From our experience in the treatment of anovulatory cycle with gonadotrophin (PMS and HGG) preparation it was observed that rather larger amounts of PMS were needed to succeed in the induction of ovulation in the repeated series of treatment than in tne first series (Table 1). This evidence is presumed to be due to the appearance of anti-PMS in blood.
Blood specimens were drawn from nine patients selected from the group who were treated with gonadotrophin. Anti-PMS titres were examined by using the haemagglutination reaction immunologically before and after the treatment (Table 2). Although no anti-PMS titres were observed in all the cases before the treatment, they markedly increased after treatment with some individual differences. Blood specimens from seven patients who were treated with repeated gonadotrophic therapy 15-30 weeks after the first therapy, were tested by the same method (Table 3). In some of them anti-PMS titres were still seen before the second series of injections. Generally, titres of anti-PMS increased rapidly and continued at high level after the second treatment.
Biologically, 1 ml of serum obtained from a patient who showed 1,024 of anti-PMS titre inactivated completely 2 IU of PMS in uterine weight on CF 1 female immature mouse (Table 4). This anti-serum was diluted by the 2-fold method and tested in the same way. As a result it was recognized that 1 ml of anti-serum up to 64 of titre did not neutralize 2 IU of PMS (Table 5). Specimens drawn from six patients who showed various different titres gave the same results as above (Table 6).
These results obtained indicate that anti-PMS which can neutralize PMS activity appears after the successive injection of PMS in all cases. For this reason gonadotrophic therapy must be carried out carefully with a rational schedule.

抄録全体を表示

As a part of studies on intermedia pituitary hormone (MSH), the isolation of MSH-like substance from human urine was performed to prove that MSH occurred in urine. And the physical and chemical properties of this MSH-like substance were characterized. Furthermore. their physico-chemical properties were investigated. On the other hand, it has been known that the regeneration of visual purple in the isolated retina was augmented by MSH which had relations to Retinitis Pigmentosa.
In this paper the physico-chemical difference between the MSH-like substance from normal adult urine and Retinitis Pigmentosa patient's urine is made clear and Retinitis Pigmentosa is suggested as endocrinological metabolic disease.
(I) Isolation of MSH-like Substance from Human Urine and its Properties.
The active material is extracted with warm acetic acid from urine, precipitated with acetone-ether mixture and purified by the charcoal adsorption procedure. Further purification is carried out by ion exchange chromatography. This MSH-like substance is a slightly basic polypeptide which migrates as a single band when it is submitted to ionophoresis on paper in pyridine-acetic acid buffer at pH 6.5. It seems that their physical properties are very similar to the MSH from human pituitary gland.
(II) Physico-chemical Properties of Urinary MSH-like Substance
(1) This substance possesses a melanocyte expanding activity and inhibits the influence of large doses of Vitamin C which suppress a melanocyte expanding action, in the same way as that of MSH from pituitary gland.
(2) This substance auguments the activity of tyrosinase by Kobowitz's method at 10 min. after initiation. This effect is the same as that of MSH from pituitary gland.
(3) This substance decreases the level of Vitamin A in rat liver, and increases the urinary excretion of estrogen in rabbit.
(4) This substance expands slightly the amplitude of heart palpitation on Bufo, but does not affect to the blood pressure in rabbit.
(III) Difference between the Urinary MSH-like Substance of Normal Adult and that of Patient
(1) The urinary MSH-like substance from patients does not posses the activity of melanocyte expanding.
(2) This substance from diseased urine does not show the effect of decreasing Vitamin A level in rat liver and of increasing urinary estrogen excretion in rabbit.
(3) This substance from diseased urine has no absorption at 1100cm^-1 of ultra-red absorption spectrum.

抄録全体を表示

It was recently reported by Taurog that extraneous ¹³¹I components appeared on filter paper chromatograms of carrier free radioiodide solutions when the samples applied to filter peper were allowed to dry in air before the strips were placed in the chromatography jars.
The present study was undertaken to observe similar findings in HVEP.

抄録全体を表示

The present studies were undertaken to investigate the influence of a proteolytic enzyme in plasma-plasmin-on the inactivation of ACTH.
1) ACTH (the third international standard ACTH) was incubated for one hour in human plasma with various concentrations of streptokinase which were added to activate plasminogen. The remaining activity of ACTH after the incubation was assayed by the adrenal ascorbic acid depletion method. The activity of ACTH in medium decreased as the concentration of streptokinase increased, and there was parallelism between the decrease of ACTH and the increase of plasmin activity in plasma assayed by caseinolysis. When human euglobulin fraction was used in place of human plasma, ACTH was fully inactivated by less streptokinase. Without addition of streptokinase, ACTH was scarcely inactivated by either human plasma or euglobulin fraction.
2) Crude ACTH (NEWHOUSE ACTH), highly-purified ACTH and synthetic β^1-24 ACTH, each of which was made to have an equivalent biological activity, were incubated for 30 minutes in human euglobulin fraction with the addition of streptokinase. Under the condition in which crude ACTH was not inactivated in 30 minutes, the activity of highly-purified ACTH decreased to 76.3% and that of synthetic β^1-24ACTH to 58.1%. The difference of the rate of inactivation in vitro between the ACTH preparations may explain the difference in duration of the action between them in vivo.
3) Recently, Nagamatsu et al. synthesized new antiplasmin lysine derivartives, of which N, N'-dicarbobenzyloxy-L-lysine (DCL) and N, N'-dicarbobenzyloxy-L-lysyl-N^ε-carbobenzyloxy-L-lysine (TCL) were reported to be more potentin in hibiting the proteolytic activity of plasmin than ε-aminocaproic acid (ε-ACA). These plasmin-inhibitors (ε-ACA, DCL and TCL) were examined for their inhibitory effects on the inactivation of ACTH by the plasma-streptokinase system. Both DCL and TCL inhibited the inactivation of ACTH in vitro by 50-60%. DCL was effective at the concentration of more than 4.6 × 10^-5M and TCL of more than 2.8 × 10^-5M. But ε-ACA showed no inhibitory effect on the inactivation of ACTH even at such a high concentration as 5.8 × 10^-3M.
4) The activity of ACTH in vivo was assayed by plasma 11-OHCS levels in rabbit treated with prednisolone. Plasma 11-OHCS decreased to the minimum levels in one hour after a single prednisolone administration and remained constant for at least 3 hours. Streptokinase with a trace of human serum as a source of proactivator of plasminogen was injected intravenously to activate plasmin in rabbit plasma. Plasmin activities in rabbit plasma were assayed by clot-lysis time.
After the administration of ACTH, plasma 11-OHCS showed maximum value at 30 minutes, and returned to the basal level in 150 minutes. The response of plasma 11-OHCS to ACTH was suppressed when streptokinase was given 30 minutes before the administration of ACTH. Intravenous injection of a plasmin-inhibitor (DCL) 15 minutes before ACTH potentiated the activity of infused ACTH. These results indicate that the activation of plasmin system in vivo suppresses the action of ACTH, and that the inhibition of plasmin activity in vivo makes infused ACTH long-acting.

抄録全体を表示

Analysis of endometrial aspiration smear were used to determine the effects produced by various substances with progestational activity on the endometrium.
The results obtained were based on 24 women aged from 26 to 34 years, who showed regular menstrual cycles with no gynecological disorders.
The 19-nor-testosterone derivatives brought marked elevation of the basal body temperature. These compounds mainly caused significant changes on the endometrium without any effects on the stromal cells. Progesterone, retroprogesterone and estrenol derivatives brought neither marked elevation of the Basal Body Temperature nor any significant changes in the endometrial glandular cells.
However, the stromal cells showed considerable atypism. The 17-α-acetoxyproge-sterone derivatives had only moderate effects on the glandular cells as well as on the stromal cells.
The change in the glandular cells, particularly caused by 19-nor-testosterone derivatives were roughly proportional to the degree of elevation of the Basal Body Temperature.
The many kinds of stromal atopism, caused by progesterone, retroprogesterone and estrenol derivatives were inversely proportional to the basal body temperature changes.

抄録全体を表示

In order to investigate the conditions of autonomic nervous system and adrenal medullary function of patients with bronchial asthma, changes in urinary excretions of catecholamines (CA), total metanephrine (MN) and vanillyl mandelic acid (VMA) were ovserved in asthmatic patients as well as in rabbits with experimentally induced asthmatic attack, and the following resultes were obtained :
1) Comparison of 24 hour volumes of urinary CA, total MN and VMA excretions among 23 normal persons and 14 asthmatic patients in a stable condition, disclosed no remarkable difference except for a slight increase of noradrenaline (NA) in the latter.
2) Asthmatics in a stable condition show greater daily and diurnal variations in urinary adrenaline (A), NA and VMA excretions than normal persons. In normal persons, urinary A, NA and VMA excretions reach a peak in the afternoon and decrease at midnight, but in asthmatics these diural circles are not seen.
3) The measurement of urinary excretions of CA and their metabolites before, during and after the asthmatic attack revealed the following : (1) Just before the attack, there are no remarkable change in urinary A, NA, total MN and VMA excretions. (2) During the attack, urinary A increases in a few patients and urinary NA in a half of them. There is no patient whose urinary A or NA decreases, but urinary total MN and VMA decrease in almost all of them. (3) In the recovery phase from the attack, urinary A, NA, total MN and VMA increase in all of them.
4) Clinical pictures and urinary CA and VMA are observed after the subcutaneous injection of 0.1% adrenaline hydrochrolide 0.5ml. About 5% of the administered A is excreted without any metabolic change for 3 hours after the injuction, and VMA excreation volume increases slowly in normal persons. The excretion rate of the administered A from the patient who recovers soon after the injection is not different from that of normal persons. But though the excretion rate of unmetabolized A is as high as 6 to 7% in the patients who do not recover well, VMA excretion does not increase in 5 hours after the injection.
5) When adrenocortical hormone or antihistaminies is administered to normal persons, urinary A, NA and VMA do not change significantly. When a teophylline derivative is administered to them, urinary A, NA and VMA increase slightly.
6) When 1% pilocarpine 0.5ml is injected subcataneously into normal persons and asthmatics, urinary A, NA and VMA increase equally in both groups. In no one, however, is induced asthmatic attack by this treatment.
7) Experimental asthma is induced by acetylcholin-, histamine- and ovalbuminaerosol in rabbits. In the cases of the acetylcholin- and histamine-asthma, urinary A and NA increase apparently during the attack and decrease to normal level soon after the attack, but urinary total MN and VMA increase and return to the normal rather than A and NA. In the case of allergic asthma, urinary A and NA during the attack are the same as in the pretreated cases, and urinary total MN and VMA during the attack are less than in the pretreated. All these substances increase after the allergic asthmatic attack.
8) The rabbit group in which asthmatic attack can be induced by ovalbumin as an antigen are compared with a group in which it can not be induced. There is no remarkable difference between the two groups before the treatment. But when an asthmatic attack by acetylcholin- or histamine-aerosol is induced in each group under the same conditions, the grade of the attack and the increase of urinary A, NA, total MN and VMA of the former are more remarkable than those of the latter.
From these results the following conclusions may be reached :
(1) The tension of sympathic nervous system and the adrenal medullary function are labile in patients with bronchial asthma. (2) The asthmatics have latent insufficiency of these functions ; therefore, this is one of the causes of asthmatic attack.

抄録全体を表示

Peroxidase activity in each fraction of cow thyroid, mitochondria, microsome and soluble fraction, was measured by Ettoris' and modified Randall's method which was manometric measurement of peroxidase activity.
The influence of TSH upon peroxidase activity was studied by the modified Randall's method, adding TSH to the substrate.
Peroxidase activity was also estimated from oxygen consumption with Warburg's manometer by using glucose glucoseoxidase system as H₂O₂ donor.
Iodination of l-tyrosine in the reacted solution was traced by paperchromatography.
The results were as follows :
1. Peroxidase activity is highest in the microsomal fraction, and lowest in the mitochondrial fraction. It is presumed that peroxidase activity in the mitochondrial fraction was probably the result of a contamination by the microsomal fraction. No peroxidase activity is found in the soluble fraction, supernatant.
2. It is thought that TSH directly accelerates activation of peroxidase.
3. When reaction time exceeds 20 minutes in the glucose glucoseoxidase system as H₂O₂ donor, it is found that non-enzymatic oxidation of iodine ion becomes more active as time goes by.
4. TSH stimulates glucose oxidation.
5. By paperchromatography MIT and DIT were not found in the reaction media, in which cow thyroid is added as an enzyme.
Unexpectedly, no iodized amino acids were found in the media, in which MIT had been added directly.
From this fact, it is assumed that deiodinase is included in the preparation of cow thyroid which is a crude enzyme and this might split iodine from the amino iodides which have been produced in the reaction media.

抄録全体を表示