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67 巻, 10 号
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森 昭裕, 梶田 和男, 山北 宜由, 森田 浩之, 村井 敏博, 安田 圭吾, 杉浦 正彦, 三浦 清1991 年 67 巻 10 号 p. 1147-1161
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーRecently several types of anti-pituitary-antibodies (APA) have been found in patients with pituitary disorders including hypopituitarism and diabetes incipidus, and in postpartum women. However, the pathophysiological role(s) of APA still remains unknown. In order to elucidate the clinical significance of APA, longitudinal follow-up and family study of APA in patients with hypopituitarism were performed.
APA in serum was examined in a total of 11 patients with various types of hypopituitarism (7 of isolated ACTH deficiency, 1 of partial hypopituitarism, 3 of Sheehan's syndrome, 6 males and 5 females). Chronic thyroiditis was associated in 3 out of 7 patients with isolated ACTH deficiency, and empty sella was found in each one patient with isolated ACTH deficiency and partial hypopituitarism, and in 3 patients with Sheehan's syndrome. APA was examined on 2 or 3 occasions at more than a 6 month interval (longitudinal study). In 5 patients, their 16 family members were examined for the presence of APA, and pituitary functions were evaluated in 3 out of 7 family members with positive APA (family study). For pituitary function tests, arginine infusion test, TRH, LH-RH or CRH test and insulin tolerance test were performed. APA reacting to rat pituitary cytoplasmic antigens (pituitary cell antibodies: PCA) and APA reacting to rat GH3 cells and/or mouse AtT20 cells surface antigens (pituitary cell surface antibodies: PCSA) were assayed with indirect immunofluorescence method.
At the initial examination, 6 out of 11 patients (55%) showed positive APA. Thepatients were divided into 3 subgroups according to the longitudinal study: the group with disappearance of initially positive APA (3 patients), the group with altered titers or types of initially positive APA (3 patients), and the group with sustained initially negative APA (4 patients). No effects of replacement therapy on the alterations of APA were observed.
In 16 family members of 5 patients (each 1 with partial hypopituitarism and isolated ACTH deficiency syndrome, and 3 with Sheehan's syndrome), APA in their sera were investigated. Seven out of 16 members (44%) showed positive APA. Among 6 first-degree relatives of 16 family members, both or either one of APA and PCSA were positive in 4 (67%). Out of 10 of their second- or third-degree relatives, 3 (30%) were positive for PCA or PCSA. All of 3 relatives with positive APA studied showed mild pituitary hypofunction without any clinical manifestations.
These results suggest the possibility that autoimmune mechanism-induced hypofunction as well as hereditary background might participate in the pathogenesis of some hypopituitarism, and that APA might have a causative role in such disorders.抄録全体を表示PDF形式でダウンロード (1993K) -
高田 幸伸, 板東 浩, 宮本 貴由, 小阪 昌明, 佐野 寿昭1991 年 67 巻 10 号 p. 1162-1177
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーThe effect of growth hormone (GH) on immune function was studied using normal and hypophysectomised male Wistar rats. Hypophysectomy was performed by the auditory approach at 4 weeks of age. Normal and hypophysectomised rats were treated with saline or 0.4IU/body GH daily during 7 to 11 weeks of age. Histological features of the thymus and spleen and immunological parameters including blood cell counts, lymphocyte subsets, serum immunoglobulin levels, splenic natural killer activity, and mitogen-induced splenic lymphocyte proliferation were examined in the rats at 11 weeks of age.
In hypophysectomised rats, the counts of peripheral white blood cells (5,513±813/μl), lymphocytes (4,838±737/μl), Th/i cells (2,237±329/μl), and B cells (1,400±509/μl), Th/i/Ts/c ratio (1.78±0.27), splenic T cell subsets (pan T: 51.0±4.3%, Th/i: 31.6±3.0%, Ts/c: 23.9±2.7%), and serum IgG level (2,148±470mg/l) were significantly decreased as compared with normal rats. Natural killer activity (17.8±4.6%) and mitogen-induced proliferation of T cells (Con A: 47.1±15.7, PHA: 51.6±12.5) were also suppressed. Hypoplasia of the thymus and spleen was observed in parallel to retarded growth of the rats. In contrast, GH supplement to the hypophysectomised rats resulted in increases in growth and lymphoid tissue, and the restoration of the counts of peripheral white blood cells (6,850±840/μl), lymphocytes (6,211±731/μl), Th/i cells (2,909±304/μl), and B cells (1,947±402/μl), Th/i/Ts/c ratio (2.04±0.34), serum IgG level (3,414±1,326mg/l), and natural killer activity (25.7±4.7%). However, splenic lymphocyte subsets andmitogen-induced proliferation of T cells were not recovered by GH treatment for 4 weeks. GH administered to normal rats increased serum IgG level (4,982±1,496mg/l) but did not affect other immunological parameters.
These results indicate that humoral and cell-mediated immune function are impaired in hypophysectomised rats, but GH supplement administered to them restored most of the impaired immune function, suggesting that GH plays an important role in the development of immune function.抄録全体を表示PDF形式でダウンロード (3631K) -
深澤 信彦1991 年 67 巻 10 号 p. 1178-1185
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーBioBreeding/Worcester (BB/W) rats develop insulin dependent diabetes mellitus (IDDM) and lymphocytic thyroiditis (LT) spontaneously. Our previous studies have shown that BB/W (Saitama-Tokyo colony) rats develop LT at about 10 weeks of age. Their serum TSH values increase as LT extends, although their serum thyroid hormone levels remain normal. This indicates that BB/W rats suffer from subclinical hypothyroidism.
To investigate whether BB/W rats have a defect in iodide metabolism, the thyroidal radioactive iodine uptake (RAIU) in BB/W rats was examined. Thyroidal RAIU at 3hr in both 8 and 16 week-old BB/W rats was significantly higher than that in age-matched normal Wistar rats. On the other hand, BB/W rats had significantly lower 48hr thyroidal RAIU than normal Wistar rats. This suggests that BB/W rats appear to have some defects in iodide metabolism, especially in iodide organification even before the development of LT. The expression of thyroid peroxidase (TPO) and thyroglobulin (Tg) mRNA in BB/W and Wistar rats was then examined using the Northern blot analysis. The expression of both TPO and Tg mRNA was greatly decreased in BB/W rats compared with that in Wistar rats despite the high serum TSH levels in BB/W rats. This indicates that BB/W rats may have pretranslational defects in TPO and Tg synthesis, resulting in the impaired thyroid hormone synthesis.
In the present study, it has been demonstrated that BB/W rats appear to have a defect (s) in iodide metabolism possibly due to some abnormalities in TPO and Tg synthesis.抄録全体を表示PDF形式でダウンロード (1281K) -
樽谷 修, 吉村 弘一, 大森 毅, 細谷 東一郎, 石北 敏一, 石田 常博1991 年 67 巻 10 号 p. 1186-1196
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーIodination of the isolated thyroglobulin (Tg) by peroxidase was compared with various Tg preparations obtained from patients with thyroid diseases. For the purpose, the iodination process was observed in the incubation medium containing Tg, iodide, H2O2-generating system, and thyroid peroxidase (TPO) or lactoperoxidase (LPO).
During the incubation, iodination of Tg preparations increased gradually and reached a plateau after 90min., and 5 min. incubation with 3mIU or 14mIU of TPO, respectively. The degree of iodination level at the plateau region was different in each Tg preparation, depending on the iodine content of the original starting (native) preparation before incubation. The iodination level of cancer Tg with a very low iodine content (less than 0.1%) was low compared with the normal Tg level (obtained from normal thyroid tissue which contained about 0.4% iodine). The above findings suggest the possible existence of some structural differences of Tg in terms of the susceptibility to the iodination between the preparations of normal and diseased Tgs.
As far as the immunological aspect concerned, there was no significant difference in the affinity (avidity) of Tg with polyclonal anti-Tg antibody between the native Tg and the enzymatically iodinated one. These results suggest that the changes of iodine and thyroid hormone contents of Tg by in vitro iodination, has no significant effect on the immunological property of Tg molecule.抄録全体を表示PDF形式でダウンロード (865K) -
今井 強一, 渡辺 恵子, 高橋 修, 中田 誠司, 中沢 康夫, 山中 英寿1991 年 67 巻 10 号 p. 1197-1210
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーIt was reported that a new steroidal anti-androgen, TZP4238 (17 α-acetoxy-6-chloro-2-oxapregna-4, 6-diene-3, 20-dione), was 10 times stronger than chrolmadinone acetate (CMA) as the in vivo anti-androgenic potential. To confirm this result, the effect of TZP4238 and CMA on ventral prostates of intact rats, or castrated ones treated by testosterone, was investigated. Our experiments demonstrated that TZP4238 was 3-5 times stronger than CMA.
The effects of this compound on the androgen-receptor complex formation in the human and rat prostates were investigated and compared to the other anti-androgen and related compounds. An aliquot of cytosol or KCl extract from rat or human prostate was incubated with [3H] R1881 in the presence of various tested compounds. By means of dextran coated charcoal assay and sucrose density gradient centrifugation analysis, TZP4238 and TZP4239 showed a stronger inhibitory effect than other compounds except dihydrotestosterone. Judging from all these results, it was estimated that TZP4238 was 2-3 times stronger than CMA. The Scatchard plot analysis revealed that the inhibitory effect of TZP4238 was a competitive type. Between CMA and TZP4238, the difference of in vivo anti-androgenic potential was not identical with that of the inhibitory effect on the androgen-receptor complex formation.抄録全体を表示PDF形式でダウンロード (1102K) -
伊藤 直樹, 熊本 悦明, 赤樫 圭吾, 高木 良雄, 塚本 泰司, 丸田 浩1991 年 67 巻 10 号 p. 1211-1218
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーSome patients develop hypertension after adrenalectomy for primary aldosteronism. We treated 60 cases with primary aldosteronism, and the percentages of cases manifesting hypertensive blood pressures after operation were as follows: 40.0% at the first month, 24.2% at the second year, 30.4% at the 5th year after operation. What are the most important clinical factors relating to postoperative blood pressure? Knowledge of those factors would help in predicting the postoperative blood pressure in cases with primary aldosteronism.
The relationships between the postoperative blood pressure and several clinical factors were evaluated for a certain postoperative period using multiple regression analyses. The results were as follows: 1. The duration of preoperative hypertension is the major determinant at the second month after operation. 2. The histological findings for the kidney are the major determinant at the 6th month and the first year after operation. 3. At the second year postoperation, the histological findings for the kidney and the familial history of hypertension are the major determinant respectively. 4. The familial history of hypertension is the most determinant at the 5th year after operation.
It is concluded that the preoperative duration of hypertension and the histological findings for the kidney are helpful in predicting blood pressure during the first 2 years after operation, while the familial history of hypertension influences the postoperative blood pressure thereafter.抄録全体を表示PDF形式でダウンロード (834K) -
五十嵐 登, 佐藤 保1991 年 67 巻 10 号 p. 1219-1229
発行日: 1991/10/20
公開日: 2012/09/24
ジャーナル フリーWe presented a 16-year-old boy with severe growth retardation and markedly decreased levels of growth hormone-binding protein (GHBP) in plasma, which was shown to correspond to the extracellular composition of hepatic GH receptor and suggested to reflect tissue concentration of the receptor.
His height was 92.5cm (-13.5 SD), the weight 9.6kg (-5.8 SD) and Tanner stage was I. His bone age was 3.5 years old at 16 years of age. Karyotype was 46, XY and thyroid function was normal. SM-C levels, determined by Nichols RIA using unextracted plasma, were within the low normal range, 0.67/0.68U/ml. In contrast, using a method of acid-ethanol extraction, IGF-I and IGF-II levels were definitely low, 29ng/ml (normal 88-240) and 165ng/ml (374-804) respectively. GH responses in various provocation tests, including insulin, arginine and GRF, were within normal. Basal GH levels were 20±12ng/ml and urinary GH excretion rates 217±85pg/mg. Cr, which were elevated compared to age-matched control. Molecular size of his circulating GH was similar to control subjects. The biological activities of GH, evaluated by radioreceptor assay and Nb2 cell bioassay, were proportional to the immunoactivities of GH. SM bioactivities, which were determined by the stimulatory effects on DNA synthesis of rabbit costal chondrocytes and human fibroblasts, were apparently reduced. Electrophoretic pattern of IGF-binding protein was similar to those of GH deficient cases. Daily administration of hGH (4U/day) for 5 days resulted in a poor response of SM-C production (before 0.68, after 0.77U/ml). GHBP activities were definitely low by gel-filtration, immunoprecipitation and charcoal methods, as seen in Laron dwarfism which is defined as a syndrome of congenital GH receptor defects.
These results indicate that the tissue content of GH receptor in this case was quantitatively reduced and as a result, he showed a resistance to endogenous and exogenous GH. It remains to be elucidated whether the GH receptor defect in our case is derived from a genetic origin or an acquired condition.抄録全体を表示PDF形式でダウンロード (1494K)
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