ジョウチョウカンマク ドウミャクセイ ジュウニシチョウ ヘイソクショウ SMA syndrome ニ タイスル フククウキョウカ ジュウニシチョウ クウチョウ フンゴウジュツ

Superior mesenteric artery (SMA) syndrome is a rare disorder, recognized as nausea, vomiting, weight loss, and postprandial abdominal pain due to compression and obstruction of the third portion of the duodenum by the SMA. If conservative treatment fails, then duodenojejunostomy or lysis of the ligament of Treitz is indicated. Recently, laparoscopic techniques have been described. This is the first case report, to our knowledge, of performance of a laparoscopic duodenojejunostomy for treatment of SMA syndrome in Japan. A 17-year-old female with a diagnosis of SMA syndrome was prepared for surgery after having failed conservative management. Laparoscopic duodenojejunostomy was performed through the mesenterium of the transverse colon. Postoperative course was uneventful. A gastografin study obtained on postoperative day 6 demonstrated no leakage of the anastomosis and free flow of contrast medium through the duodenojejunostomy. Laparoscopic duodenojejunostomy is safe and effective and a viable method for treatment of SMA syndrome

子宮内膜症性腸閉塞に対する経肛門的イレウスチューブの有用性

One of the causative diseases of intestinal obstruction in young women is bowel endometriosis. During the course of ectopic endometriosis, it is estimated that about １０％ of patients develop bowel endometriosis. The first step in treatment is drug therapy. In cases of bowel endometriosis of the colon or rectum leading to intestinal obstruction, laparotomy is often required. A ４７-year-old woman with a history of endometriosis was undergoing drug therapy. She developed abdominal pain and nausea, and was diagnosed with septic shock and fecal ileus. A transanal drainage tube was inserted for decompression. The patient’s general condition improved, and a laparoscopic low anterior resection was performed on the ２３rd day. The patient was discharged on the １０th postoperative day without any postoperative problems. This case suggests that even in the case of septic shock caused by rectal stricture due to intestinal endometriosis, initial treatment with transanal decompression may stabilize the general condition, and may be superior in cosmetic change

A Connexin40 Mutation Associated With a Malignant Variant of Progressive Familial Heart Block Type I

Background-Progressive familial heart block type I (PFHBI) is a hereditary arrhythmia characterized by progressive conduction disturbances in the His-Purkinje system. PFHBI has been linked to genes such as SCN5A that influence cardiac excitability but not to genes that influence cell-to-cell communication. Our goal was to explore whether nucleotide substitutions in genes coding for connexin proteins would associate with clinical cases of PFHBI and if so, to establish a genotype-cell phenotype correlation for that mutation. Methods and Results-We screened 156 probands with PFHBI. In addition to 12 sodium channel mutations, we found a germ line GJA5 (connexin40 [Cx40]) mutation (Q58L) in 1 family. Heterologous expression of Cx40-Q58L in connexin-deficient neuroblastoma cells resulted in marked reduction of junctional conductance (Cx40-wild type [WT], 22.2 ± 1.7 nS, n=14; Cx40-Q58L, 0.56 ± 0.34 nS, n=14; P <0.001) and diffuse localization of immunoreactive proteins in the vicinity of the plasma membrane without formation of gap junctions. Heteromeric cotransfection of Cx40-WT and Cx40-Q58L resulted in homogenous distribution of proteins in the plasma membrane rather than in membrane plaques in ̃ 50% of cells; well-defined gap junctions were observed in other cells. Junctional conductance values correlated with the distribution of gap junction plaques. Conclusions-Mutation Cx40-Q58L impairs gap junction formation at cell-cell interfaces. This is the first demonstration of a germ line mutation in a connexin gene that associates with inherited ventricular arrhythmias and emphasizes the importance of Cx40 in normal propagation in the specialized conduction system

LPA induces keratinocyte differentiation and promotes skin barrier function through the LPAR1/LPAR5-RHO-ROCK-SRF axis

ヒト表皮細胞の分化と皮膚バリア機能の調節機構を解明 --アトピー性皮膚炎の新たな治療戦略へ向けて--. 京都大学プレスリリース. 2018-11-16.The skin barrier protects our body from water loss, allergens and pathogens. Profilaggrin (proFLG) is produced by differentiated keratinocytes and is processed into FLG monomers. These monomers crosslink keratin filaments and are also decomposed to natural moisturizing factors in the stratum corneum for skin hydration and barrier function. Deficits in FLG expression impair skin barrier function and underlie skin diseases such as dry skin and atopic dermatitis (AD). However, intrinsic factors that regulate FLG expression and their mechanism of action remain unknown. Here, we show that lysophosphatidic acid (LPA) induces FLG expression in human keratinocytes via the LPAR1 and LPAR5 receptors and the downstream RHO-ROCK-SRF pathway. Comprehensive gene profiling analysis further revealed that LPA not only induces FLG expression but also facilitates keratinocyte differentiation. Moreover, LPA treatment significantly upregulated FLG production in a three-dimensional culture model of human skin, and promoted barrier function in mouse skin in vivo. Thus, our work demonstrates a previously unsuspected role for LPA and its downstream signaling in the maintenance of skin homeostasis, which may serve as a novel therapeutic target for skin barrier dysfunction

A mouse model of 22q11.2 deletions: Molecular and behavioral signatures of Parkinson's disease and schizophrenia

神経細胞のオートファジー機能の低下と精神疾患との関連を実証 --精神疾患の新たな治療戦略の開発に期待--. 京都大学プレスリリース. 2018-09-03.Individuals with chromosome 22q11.2 deletions are at increased risk of developing psychiatric conditions, most notably, schizophrenia (SZ). Recently, clinical studies have also implicated these recurrent 22q11.2 deletions with the risk of early-onset Parkinson’s disease (PD). Thus far, the multiple mouse models generated for 22q11.2 deletions have been studied primarily in the context of congenital cardiac, neurodevelopmental, and psychotic disorders. One of these is the Df1/+ model, in which SZ-associated and developmental abnormalities have been reported. We present the first evidence that the mouse model for the 22q11.2 deletion exhibits motor coordination deficits and molecular signatures (that is, elevated α-synuclein expression) relevant to PD. Reducing the α-synuclein gene dosage in Df1/+ mice ameliorated the motor deficits. Thus, this model of the 22q11.2 deletion shows signatures of both SZ and PD at the molecular and behavioral levels. In addition, both SZ-associated and PD-relevant deficits in the model were ameliorated by treatment with a rapamycin analog, CCI-779. We now posit the utility of 22q11.2 deletion mouse models in investigating the mechanisms of SZ- and PD-associated manifestations that could shed light on possible common pathways of these neuropsychiatric disorders