis.Este estudio fue apoyado en parte por subvenciones en ayuda del Programa de Promoción de Estudios Fundamentales en el Instituto Nacional de Innovación Biomédica de Japón (HR: 22-2-5), el Ministerio de Educación, Cultura, Deportes, Ciencia y Tecnología de Japón (KK: 22510211) y la Fundación NOVARTIS para la Investigación Gerontológica (KK).Tesi

Relationship between atherosclerosis and occlusal support of natural teeth with mediating effect of atheroprotective nutrients: From the SONIC study

<div><p>Whereas most of studies investigating relationship between oral health and atherosclerosis have focused on periodontitis, very few of them were examined about occlusal status of natural teeth which possibly influence dietary habit. The primary aim of this cross-sectional study was to investigate the association between the occlusal support of posterior teeth and the prevalence of atherosclerosis in community-dwelling septuagenarians. Also, the second aim was to test the hypothesis that the intake of key nutrients for atherosclerosis prevention would have a mediating effect on the relationship between the occlusal status and atherosclerosis. The study population included 468 community-dwelling dentate persons aged 69–71 years recruited from the local residential registration in Japan. Participants were divided into three groups, according to the number of occlusal support zones (OSZ) in the posterior area: Complete (four OSZ), Moderate (three or two OSZ), and Collapsed (one or no OSZ). Dietary intakes were assessed using a brief-type self-administered diet history questionnaire. Atherosclerosis was defined as carotid intima-media thickness ≧1.10 mm by using carotid ultrasonography test. The logistic or linear regression model was used in multivariate analysis to assess relationship between occlusal status and atherosclerosis, and the mediating effect of key nutrients within the relationship. Multivariable analysis showed a significant association between occlusal status and atherosclerosis (odds ratio for Collapsed group to Complete group: 1.87; 95% CI: 1.45–2.41), independent of periodontal status (odds ratio: 2.01, 95%CI: 1.46–2.78). Fish and shellfish, vitamin B6 and n-3PUFAs were significantly related to both of occlusal status and atherosclerosis, and also was indicated a mediating effect on the association between occlusal status and atherosclerosis. This study implied that, within the limitation of the cross-sectional study design, the reduced posterior occlusion was related to the increased prevalence of atherosclerosis via the decline of key dietary intakes among Japanese community-dwelling dentate individuals.</p></div