岩瀬 克己

症例は60歳,独身女性,閉経後. 1992年8月左乳房のしこりに気付き来院.腫瘤は左乳房内側上方に位置し,大きさは径約2cmで硬く,表面は凹凸不整.同側腋窩リンパ節は触れなかった.超音波検査では大きさ2.2×1.2cm,辺縁は不規則,ヤツデ状,内部は不均一な低エコー腫瘤を認めた.同時に穿刺吸引細胞診を行い,疑陽性の診断. 9月21日全麻下に腫瘤摘出生検,術中迅速組織検査を施行し,若年型線維腺腫の診断を得た.永久組織標本ではダルマ型の腫瘤のくびれた部分に大きさ2×3mmの非浸潤性小葉癌を認めた.乳腺線維腺腫は若年女性に好発し,高齢者では稀である.線維腺腫内に小葉癌を併発することがあるといわれているが,本邦における乳癌併存の報告は自験例を含め12例のみで,そのうち小葉癌が6例を占める.さらに欧米の報告を合わせても50歳以上の線維腺腫内小葉癌は極めて稀である.

Kidney function is regulated by several hormones which act through adenylate cyclasecyclic AMP system. The present study was undertaken to investigate cyclic AMP- and cyclic GMP-phosphodiesterase (cAMP-PDE and cGMP-PDE respectively) activities in the rat kidney, and also the effect of several hormones affecting the kidney function on these enzyme activities in vitro. <BR>Rat kidneys were separated into cortex and medulla. These were homogenized in 50 mM Tris-HC1 buffer, pH 7.5, containing 0.32 M sucrose and fractionated by centrifugation. PDE activity was measured in all fractions, using the two-step assay system. A low substrate concentration (0.5 μM) was used, unless otherwise stated. <BR>Substantial activity was present in all of the fractions and most of the activity existed in the soluble fraction (105000 × g supernatant). Cyclic GMP-PDE activity was dominant in both cortex and medulla. The rat kidney contained two forms of cAMP-PDE, one of which had a Km of 2.0 × 10^-4M and another which had a low Km of 2.5 × 10^-5M, and one form of cGMP-PDE with a Km of 2.5 × 10^-5M. These cAMP-PDE and cGMP-PDE were purified by Sepharose-6B column chromatography. Cyclic AMP-PDE activity was found in a broad area associated with two peaks and cGMP-PDE activity had one peak corresponding to the same peak as the hgih molecular weight cAMP-PDE. Calmodulin was eluted after the peak of cGMP-PDE activity. Both cAMP-PDE and cGMP-PDE activities were inhibited by calcium ion at a concentration of more than 5.0 × 10^-4M. Cyclic GMP-PDE activity was not activated by calmodulin in the presence of enough calcium ion.<BR>The effect of 1α, 25(OH)₂ Vit D₃, parathyroid hormone (PTH), antidiuretic hormone (ADH), calcitonin (CT), angiotensin II, and trichrolomethiazide on the partially purified cAMP-PDE and cGMP-PDE activities were examined. 1α, 25(OH)₂ Vit D₃ activated cAMP-PDE activity and did not affect cGMP-PDE activity. The concentrations of 1α, 25(OH)₂ Vit D₃ producing 50% activation of cAMP-PDE activity were 5.0 × 10^-11M (cortex) and 6.7 × 10^-10M (medulla). CT and ADH inhibited both cAMP-PDE and cGMP-PDE activities. The concentrations of CT producing 50% inhibition of cAMP-PDE activity were 4.0 ×10^-5M (cortex) and 3.3 × 10^-7M (medulla), and those of cGMP-PDE activity were 1.0 × 10^-5M (cortex) and 1.0 × 10^-4M (medulla). Concerning ADH, the concentrations required for 50% inhibition of cAMP-PDE activity were 5.3 × 10^-6M (cortex) and about 1.0 × 10^-3M (medulla), and those of cGMP-PDE activity were 5.3 × 10^-3M (cortex) and 5.3 × 10^-8M (medulla). CT inhibited cAMP-PDE activity more effectively than cGMP-PDE activity, whereas the inhibition by ADH was vice sera. PTH, angiotensin II, and trichrolomethiazide did not affect these enzyme activities. <BR>The data described here imply that these hormones may control kidney function through cyclic nucleotide metabolism by affecting cAMP-PDE and/or cGMP-PDE activity.