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.

Although the existence of three different cDNA forms of human GTP cyclohydrolase I (GCH I) have been reported (Togari et al., 1992), the full-length sequence of any human GCH I cDNA involving poly (A) tail has not yet been documented. In the present study, we first isolated a full-length cDNA clone encoding human GCH I type 1 from human pheochromocytoma cDNA library. The length of the cDNA insert was 2,921 base pairs including poly (A) tail. RNA blot analysis showed a single mRNA species of 4.0 kb in human pheochromocytoma tissue.

The intracellular localization of tyrosine hydroxylase (TH), which is the rate limiting enzyme in catecholamine (CA) biosynthesis, and its activity in various adrenal and other neuroendocrine tumors was studied. TH was strongly localized in adrenal medulla, pheochromocytoma, and paraganglioma, but was scatteredly expressed in neuroblastoma. TH was not detected in adrenocortical tumors, ganglioneuroma, and other neuroendocrine tumors. Neuron specific enolase (NSE) was found in all neuroendocrine tumors, but Grimelius staining showed only the secreting granules of the tumor cells. TH activity was significantly high in pheochromocytoma and paraganglioma as compared with that in normal adrenal gland, whereas TH activity was low in a neuroblastoma and was undetectable in other tumors. These findings indicate that TH correlates well with the biosynthetic function of CA in the tumor cell and, thus, both the immunostaining of TH and the measurement of its activity in adreno-medullary and related tumors may provide some information about the process of cell differentiation in these tumors.

The activity of DNA polymerase beta (beta-enzyme) in bovine and rat pituitary glands was remarkably higher in the anterior than in the posterior lobe. In sucrose gradient centrifugation, the activity in the anterior lobe of the bovine pituitary gland appeared at the sedimentation constant, 3.3 S, while that of rat pituitary gland appeared at 3.3 S, 7.3 S and 12 S, respectively. The activity in each fraction increased in the anterior lobes of rat pituitaries that were stimulated to release TSH by decreased thyroid hormone levels induced by an antithyroid drug. These results suggest that the activity of the beta-enzyme is high in the cells of the anterior lobe which are hyperfunctioned to produce pituitary thyreotrophic hormone and may be controlled by hormonal feedback regulation.

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.