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51 巻, 3 号
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土井 邦紘1975 年 51 巻 3 号 p. 129-147
発行日: 1975/03/20
公開日: 2012/09/24
ジャーナル フリーThe present study was undertaken to clarify the mechanism of the diabetogenic activity of streptozotocin. Experiments were conducted to determine the resistance of animals to the diabetogenic action of streptozotocin; to follow the time course of irreversible beta-cell damage, and to determine the influence on streptozotocin action of certain compounds.
Streptozotocin, a broad spectrum antibiotic, with antitumoral properties, was shown to be diabetogenic in rats and mice, but not in cats, rabbits, or guinea pigs.
Intravenous or intraperitoneal administration of 65 mg/kg body weight of streptozotocin to male Wistar rats evoked a tri-phasic blood sugar response. It induced an initial hyperglycemic peak with no apparent change in plasma insulin concentrations, followed by profound hypoglycemia caused by liberation of large amounts of insulin from the pancreas. Forty-eight hours after injection, the animals were completely diabetic.
Light- and electron-microscopic examinations during the first forty-eight hours after the injection of streptozotocin showed pyknosis, degranulation and marked degeneration of the beta-cells. Degenerative and necrotic changes were also seen in a few alpha-cells.
These streptozotocin-induced diabetic rats revealed polydipsia, polyuria, polyphagia and glucosuria, and decreased body weight. Blood sugar, plasma FFA and insulin concentrations were examined after oral administration of glucose (OGTT : 3 g/kg). Blood sugar and plasma FFA were significantly elevated but plasma insulin concentrations were markedly decreased, so insulin treatments were most effective in these animals.
It has been reported that nicotinamide prevents the diabetogenic activity of streptozotocin and the deformity action of 6-aminonicotinamide and 3-acetylpridine. Pretreatment with picolinamide, methyl-nicotinamide, and nicotinohydroxamic acid also blocked its diabetogenic action, but nicotinic acid, mannoheptulose and glucose were ineffective.
N-nitrosodimethylamin and ethyl-N-nitrosomethylcarbamate were devoid of diabetogenicity.
It seems that streptozotocin interfers with NAD formation in the beta-cell.
Functioning pancreatic islets cell tumors were observed on the rats both at 407 days after streptozotocin administration and at 473 days after streptozotocin administration with nicotinamide (500 mg/kg, i.p.).抄録全体を表示PDF形式でダウンロード (5274K) -
尾崎 公巳, 倉智 敬一1975 年 51 巻 3 号 p. 148-160
発行日: 1975/03/20
公開日: 2012/09/24
ジャーナル フリーAlthough many researchers have reported that RNA synthesis in the ovary is enhanced by gonadotropin treatemnt, there are only a few papers concerning the character of newly synthesized RNA after gonadotropin treatment. In this paper, the RNA synthesized in the ovary of immature rats after HCG treatment was qualitatively studied.
Immature female Sprague-Dawley rats were administered with 0.3 mc per rat of 3H-uridine at a certain time interval after injection of HCG (10 iu/rat) and the ovaries were subsequently isolated after 15, 30 or 60 minutes. RNA was extracted from the homogenate of the ovaries according to the hot phenol method after Scherrer and Darnell. The 3H-RNA thus extracted was treated with electrophoretically purified DNase to break down and remove DNA that mingled with it. The RNA solution ultimately obtained was analysed on a 3-20% sucrose gradient. The different fractions thus separated were then subjected to measurement of radioactivity and optical density at 260 mμ.
The RNA extracted from the ovary of immature untreated rat labeled with 3H-uridine for 15 minutes showed a flat pattern of radioactivity from the top to the bottom fractions with low radioactivity. Otherwise, when labeled for one hour, the RNA showed a pattern of radioactivity like those of optical density at 260 mμ with peaks of r-RNAs and t-RNA.
When the ovary was pulse-labeled with 3H-uridine for 15 minutes starting 2 hours after injection of HCG, the RNA with a large S value was synthesized and the pattern of variation in radioactivity was that of rising near the bottom fraction and declining with access to the top fraction.
The results obtained by labeling for 15 minutes starting 40 hours after PMS administration were similar to those obtained in immature untreated rats. The patterns of radioactivity in RNA obtained by the labeling for 15 minutes starting 2 hours after HCG and 42 hours after PMS were similar to those starting 2 hours after only HCG injection.
The patterns of radioactivity became similar to those of optical density at 260 mμ, when the ovaries were labeled for 30 or 60 minutes. From these results, it was suggested that the newly synthesized RNA 2 hours after HCG was constructed from m-RNA with rapid turn over and precursors of r-RNAs and t-RNA.
This RNA synthesis was blocked by pretreatment with actinomycin but not by cycloheximide. From these results, it was suggested that enhancement in RNA polymerase activity or change in template capacity of DNA which would have an effect on RNA synthesis was not based on newly synthesized protein.抄録全体を表示PDF形式でダウンロード (1073K) -
健常人および甲状腺機能異常者について大西 利夫, 宮井 潔, 熊原 雄一1975 年 51 巻 3 号 p. 161-165
発行日: 1975/03/20
公開日: 2012/09/24
ジャーナル フリーSynthetic thyrotropin-releasing hormone (TRH) has been shown to be a stimulator of prolactin release as well as of thyrotropin (TSH) release in normal man. This paper presents data concerning the effect of TRH on the PRL response in normal human subjects and in patients with thyroid diseases.
Synthetic TRH (500 μg) was administered intravenously to 12 normal males, 12 normal females, 8 female patients with hyperthyroidism, and 8 female patients with primary hypothyroidism. Blood samples were taken for the determination of the serum prolactin (PRL) and thyrotropin (TSH) concentrations.
Serum PRL and TSH levels were determined by each specific and sensitive radioimmunoassay.
The mean serum PRL level was 6.2±4.9 ng/ml (mean±SD) before TRH administration in normal females, and 4.9±5.0 ng/ml in normal males. The difference was not statistically significant. The serum PRL levels 15 min after TRH administration were significantly higher in females than in males (42.0±17.2 vs. 26.3±8.6 ng/ml, p<0.001).
The mean serum PRL level before TRH administration in patients with hyperthyroidism was higher than in normal females (12.5±5.5 vs. 6.2±4.9 ng/ml, p<0.05), but the mean serum PRL level 30 min after TRH was lower in cases of hyperthyroidism than in normal females (14.3±5.0 vs. 44.1±13.7 ng/ml, p<0.05).
The mean serum PRL level before TRH administration in primary hypothyroidism was significantly higher than in normal females (37.6±29.0 vs. 6.2±4.9 ng/ml, p<0.05) and serum PRL level after TRH was also higher in hypothyroidism than in normal females (132.8±83.4 vs. 42±17.2, p<0.05).
There was a positive correlation between the maximum increase in serum PRL concentration above the base line (ΔPRL) and the increment in serum TSH (ΔTSH) after TRH administration in these subjects.
In conclusion, the PRL response to TRH was greater in females than in males, abolished in hyperthyroidism and exaggerated in primary hypothyroidism. These results indicate that the thyroid hormone concentration influences the PRL repsonse to TRH as well as TSH response.抄録全体を表示PDF形式でダウンロード (509K) -
細木 秀美1975 年 51 巻 3 号 p. 166-181
発行日: 1975/03/20
公開日: 2012/09/24
ジャーナル フリーIn order to simplify radioimmunoassay for plasma testosterone and to measure many samples at the same time, a method of solid phase radioimmunoassay utilizing a plastic disposable microtiter tray (DMT) by which chromatography can be omitted was investigated.
Method : The antiserum was obtained by immunizing rabbits with testosterone-3 BSA which had been synthesized according to the Erlarnger's method. Plasma samples (male : 0.05 ml, female : 0.2 ml) were extracted with 1.0 ml of ether. After freezing the plasma layer in an acetone-dryice bath, the ether phase was transfered to a glass tube and evaporated to dryness. These samples and the dried standard testosterone were dissolved with borate buffer containing 3H-testosterone and transfered to plastic DMT which had been precoated with the diluted antiserum, and incubated for 24 hrs. After removal of the incubated solution, the cups of DMT were cut off and were dissolved with toluene scintillator in counting vials. The radioactivity was counted with a liquid scintillation counter.
Result : Other steroids except for 5α-dihydrotestosterone (5α-DEIT) had a low degree of cross reactivity with the antiserum. Five α-DEIT which could be measured together with testosterone in this assay was not a problem clinically because of its strong androgenic activity. The best standard curve was obtained when the antiserum was diluted to 1 : 1000. The sensitivity of this assay was 10 pg/tube. The maximal adsorption of antibody to plastic DMT was observed when the pH of antiserum was within the range of 6.5-9.5 and the precoating time was 24 hr at room temperature.
The best pH of incubation buffer was 8.0, and the antigen-antibody reaction became a plateau when the incubation exceeded 6 hrs. Water blank in this assay was 4.6±2.1 pg/tube. The recovery of testosterone (50,100,200 pg) added to 0.1 ml female plasma was 99±6.8%. Coefficients of variation within assay and between assay were below 11.2% and 20.0%, respectively. Correlation between this method and the dextran-coated charcoal method was fairly good (r=0.938). Plasma testosterone levels in 10 normal males and 12 normal females were 616±202 (mean±SD) ng/dl and 66±29 (mean ± SD) ng/dl, respectively. The levels were low in patients with hypopituitarism, hypogonadism and acromegaly. They were normal in patients with Cushing's syndrome due to adrenal hyperplasia and adenoma, but they were high in a patient with adrenal carcinoma. In a patient with testicular feminization, the level was 632 ng/dl. This increased after the administration of HCG, and decreased to 127.5 ng/dl after castration.
This solid phase radioimmnuoassay (using plastic DMT) is economically feasible as well as simple because it is possible to separate the bound hormone from the free hormone of all samples at the same time and there is little restriction in time and temperature. According to the above results, this method is suitable for routine clinical use.抄録全体を表示PDF形式でダウンロード (1602K) -
露崎 和敏, 小林 功1975 年 51 巻 3 号 p. 181-192
発行日: 1975/03/20
公開日: 2012/09/24
ジャーナル フリーIt is now postulated that prostaglandins (PG) are widely distributed in mammalian tissues and stimulate adenyl cyclase-cyclic AMP system in various organs. The present study was undertaken in an attempt to clarify the effect of PG on pituitary-thyroid axis in vivo.
Rats were maintained on a low-iodine diet for 8 days. The animals received graded doses (10-500 μg) of PGE1, PGE2 and PGF2α ip daily from day 5 to the day of autopsy. The 4-hr thyroid 131I uptake was consistently higher in 10 μg PGE1, 10 μg PGE2 and 100 μg PGF2α-treated rats than in the controls. Higher T3/T4 ratios were found in the diagested thyroids of PG-treated rats. Serum T4 levels appeared to be increased by the PG administration. However, a single injection of PG did not affect thyroid 131I uptake in iodine-deficient animals. No change in the thyroid 131I uptake was found in iodinereplete rats chronically treated with PG. The increase in plasma TSH levels during treatment with 30 μg PGE1 and PGE2 was clearly shown. A similar result was also obtained with 100 μg PGF2α.
The increase in thyroid 131I metabolism produced by the repeated administration of PG in iodine-deficient rats is due presumably to the direct stimulation on the thyroids of rats. In addition, PG elevated plasma TSH levels in such animals, probably mediated through the hypothalamic-pituitary system.抄録全体を表示PDF形式でダウンロード (1385K)
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