日本内分泌学会雑誌
Online ISSN : 2186-506X
Print ISSN : 0029-0661
ISSN-L : 0029-0661
66 巻, 3 号
選択された号の論文の7件中1~7を表示しています
  • -細胞傷害性T細胞によるNODマウス膵ラ島β細胞破壊機構-
    馬場 茂明, 永田 正男
    1990 年 66 巻 3 号 p. 145-158
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    Proliferation of islet-associated leukocytes occurred when isolated islets from 20 week-old female Non-obese Diabetic (NOD) mice were cultured with 10U/ml recombinant interleukin-2 (rIL-2) for 7 days. Co-culture of these lymphocytes with freshly-isolated islets from 6-8 week-old NOD donors in the presence of 1U/ml rIL-2 produced islet structural deformation within 24h and islet cytolysis within 48h. Three lines of evidence suggest that leukocytes were cytotoxic T lymphocytes (CTL) specific for islet cells. First, these proliferating cells adhered to NOD islets at 6h and specifically killed islets after 48h of culture, but the cytoadherence of these cells to the other organs including thyroid, pancreatic exocrine glands and liver from NOD mice could not be observed and the shape of tissue clumps hardly deformed after culture for 48h. The accumulated insulin release from NOD islets to the medium after 6h of culture was significantly increased in the presence of islet-derived cells compared with the insulin release in the absence of cells. On the contrary, lactic dehydrogenase activity released from liver and amylase activity from pancreatic exocrine glands showed on difference between with and without these cells for 6h of culture. Second, a flow cytometric analysis showed that these cells consisted of 96%Thy1.2, 70%Lyt2, and 8%L3T4-positive cells. After treatment with monoclonal anti-Thy1.2 or Lyt2 antibody and complement, these cells lost their activity to destroy NOD islets. However, these cells still had a full killing activity after the depletion of L3T4-positive cells. Third, islets of NOD (H-2genotype KdDb), B10.GD (H-2KdDb), BALB/cA (H-2d), and DBA/2N (H-2d) were susceptible to destructive activity of these cells, whereas islets of NON (H-2b), C57BL/6N (H-2b), C57BL/10J (H-2b), and C3H/He (H-2k) mice remained intact. Furthermore, anti-Kd monoclonal antibody could prevent islet-specific cytolysis of these cells.
    These results suggest that CTL expressing Thy1.2 and Lyt2 phenotypes appear to recognize islet cell antigen with restriction of major histocompatibility complex (MHC) class H-2Kd and then destroy pancreatic β cells in NOD mice.
  • 塚本 卓治
    1990 年 66 巻 3 号 p. 159-167
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    The basic properties of estradiol 2-hydroxylase in rat brain microsomes were studied and compared to the known characteristics of rat liver microsomal estradiol 2-hydroxylase.
    Rat liver microsomal estradiol 2-hydroxylase, which has been considered to be a cytochrome P450-like enzyme, was largely inhibited by carbon monoxide. On the other hand, the effect of carbon monoxide on the activity of rat brain microsomal estradiol 2-hydroxylase was rather weak. A known inhibitor of cytochrome P450, SKF-525A inhibited rat liver microsomal estradiol 2-hydroxylase in a concentration-dependent manner. The concentration of SKF-525A causing 50% inhibition of liver microsomal estradiol 2-hydroxylase was 33μM where the substrate concentration was 1μM. Conversely, the inhibitory effect of SKF-525A on the activity of brain microsomal estradiol 2-hydroxylase was much less. Moreover, norepinephrine inhibited brain microsomal estradiol 2-hydroxylase in a competitive manner, however, the effect of physiological concentrations of norepinephrine on liver microsomal estradiol 2-hydroxylase was negligible.
    These results suggest that the nature of microsomal estradiol 2-hydroxylase in rat brain is quite different from that of liver microsomal estradiol 2-hydroxylase.
  • 村松 弘章, 鈴木 義信, 土屋 時彦, 大武 龍介, 橋上 好久, 小堀 博文, 堀越 健太郎, 鈴木 仁, 下田 新一
    1990 年 66 巻 3 号 p. 168-174
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    In order to assess a possible involvement of thyroid hormone in atrial natriuretic peptide (ANP), experimentally induced hyper- and hypothyroid rats were employed, and the immunoreactive rat ANP (IR-ANP) concentrations in plasma, atria and brain regions including the hypothalamus were measured by a specific radioimmunoassay. Plasma IR-ANP concentration in hypothyroid rats was 14.5±2.9 (mean ± SEM) fmol/ml, significantly lower than that in control rats (p<0.05 vs control of 24.9±9.7 fmol/ml). Plasma IR-ANP concentration in hyperthyroid rats was 66.4±9.7 fmol/min, significantly higher than that in the controls (p<0.01). Atrial IR-ANP concentration in hyperthyroid rats was significantly lower than that in the controls (79.9±11.1 nmol/g vs 133.5±21.2 nmol/g (control), p<0.05), though no significant change was observed in atrial IR-ANP concentration in hypothyroid rats.
    While hypothalamic ANP concentration in hypothyroid rats was significantly lower than that in the controls (17.5±3.5 pmol/g vs 31.9±1.9 pmol/g (control), p<0.05), there was no significant change of that in the hyperthyroid rats. On reverse phase high performance liquid chromatography, the major peak in plasma and hypothalamus extract was thought to be identical to synthetic α-rat ANP (1-28). These results may suggest that in the hyperthyroid state an excessive amount of ANP is released from atria into the blood, and that in the central nervous system thyroid hormone involve ANP metabolism being different from the atrium.
  • 森 昭裕, 山北 宜由, 伊藤 康文, 安田 圭吾, 三浦 清
    1990 年 66 巻 3 号 p. 175-181
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    We report a 17 year old patient with mixed gonadal dysgenesis (MGD) raised as a female. The patient had undergone amputation of the phallus at 10 months of age and showed short and masculinized characteristics with ambiguous external genitalia.Abdominal exploration revealed a hypoplastic uterus with a fallopian tube and streak gonad on the right side and a poorly developed testis and epididymis with was deferens on the left side. Following chromosomal analysis, the cultured peripheral lymphocytes and bone marrow cells showed 45,X in karyotype. Although the mosaicism of 45,X/46,X+ mar was revealed by both G- and Q- banding methods in the cultured skin fibroblasts and the cells of various gonadal organs examined, the rate of 45,X karyotype was high (77-97%) in the cells of each organ tissue. Endocrine examinations showed plasma testosterone levels to be slightly higher than those of a normal female. The response of plasma testosterone and estradiol to HCG was low. Hypergonadotropic hypogonadism was revealed.
  • 吉村 學, 西村 眞人
    1990 年 66 巻 3 号 p. 182-197
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    It has been widely revealed that an insulin-like immunoreactive substance (ILI) is distributed in the brain, particularly in the hypothalamus and circumventricular areas where it is supposed that the balances of water and electrolytes are regulated. Although the insulin synthesis of the brain has not been clarified, the existence of ILI in the brain is clearly demonstrated, and ILI may play some important physiological roles on blood pressure regulation as well as feeding behavior.
    Taking notice of the Na+-K+ ATPase activating action of insulin, we aimed to investigate the central cardiovascular effects of insulin using rats, in comparison with the endogenous digoxin-like immunoreactive substance (DLI), which exists in the same sites of ILI, inhibits Na+-K+ ATPase activity, and increases blood pressure.
    When rats were fed high-salt diets for 4 weeks, hypothalamic and pituitary contents of ILI decreased significantly compared to those of rats on a regular diet. Intracerebro-ventricular (i. c. v.) infusion of insulin lowered the femoral arterial pressure and decreased the heart rate significantly in both urethane-anesthetized and conscious rats, and inhibited the renal sympathetic activities in urethane-anesthetized rats. Intravenous infusion of the same amounts of insulin, however, influenced neither blood pressure nor heart rate. Simultaneous i. c. v. infusion of insulin abolished the elevation of both blood pressure and heart rate produced by i. c. v. infusion of hypertonic saline. The increase in the plasma DLI was also abolished significantly. Inhibiting central sympathetic nerve activities and DLI secretion from the hypothalamus, cerebral insulin may effect the central regulations of blood pressure, particularly in salt-loading conditions.
  • 安西 正, 小峰 仙一
    1990 年 66 巻 3 号 p. 198-206
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    Mammary gland lipase activity of the mouse increased 45-fold compared to that in unmated gland at the 15th day of pregnancy and was 65-fold at the 20th day of pregnancy.After parturition, the activity abruptly decreased during 3 days to 38% of that at the 20th day of pregnancy. On the other hand, only a very small lipoprotein lipase activity was observed in the pregnant gland, the activity increased to 15-fold that of 20 day pregnancy at the 3rd day of lactation. These facts suggest that the mammary epithelial cells (mammary gland lipase activity was detected only in epithelial cells) utilize the fat reserved in the gland during pregnancy, but the lactating mammary epithelial cells utilize the fat supplied from the blood circulation.
    Mammary gland lipase activity was decreased by treatment with epinephrine which increased the fat mobilization in other adipose tissues. Hydrocortisone and prolactin decreased the mammary gland lipase activity in the glands of pregnancy and lactation. In addition, no hormone-sensitive lipase activity was observed in the mammary gland. Thus, the control of fat mobilization in the mammary gland must be different from that in other adipose tissues.
  • 長谷川 眞, 飯野 史郎, 伊藤 國彦, 浜田 昇
    1990 年 66 巻 3 号 p. 207-217
    発行日: 1990/03/20
    公開日: 2012/09/24
    ジャーナル フリー
    In order to discover whether or not thyroid function in patients with Hashimoto's disease will move toward hypothyroidism with age, we investigated the thyroid function and antithyroid antibody titers at the initial examination and 5 years later in 181 patients with goitrous Hashimoto's thyroiditis. Pregnant patients and those within 1 year of the postpartum period were excluded. The thyroid function was assessed before medication or at least one month after stopping it. At the initial examination, 52% (94 cases) of the cases were euthyroid, 24% (44 cases) were subclinically hypothyroid and 24% (43 cases) were hypothyroid. It was not observed whether the incidence of hypothyroidism tended to be greater in older patients or in patients with longer duration of illness. Five years later, 68% of euthyroid patients at the initial examination remained in euthyroid state, 18% had become subclinically hypothyroid, and 9% were hypothyroid. The thyroid function was not evaluated in 5% of the patients because they were under treatment with 1-thyroxine. In the patients with subclinical hypothyroidism at the initial examination, 30% had become euthyroid, 23% remained subclinically hypothyroid, 32% had become hypothyroid and 16% were not evaluated. Thirty percent of the patients with hypothyroidism at the initial examination had become euthyroid, 7% were subclinically hypothyroid, 28% remained hypothyroid and 35% were not evaluated. The higher the titer of TGHA, the higher the percentage of hypothyroidism at the first examination. A similar but much stronger tendency was observed in the patients with a higher titer of MCHA. In the patients with a higher titer of TGHA, the number of hypothyroid patients approximately doubled after 5 years, although such a tendency was not observed in the patients with a higher titer of MCHA. In patients with persistent hypothyroidism, the age was significantly higher, the serum concentration of T3 lower and the titer of TGHA at the initial examination and MCHA 5 years later higher than in the patients with transient hypothyroidism. The titer of MCHA was significantly decreased 5 years later in patients with transient hypothyroidism.
    From these results, it is indicated that in patients with goitrous hypothyroidism, the incidence of hypothyroidism was higher in the cases with high titers of antithyroid antibody than in those with low titers, and that in the patients with transient hypothyroidism, the age was lower, the serum level of T3 higher and the titer of TGHA lower than in the cases with permanent hypothyroidism. It was concluded that the thyroid function in Hashimoto's thyroiditis does not consistently move toward the hypothyroid range, but it sometimes recovers even from the hypothyroid state, and that there are certain close relations between the thyroid function and the titers of TGHA and MCHA, although they are similar but quite different from one another.
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