The ¹²⁵I-C_1q binding test for the detection of soluble immune complexes in native unheated human serum was applied to the study of sera from 52 patients with diabetes mellitus in childhood. This radiolabeled C_1q binding testis more sensitive and reproducible among the various methods proposed for the detection of immune complexes.
The ¹²⁵I-C_1q binding activity in 52 sera from diabetes mellitus in childhood was 9.47±0.36% compared to 6.94±0.74% in normal controls.
¹²⁵I-C_1q binding values in diabetes mellitus in childhood were significantly higher than normal controls. Slight high values were seen in 3 patients with positive anti-DNA-antibodies in diabetes mellitus in childhood. ¹²⁵I-C_1q binding was not significantly increased in patients with positive antithyroid antibodies and insulin antibodies. There was no significant correlation between the duration of diabetes and ¹²⁵I-C_1q, binding activity.

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We studied the effects of the administration of dexamethasone (DX) with or without thyrotropin releasing hormone (TRH), thyroxine (T4), growth hormone (GH), and prolactin (PRL) on the plasma 3, 5, 3'-triiodothyronine (T3), 3, 3', 5'-triiodothyronine (rT3), T4, thyrotropin (TSH), GH, PRL, insulin, and milk production in36 normal lactating cows. A single subcutaneous injection of 10mg DX resulted in 21% reduction in milk production on the following day. While plasma rT3level increased 1.4 fold, plasma T3 concentration reduced by 52% 24hr after DX injection (p<0.001). Reduction in plasma TSH and T4 levels was small and no significant depression of plasma GH and PRL was detected. A prompt and prolonged increase in plasma insulin concentration was observed. Simultaneous injections of 10mg DX with 2mg TRH followed by an additional injection of the same dose of TRH5hr later, resulted in no depression of milk production. Plasma T3, insulin, GH, and PRL levels 5hr after the first hormone injection was significantly elevated. Plasma T4and rT3 concentrations 24hr after the injection increased 1.78 and 3.2 fold, respectively (p<0.001), but the levels of T3, GH, and PRL returned to their pre-treatment levels. The mean plasma GH level significantly increased. In the control cows, neither plasma hormone levels nor milk production significantly changed. The injection of 10mg T4 or 20mg GH twice a day with an administration of 10mg DX reduced the milk production by less than 9% on the following day. On the other hand, no preventive effect of concomitant administration of PRL (54mg×2) with 10mg DX on depression in milk production was detected. Plasma T3 level 24hr after the simultaneous administration of DX with T4 was 1.65times as high as the pre-injection level and the level continued for several days. However, plasma T3 reduced by 40% 24hr after the administration of either DX+GH or DX+PRL. The preventive effect of TRH on the depression of milk production caused by DX might be partly derived from a synergistic action of the enhanced circulating levels of thyroid hormones and GH. A possibility of additional favourable TRH actions on lactation other than through adenohypophysis also exists.

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We describe the natural recovery from the aggravated hypertension, hypokalemia and suppression of the renin-aldosterone axis after the glycyrrhizin discontinuation in two mild hypertensive women aged 71 and 68 years, who had been administered 273 to 546mg glycyrrhizin daily for 1.5 and 6 months, respectively, for the treatment of liver disease. About one month after the glycyrrhizin discontinuation, acceleration of hypertension, hypokalemia and suppression of the renin-aldosterone system still continued in both patients. At this stage, sodium restriction resulted in the normalization of blood pressure with weight loss and the subsequent sodium repletion produced a rapid increase in blood pressure to hypertensive levels observed before sodium restriction, with weight gain. Plasma renin activity and plasma aldosterone were low and did not respond to sodium restriction. Inappropriately excessive amounts of potassium were also excreted in the presence of hypokalemia. About one and a half months later, the improvements of aggravated hypertension, hypokalemia and suppressed renin-aldosterone system gradually occurred in both patients. Sodium restriction performed about three months later in case 2 no longer produced the changes in blood pressure and body weight. Plasma renin activity and plasma aldosterone responded subnormally to sodium restriction.
These results demonstrate that both patients had a prolongation of the syndrome resembling primary aldosteronism except the low plasma aldosterone level about one month after the glycyrrhizin discontinuation. The possible mechanisms by which this prolongation was caused are discussed.

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The effects of the electric stress on glucose oxidation, cyclic adenosine 3', 5'-monophosphate (AMP) accumulation and ⁴⁵Ca⁺⁺ efflux in response to glucose were studied in pancreatic islets isolated from rats fed on a control (C) or a high fat diet (F) for 12 weeks.
The half of rats on each diet were subjected to electrical shocks in the random time schedule for1hr per day for the last 3 weeks of the feeding period (group C-S and F-S). The remaining rats were not given any shocks (group C-NS and F-NS). The rats in F-S group had the high levels of plasma epinephrine, dopamine and blood glucose. The basal content of cyclic AMP after 20min of incubation with 2.8mm glucose was decreased in islets from F-S group without affecting insulin release. After 20min of incubation with 25mm glucose, the cyclic AMP content in islets from F-S group, which was identical with that in F-NS group, was only 50% of that in C-S group. Insulin release in response to high glucose was significantly inhibited in islets from F-S group. In spite of a remarkable increase of cyclic AMP content in islets from C-S group, insulin release did not differ from that in C-NS group. Glucose (16.7mm)-stimulated ⁴⁵Ca⁺⁺efflux from the perfused islets was greatly inhibited by the high fat diet rather than by stress. The rate of glucose oxidation with 16.7mm glucose was decreased in islets from F-S group.
It is suggested that the decreased insulin release in response to glucose provoked by the combined effects of the feeding of a high fat diet and electric stress may be mediated by changes of the adenylate cyclase-cyclic AMP system on the plasma membrane of the B-cell or be related to changes in glucose metabolism in islets.

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The concentration of somatomedin A (SMA) in various rat tissues was determined directly by the radioreceptor assay in supernates of tissue homogenates at 100, 000×g for 60 min. The SMA concentrations in pancreas, kidney, lung, liver, spleen, testis, brain and muscle were 2.56, 2.40, 2.28, 2.16, 1.56, 1.44, 0.60 and 0.30U/g of wet tissue, respectively. The SMA content in rat serum was 6.66U/ml. The SMA concentration in tissues never exceeded that in serum. When the100, 000×g pellet of liver was treated with a hypotonic solution, the SMA content in the hypotonic solution was about 35% of that in the initial supernate. This result indicates that about30% of the SMA in liver was stored in organellae. SMA in tissues decreased with incubation at 37°C, though SMA in serum did not. This decrease could be precluded by adding 0.75mm HgCl₂ to the liver homogenate. The SMA content of the liver homogenate was dependent on growth hormone in experiments both in vivo and in vitro.

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Degradative activities of somatomedin A (SMA) have been examined in various tissue homogenates of rats using trichloracetic acid precipitable radioactivity of125ISMA. Kidney and testis showed higher specific activities and liver and brain lower activities. They were dependent on SH reagents; 0.5mM HgCl₂ inhibited the degradative activity of liver completely and1mM dithiothreitol (DTT) augmented the activity slightly. The activities in liver were separated by differential centrifugation; about 90per cent of the total activity in the whole homogenate was recovered in the supernatant fraction at 100, 000×g for60min, and 10per cent in the precipitate. The pH profile of each fraction was different; that of the supernatant showed a single peak at pH7.4and that of the pellet revealed two peaks at pH5.9 and 7.4. However, both fractions showed similar SH-dependency.

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The concentrations of human chorionic gonadotropin (hCG) and its free immunoreactive alpha-subunit (hCG-α) in the sera of patients with trophoblastic diseases were measured by hCG and hCG-α radioimmunoassay (RIA), respectively.
In the sera of 12women with hydatidiform mole large amounts of hCG and considerably high level of hCG-α were detected in all cases. After the evacuation of mole the serum level of these glycoproteins decreased, the level of hCG-α declined more rapidly than hCG.
In the sera of patients with destructive mole the concentration of hCG-α was usually lower than that of hCG. After hysterectomy and chemotherapy the levels of hCG-α declined practically paralleling that of hCG. However, when hCG had decreased to undetectable level, hCG-α could no longer be detected in all cases.
Although in the serum of patient with choriocarcinoma involving the uterus and lungs the concentration of hCG-α was almost as high as that of hCG, the secretory pattern of hCG and hCG-α might not be closely related. The changes in the serum level of free hCG-α as well as that of hCG paralelled the clinical course of the patients examined in this study. The present results suggest that measurements of the serum free hCG-α may be a useful parameter to follow the clinical course and to evaluate the efficacy of treatments of trophoblastic diseases.

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This study was designed in an attempt to elucidate a mechanism of somatostatin inhibition of glucose-induced Ca²⁺ uptake by rat pancreatic islets.
Rat pancreatic islets were perifused with Krebs-Ringer bicarbonate (KRB) buffer containing16.7mM of glucose with somatostatin (2μg/ml) or/and diltiazem HCl (2×10^-5M). Somatostatin inhibited preferentially the early phase of glucose-induced insulin release, whereas diltiazem HC1 inhibited the late one. And the concomitant presence of the submaximal concentration of somatostatin (2μg/ml) and diltiazem H1l (2×10^-5M) provided the completely additive inhibition of glucose-induced insulin release.
Rat pancreatic islets were incubated with KRB buffer supplemented with 16.7mM of glucose and ⁴⁵CaCl₂ (10μCi/ml) for 5-60 min and the biphasic ⁴⁵Ca uptake by pancreatic islets was obtained. Somatostatin (500ng/ml-4μg/ml) gave the suppressive effect on the early phase of glucose-induced ⁴⁵Ca uptake, but the higher concentration (2μg/ml) of somatostatin did not impair the late phase of ⁴⁵Ca uptake by pancreatic islets.
On the other hand, diltiazem HCl did suppress the late phase of glucose-induced ⁴⁵Ca uptake dose-dependently, but did not suppress the early phase (2×10^-5M).
These data indicate that somatostatin suppresses the early phase of glucoseinduced Ca²⁺uptake preferentially to the late one and has a different action mechanism from Ca antagonist on glucose-induced insulin release.

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To examine the involvement of renin-angiotensin-aldosterone system in the etiology of oral contraceptive induced hypertension, normal women (Group I), normotensive (Group II) and hypertensive (Group III) women taking Ovulen (R) were infused with a competitive angiotensin II (AII) antagonist, [1-sarcosine, 8-isoleucine] angiotensin II. The angiotensin II antagonist was infused at a rate of 600ng/kg/min for 30min 1.5hrs after intravenous injection of40mg of furosemide. Blood pressure was monitored and pre-infusion and post-infusion plasma renin activity (PRA) and plasma aldosterone concentration (PAC) were determined.
Pre-infusion PRA and PAC showed no significant differences among these three groups. In response to the AII antagonist infusion blood pressure rose in Groups and II, but blood pressure responses in Group III were variable. Four out of the total 6 subjects had pressor responses and only one subject had a significant blood pressure reduction. In both Groups I and II, PRA decreased and PAC rose after infusion of the antagonist. In Group III, PRA decreased to a lesser degree and PAC showed no consistent change. These data suggest that the renin-angiotensinaldosterone system in hypertensive women or oral contraceptives is different from that of the normotensive users. However, the pathophysiology of oral contraceptive induced hypertension is not homogenous and angiotensinogenic hypertension is uncommon.

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Thyroid antimicrosomal antibodies, gastric parietal cell antibodies (PCA) and antinuclear factors were studied in 208 insulin dependent diabetic (IDD) according to the duration of diabetes and patient's age at the time of testing. Antimicrosomal antibodies were found in 11 out of 47 (23.4%) IDD with the duration of less than one year, however this value declined to 13.1% at1to 3 years, 15.3% at 4 to 5 years, 10.8% at 6 to 10 years and 5.8% at more than 10 years. Of the 47 IDD, 7 (14.8%) were positive for gastric parietal cell antibodies. The prevalence of PCA declined with the increasing duration of diabetes.
However, this decrease in the prevalence of antimicrosomal antibodies and PCA was not so extreme as that of pancreatic islet cell antibodies. Antinuclear factors did not reveal a significant correlation with the duration of diabetes.
In normal controls, the prevalence of antimicrosomal antibodies, PCA and the antinuclear factors increased progressively with age. In IDD, the prevalence of the antinuclear factors was also progressively greater with age. However, the prevalence of antimicrosomal antibodies in IDD decreased with age and those of PCA showed the lowest percent in the 40-69 year-age group.

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The effect of calcitonin (CT) on Ca-ATPase activity in the plasma membrane fraction of rat liver was investigated. CT (80 MRC mU/100g BW) administered subcutaneously to rats, caused a significant decrease in serum calcium, while increasing liver calcium. The administration of CT produced a rapid decrease of Ca-ATPase activity in the plasma membrane fraction of liver, whereas CT did not cause a significant alteration of p-nitrophenyl phosphatase activity. The maximal response of CT was obtained with 80 MRC mU/100g BW. Meanwhile, the administration of imidazole (30mg/100g BW) which has a hypocalcemic effect, like CT, produced a significant increase in liver calcium and a corresponding fall in Ca-ATPase activity of the plasma menbrane fraction. The reduction of Ca-ATPase activity produced by imidazole was significantly potentiated by the simultaneous administration of CT, and the rise in liver calcium was enhanced slightly. The present results suggest that the action of CT on liver calcium involves the decrease of Ca-ATPase activity in the plasma membrane of rat liver.

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Two patients with post-partum transient thyrotoxicosis associated with painless thyroiditis and low radioactive iodine uptake were described. The surreptitious use of thyroid hormones or iodine was excluded. Although the clinical course was compatible with that of subacute thyroiditis, passing through the hyperthyroid, euthyroid, hypothyroid and recovery phase, the patients showed a sustained elevation of serum anti-thyroglobulin antibody titer during the entire phase of the disease. Moreover, the histological findings obtained by the thyroid biopsy performed in a case were characteristic of chronic lymphocytic thyroiditis. Furthermore, it was of interest that the disease recurred following every delivery in 2 cases, suggesting the possible role of immunological changes induced by pregnancy and delivery in the etiology of this disease.

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Thyroxine (T4)-prolactin interactions on hepatic arginase and ornithine transcarbamylase (OTC) as well as hind legs, tail, digestive tract and median eminence were investigated in tadpoles, Rana catesbeiana.
Prolactin completely blocked T4-induced tail resorption, but failed to suppress hind-leg growth, shortening of digestive tract and promotion by T4of the median eminence development. Prolactin blocked T4-induced increase in hepatic arginase activity but not in hepatic OTC activity.
A possibility that T4and prolactin are regulating the hepatic arginase indirectly is discussed.

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A girl aged4years with goiter and accelerated physical and skeletal growth was found to be hyperthyroid on the basis of elevated serum thyroid hormone level, nevertheless both the basal TSH and TSH responsiveness to TRH were maintained within the normal range. Serum TSH was suppressed by exogenous T3 and dexamethasone administration, but not significantly changed after propylthiouracil (PTU) treatment. The diurnal rhythmicity of anterior pituitary hormones was preserved with the high nocturnal peak of TSH and prolactin. Clinically, neither thyrotoxic signs nor evidences of pituitary tumor were observed. Her accelerated growth and elevated thyroid hormone level appeared to be induced by inappropriate secretion of TSH. In view of the literature, this is the first case of the syndrome of inappropriate secretion of TSH excluding the neoplastic origin in Japan.

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In 5 normal men an intravenous injection of 0.5mg of synthetic^1-24ACTH caused a significant increase in plasma aldosterone and a simultaneous intravenous infusion of 600ng/kg/min of des-asp¹-, ileu⁸-angiotensin II (AIIIA) did not inhibit this increase. Since this dose of AIIIA is known to inhibit an angiotensin IIinduced increase in plasma aldosterone in normal men, the present results suggest that the ACTH-induced aldosterone stimulation is mediated by an adrenocortical receptor which is different from angiotensin II receptor.

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The serum estradiol concentration and bone mineral content of the right radius were determined in 34 postmenopausal females. Regression analysis showed a significant positive correlation between the serum estradiol concentration and bone mineral content of the right radius (r=0.477, p<0.01). These results support the view that the decreased level of serum estrogens is one of the major factors involved in the loss of bone mass with age.

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