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70 巻, 8 号
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齋藤 史郎, 高橋 秀夫1994 年 70 巻 8 号 p. 907-912
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーThe application of the microdialysis technique for the analysis of neuropeptide release was described. The recoveries of neuropeptides are affected by the nature of the dialysis membrane, the sort of perfusion method, the internal diameter and length of the outlet tube, and the flow rate of the perfusate. The studies on the mechanism of neuropeptide release using brain microdialysis were summarized. Brain microdialysis technique allows the direct and dynamic analysis of neuropeptide release and provides a useful tool for studying the mechanism of the central regulation of the release of neuropeptides.抄録全体を表示PDF形式でダウンロード (714K) -
太田 昌宏, 湊 宏一, 星野 敏也, 平林 尚之, 本間 誠次郎1994 年 70 巻 8 号 p. 913-924
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーWe studied the adrenosuppressive effect of antiandrogen TZP-4238 and its metabolites. The binding affinity for the corticosteroid receptor using rat hepatic cytosol was in the order 11-OH TZP-4238>11, 15-(OH)2TZP-4238>>TZP-4238?15-OH TZP-4238>11-keto TZP-4238.
Male beagle dogs aged 1-6 years were randomly divided into TZP-4238 (0.05, 0.5mg/kg) treatment groups and CMA (0.5mg/kg) treatment group. Each group was administered the drug per os every day for 8 weeks. Plasma cortisol, TZP-4238 and its metabolite levels were measured by on-line coupling of liquid chromatography with thermospray or atmospheric pressure ionization mass spectrometry using selective ion monitoring (LC-MS/SIM). LC-MS/SIM provided a sensitive and reliable method of unequivocal confirmation of the presence of steroidal drugs in the plasma. The plasma cortisol level was lowered below 1ng/ml at 1 week after oral administration of TZP-4238 at 0.5mg/kg or CMA at 0.5mg/kg. The decline continued throughout the treatment for 8 weeks. Upon termination of administration, the cortisol level returned to the normal level (6ng/ml) by 4 weeks. However in the group given 0.05mg/kg TZP-4238, the cortisol level remained within the normal range. To analyze the cortisol decreasing mechanism, we administered TZP-4238 at 0.5mg/kg for 7 days to one beagle dog. When the plasma 11-OH TZP-4238 level was increased, the cortisol level decreased time dependently and the concentration of plasma 11-OH TZP-4238 which induced 50% inhibition was 2ng/ml. The decrease in the plasma cortisol level was highly correlated to the extent of the increase of the plasma 11-OH TZP-4238 (r2=0.840).
We conclude that the adrenosuppresive effect of antiandrogen TZP-4238 is not due to TZP-4238 itself but its metabolite 11-OH TZP-4238.抄録全体を表示PDF形式でダウンロード (1070K) -
本間 誠次郎, 鈴木 和浩, 竹沢 豊, 湊 宏一, 深堀 能立, 山中 英寿1994 年 70 巻 8 号 p. 925-940
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーTZP-4238, a new steroidal antiandrogen, is an orally active drug in rats and dogs. The effects of TZP-4238 on the androgen receptor and androgen content were examined in comparison with other antiandrogens in rats
The prostate DHT levels decreased markedly within 4-8 hr after a single oral administration of TZP-4238 8mg/kg. The prostatic testosterone concentrations fell below the detection limit (5pg/g of tissue) at 4-12 hr after the initiation of treatment. The plasma testosterone level also fell to 60% of the control level after 4-8 hr and then returned to the normal range. Eighty percent of DHT present in normal prostatic tissue was located in the nuclear fraction. TZP-4238 reduced the concentration of DHT in nuclei to 50% of the normal level. The concentration of the plasma drug which induced a 50% decrease in the prostatic DHT, the IC50, was about 10ng/ml, while the IC50 value for plasma testosterone was 30-50ng/ml. After oral administration of 15-OH TZP-4238, the main metabolite, the level of plasma testosterone was significantly elevated above the control level. The androgen receptor level was markedly reduced at 24 hr following castration and returned to the normal range within 5 hr of a single injection of testosterone. TZP-4238 reduced the nuclear androgen receptor level to 60% at 24 hr after a single oral dose and then, the receptor content returned to its original level. Both 15-OH TZP-4238 and cyproterone acetate also reduced the androgen receptor and DHT contents to 50%. A series of in vivo studies demonstrated that TZP-4238 inhibited the uptake of testosterone and the decrease of DHT and testosterone, and decreased the nuclear androgen receptor in the rat prostate.抄録全体を表示PDF形式でダウンロード (1407K) -
五味渕 大平1994 年 70 巻 8 号 p. 941-950
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーAdrenal tumors showing no clinical manifestations (incidentaloma) are frequently encountered during imaging analysis upon routine examinations. These tumors are sometiomes associated with hypertension and/or diabetes mellitus (DM). We have examined six cases of incidentalomas with these symptoms in this study. All patients underwent endocrinological evaluation by measuning plasma cortisol and aldosterone levels to assess adrenocortical function. The levels of urinary 17-hydroxysteroids, 17-ketosteroids and catecholamines were also measured. Imaging analysis were performed by using 131I-adosterol scintigraphy, computed tomography and magnetic reconance imaging. Whereas one case was diagnosed as having an adrenal adenoma without the examination of a surgical specimen, other cases underwent surgical removal of the tumor, and final diagnoses were made by pathohistological examination of the tumors.
Three cases were diagnosed as having adrenocortical adenomas (one was functioning and others were non-functioning) and one case was diagnossed as having a functional adrenocortical carcinoma. Adenomas were found to produce either non-functional steroids or a small amount of functional steroid hormones. The adenoma patients all suffered hypertension, whereas one of the adenoma patients and the carcinoma patient showed signs of DM. By contrast, of the six cases, one case was diagnosed as having an adrenal cyst, and one case was diagnosed with myelolipoma. Although these two cases suffered DM and hypertension, respectively, it seemed to be unlikely that these clinical symptoms were caused by the adrenal disease. Thus, the present analysis of the six incidentaloma patients suggests that once an adrenal incidentaloma patient with hypertension and/or DM is found, both endocrinological and imaging examinations are necessary to determine the indication of surgical treatment. This analysis supports the present consensus that non-functional adenomas whose sizes are 3cm or less and whose sizes do not change at any reevaluation period, as well as adrenal cysts and myelolipoma should not be surgically removed.抄録全体を表示PDF形式でダウンロード (1179K) -
癌関連遺伝子の発現に関する免疫組織化学的検討渋谷 雄平, 井上 大輔, 須川 秀夫, 森 徹1994 年 70 巻 8 号 p. 951-956
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーA case with primary triple cancers including thyroid cancer is reported.
A 57-year old woman complaining of laryngeal discomfort was found to have an firm elastic lump on the right anterior neck. On 123I scan, the nodule in the right thyroid lobe accumulated considerable amounts of radioiodine as a warm nodule, while the remainder of the gland showed decreased uptake. Thyroid hormone levels remained within normal ranges. Cytological findings obtained by fine-needle aspiration biopsy showed papillary carcinoma. Right lobectomy was performed. The histological examinations revealed papillary carcinoma embedded within adenomatous thyroid tissue. It is probable that the surrounding adenomatous tissue accumulated radioiodine, since the warm nodule on 123I scan was larger than the size of the carcinoma. Examinations of the gastrointestinal tract revealed the presence of poorly differentiated adenocarcinoma in the stomach and well differentiated adenocarcinoma (carcinoma in adenoma) in the rectum. Expressions of ras p21 and p53 were examined immunohistochemically in these carcinoma tissues. The ras p21 product was clearly detected in not only the thyroid carcinoma but in a part of the surrounding adenomatous regions as well. Both ras p21 and p53 proteins were observed in the rectal cancer tissue. In contrast, these oncoproteins were not found in the gastric cancer tissue. In this case ras oncogene activation may be an early event in the tumorigenic process of the thyroid and rectum. However, different genetic alterations seem to occur during the development of these three carcinomas.抄録全体を表示PDF形式でダウンロード (3574K) -
石突 吉持, 広岡 良文, 谷川 俊一, 澤井 喜邦1994 年 70 巻 8 号 p. 957-966
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーWe have carried out a follow-up study on iodine-induced goiter to clarify whether or not iodine could be a factor in the progression as well as the promotion of thyroid autoimmunity.
We selected 143 women of child-bearing age without any previous thyroid disorders who had received hysterosalpingography (H. S. G.). 45 Sex and age-matched healthy subjects were chosen as controls.
Serum nonhormonal iodine (S. N. I.) levels, frequency of goiter and antimicrosomal antibody (MCHA) in all the Lipiodol-cases were significantly higher than those in the controls (p<0.001, <0.01 and <0.01), respectively. When the subjects were divided into 9 groups according to the duration of each 5 months after H. S. G., serum TSH and S. N. I. levels, incidence of goiter and MCHA in the initial group were significantly higher than those in the other groups (p<0.05). The S. N. I. levels became normalized in 30 months after H. S. G. and the goiters disappeared in almost the same duration, while the incidence of higher MCHA titers declined gradually but significantly around 40 months after H. S. G. compared with that in the first 5 months after H. S. G.(p<0.05). The frequency of goiter and MCHA in 44 cases after a 6-39 month follow-up decreased significantly compared to that in the initial group (p<0.05). Therefore, we tried an individual longitudinal follow-up study on MCHA titer in 12 cases for 35-103 months, resulting in a significant reduction or negativeness of the titer in 6 cases. Likewise, MCHA titers in all cases decreased significantly (p<0.05) on later evaluation.
The present data suggest that iodine in Lipiodol administered via the vagina will act not only as the promoting factor, but as an aggravating agent for thyroid autoimmunity.抄録全体を表示PDF形式でダウンロード (936K) -
村上 剛1994 年 70 巻 8 号 p. 967-978
発行日: 1994/10/20
公開日: 2012/09/24
ジャーナル フリーNitric oxide (NO), a simple gas with free radical chemical properties, is synthesized by nitric oxide synthase (NOS) from arginine in neurons and acts as a neurotransmitter in the central and peripheral nervous systems. The immunohistochemical demonstration of NOS-immunoreactivity and its histochemical marker, NADPH-diaphorase activity in many neurons of the hypothalamus, suggest that NO plays a role in controlling the production and/or release of hypothalamic neuroendocrine peptides. In the present study, the expression of NOS in the enkephalin and dynorphin systems of the rat hypothalamus was examined by the combined method of the NADPH-diaphorase histochemistry and the immunocytochemistry of methionine enkephalin (M-Enk) or dynorphin B (Dyn-B). About 6 to 9% of M-Enk immunoreactive neurons in the paraventricular, arcuate and ventromedial nuclei expressed NADPH-diaphorase activity. Dyn-B immunoreactive neurons, however, showed NADPH-diaphorase activity in high ratio (37%-84%) in the supraoptic nucleus and the parvocellular and magnocellular paraventricular nucleus. These results revealed that a part of the enkephalin and dynorphin neurons in the rat hypothalamus have the ability to produce NO. The high ratio of expression of NO in magnocellular neurosecretory dynorphin containing neurons suggested that NO participates in controlling posterior pituitary hormone secretion together with dynorphin.抄録全体を表示PDF形式でダウンロード (2555K)
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