An Excellent Monitoring System for Surface Ubiquitination-Induced Internalization in Mammals

Background. At present, it is difficult to visualize the internalization of surface receptors induced by ubiquitination that is taken place at the plasma membrane in mammals. This problem makes it difficult to reveal molecular basis for ubiquitinationmediated internalization in mammals. Methodology/Principle Findings. In order to overcome it, we have generated T-REx-c-MIR, a novel mammalian Tet-on B cell line using a constitutively active E3 ubiquitin ligase, c-MIR, and its artificial target molecule. By applying the surface biotinylation method to T-REx-c-MIR, we succeeded to monitor the fate of surface target molecules after initiation of ubiquitination process by doxycycline (Dox)-induced c-MIR expression. Target molecules that preexisted at the plasma membrane before induction of c-MIR expression were oligo-ubiquitinated and degraded by Dox-induced c-MIR expression. Dox-induced c-MIR expression initiated rapid internalization of surface target molecules, and blockage of the internalization induced the accumulation of the surface target molecules that were newly ubiquitinated by c-MIR. Inhibition of the surface ubiquitination by down-regulating ubiquitin conjugating enzyme E2 impaired the internalization of target molecules. Finally, a complex of c-MIR and target molecule was detected at the plasma membrane. Conclusions/ Significances. These results demonstrate that in T-REx-c-MIR, surface target molecule is ubiquitinated at the plasma membrane and followed by being internalized from the plasma membrane. Thus, T-REx-c-MIR is a useful experimental tool t

Effects of Potassium Loading and Other Stimulating Conditions on the Glomerular Zone of Fetal Adrenal Cortex of Rats

Effects of several conditions known to stimulate the zona glomerulosa of the adrenal cortex in the adult were examined on the fetal adrenal cortex of rats histochemically and electron microscopically. The stimulating conditions were the following; administration of Na restricted diet to the mother, administration of KCl or angiotensin II to the fetus, spironolactone or insulin to the mother. In these, only an intraperitoneal injection of KCl solution to the fetus affected the fetal zona glomerulosa, in which increased activity of glucose-6-phosphate dehydrogenase and hyperfunctional alteration of the mitochondria and the smooth endoplasmic reticulum were observed. This fact shows the fetal glomerulosa cells can react to orae of the specific stimuli on the adult glomerulosa cells

神経性食欲不振症に誤診された視床下部腫瘍の男性例

20歳の男性で,食欲不振,体重減少,自己嘔吐などの行動異常,病識のなさ,精神症状および人格の変化から最初の医療機関で神経性食欲不振症と誤って診断された.その後,複数の医療機関を受診したが,本人の精神および行動異常から十分な内科的検査がされず,全身状態の悪化と意識障害で当科に緊急入院した.胚細胞腫と考えられる視床下部腫瘍で,それによる下垂体機能低下症と尿崩症と診断された.患者は多飲多尿を申告せず,副腎皮質ホルモンの低下によって経過中に多尿は改善していたことが判明し,視床下部腫瘍による口渇感の喪失が明らかになった.Chipkevitchによる今まで報告された神経性食欲不振症に酷似した視床下部腫瘍21例の再検討では,やせをきたす身体疾患がないという項目以外の診断基準を完全に満たすものは2例であったが,行動および人格異常は,視床下部腫瘍による神経症状の出現に平均2.9年先行して出現しており,注意深い経過観察が必要なことを報告している.神経性食欲不振症患者数は増加しており,女子高校生や大学生の1%と推測されている.男性例も稀ではなくなり,全患者の1～5%で,当科でも1.3%である.しかし,本症の診断には器質的疾患の鑑別は非常に重要である.下垂体機能低下症と異なり,神経性食欲不振症では,血漿成長ホルモン,ACTH,コルチゾールが高値となることが多く,鑑別に有用である.A 20-year-old Japanese man with a hypothalamic tumor which caused hypopituitarism and diabetes insipidus was mistakenly diagnosed as anorexia nervosa because of anorexia, weight loss, denial of being ill, changes in personality, and abnormal behavior resembling the clinical characteristics of anorexia nervosa. After irradiation therapy, he gained weight and is behaving normally under replacement therapy. Unlike in hypopituitarism, anorexia nervosa patients often have elevated plasma levels of growth hormone (GH), cortisol or adrenocorticotropin (ACTH). Careful testing and examination must be performed to distinguish between anorexia nervosa and other organic disorders

神経性食欲不振症に誤診された視床下部腫瘍の男性例

20歳の男性で,食欲不振,体重減少,自己嘔吐などの行動異常,病識のなさ,精神症状および人格の変化から最初の医療機関で神経性食欲不振症と誤って診断された.その後,複数の医療機関を受診したが,本人の精神および行動異常から十分な内科的検査がされず,全身状態の悪化と意識障害で当科に緊急入院した.胚細胞腫と考えられる視床下部腫瘍で,それによる下垂体機能低下症と尿崩症と診断された.患者は多飲多尿を申告せず,副腎皮質ホルモンの低下によって経過中に多尿は改善していたことが判明し,視床下部腫瘍による口渇感の喪失が明らかになった.Chipkevitchによる今まで報告された神経性食欲不振症に酷似した視床下部腫瘍21例の再検討では,やせをきたす身体疾患がないという項目以外の診断基準を完全に満たすものは2例であったが,行動および人格異常は,視床下部腫瘍による神経症状の出現に平均2.9年先行して出現しており,注意深い経過観察が必要なことを報告している.神経性食欲不振症患者数は増加しており,女子高校生や大学生の1%と推測されている.男性例も稀ではなくなり,全患者の1～5%で,当科でも1.3%である.しかし,本症の診断には器質的疾患の鑑別は非常に重要である.下垂体機能低下症と異なり,神経性食欲不振症では,血漿成長ホルモン,ACTH,コルチゾールが高値となることが多く,鑑別に有用である.A 20-year-old Japanese man with a hypothalamic tumor which caused hypopituitarism and diabetes insipidus was mistakenly diagnosed as anorexia nervosa because of anorexia, weight loss, denial of being ill, changes in personality, and abnormal behavior resembling the clinical characteristics of anorexia nervosa. After irradiation therapy, he gained weight and is behaving normally under replacement therapy. Unlike in hypopituitarism, anorexia nervosa patients often have elevated plasma levels of growth hormone (GH), cortisol or adrenocorticotropin (ACTH). Careful testing and examination must be performed to distinguish between anorexia nervosa and other organic disorders