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The minimal effective dose of a preparation of porcine FSH was determined by the assay based on the resumption of ovarian follicular development and the increase of ovarian weight in hypophysectomized immature rats. This preparation contained about 23% of ICSH by the ventral prostate assay in hypophysectomized rats. At doses of 50100γ the minimal stimulation of follicles was detected microscopically, and the follicular growth was evident at a dose of 200γ. In this dose, the definite increase of ovarian weight was, also, observed.From these results, total dose of 200γ of the preparation of FSH was determined to be the minimal effective dose stimulating both the follicular development and the ovarian weight increase.

Effects of the combined treatment with the minimal effective dose of purified swine FSH (200γ) and the various levels of purified sheep ICSH (LH) on the ovaries and the uteri of hypophysectomized immature female rats were studied. The experimental conditions were the same as that of the previous report5) except that FSH and ICSH were injected separately into the underskin at different sites of the body.On injection of 200γ of FSH alone, ovaries and uteri were increased in weight. This dose of FSH caused the development of follicles with stimulated internal theca cells and without repair of the deficient interstitial cells. The ovarian and uterine weights were barely increased by the large dose (1 mg) of ICSH. The most conspicuous effect of ICSH was the stimulation of the interstitial tissue. The augmentation of the effect of 200γ of FSH on the increase of ovarian and uterine weights was not conspicuous by combination with ICSH. The histological examination demonstrated that the interstitial tissue was highly stimulated and the follicular growth with the development of internal theca cells was somewhat augmented, but no thecal luteinization nor formation of corpus luteum was detected. The stimulative effect of FSH on estrogen secretion, estimated by the uterine development, was not so increased by the combined treatment of ICSH. The authors (1957) found that FSH is the potent substance to induce ovulation in adult rats8).By these results, it would be said that the main effect of ICSH on the ovary may be the stimulation of interstitial tissue, and FSH might play more important role to cause the formation of corpus luteum.

Studies were made on the transient responses of rat ovulation and vaginal smear to the reversal of the daily lighting schedules. Two kinds of lighting schedule, which were reversal each another, were used. One of the lighting schedules was normal lighting schedule, coinciding with the solar day, in which fluoresent lamps were switched on at 5 a.m. and switched off at 7 p.m. The other was artificially reversed lighting schedule in which the lamps were switched on 7 p.m. and switch-ed off at 9 a.m. These lighting schedules were consisting of 14 hrs. of light and 10 hrs. of darkness and were automatically regulated by a time switch. The vaginal smear was taken twice daily at 9 a.m. and 7 p.m. The ovulation was examined by the discovery of ovulated ova in the ampulla of the oviduct.The rats, which were exposed to the reversed lighting schedule and confirmed the synchronization of their vaginal smear to the lighting rhythm, were transfered into the condition of the normal lighting schedule at 7 p.m. of the each stage of their estrous cycle, and the shift of the time of ovulation after the transference was examined as well as the change of the vaginal smear.The ovulation in the normal lighting schedule and in the reversal lighting schedule respectively take place between 1 and 2 a.m. and between 3 and 5 p.m. of the following darkness of the proestrous stage. The synchronization of the vaginal smear to the normal lighting rhythm is not recognizable within 4 days after the reversal, but confirmable within 8 to 16 days in almost all rats. The synchronizaton of the ovulation, on the other hand, is more readily achieved than that of the vaginal smear, by delay of the ovulation at the rate of 1-2 hrs. per day.

The authors, in order to perform the analysis of luteal functions, measured progesterone (called P. hereafter) and pregn-4-ene-20α-ol-3-one(called 20-OH-P. hereafter) in the ovarian venous blood of rats, in the various stages of reproductive cycle. The ovarian venous blood 3-7 ml was collected for 2-4 hours by a cannula fitted to a branch of the ovarian veins and was extracted by a modified method of SHORT'S, and was developed on paper-chromatography (Heptane-Formamide), then the absorptions of UV (240 mμ) of each portion of the paper were sought and plotted for densitogram, and by pranimetry of the areas occupied by each of the peaks, P. and 20-OH-P. were calculated and quantitatively analyzed.(1) P. during normal estrus temporarily increases in the afternoon of proestrus when the ovulating hormone is released from hypophysis, its concentration reaches approx. 110 μg/100 ml blood which is equivalent to about 1/3 of that of the second half period of gestation, then somewhat increases in early, diestrus when the corpus luteum develops most. 20-OH-P. is found throughout the estrous cycle, and its maximum value is approx. 240 μg/100 ml blood. That is to say, the ovary of rats secretes P. even during the normal estrous cycle, but the secretion does not last long.(2) P. during gestation is already high on its 4th day and raises to the maximum value of the 15th day, but it is markedly low immediately before and after the parturition. On the other hand, 20-OH-P. showes rather lower value in the first half period of gestation than in normal estrous cycle, but it reaches appox. 260 μg/100 ml blood on the 15th day. This high concentration is found once more immediately after the parturition. The picture of 20-OH-P. showes a characteristic difference from that of P., although it has been reported there was a parallel relationship between P. and 20-OH-P.(3) P. on the 8th day of lactation is secreted in quite a high concentration, and by the fact that P. of the rat having 6 sucklings is higher than that of the rat haviug 2 sucklings in concentration, it is demonstrated that the secretion is evidently affected by the strength of suckling stimulation. With regard to 20-OH-P., the concentration is low and no difference is observed as in the case of P.(4) The ovary of rats hypophysectomized and bearing pituitary graft undeneath renal cupsule, secretes a large amount of P., but a little of 20-OH-P.

下垂体投与による成熟雌ラット排卵誘起反応を用い,発情前期午後の排卵ホルモン放出に伴う下垂体排卵ホルモン含量の減少を量的に調べ,且つ注射方法を吟味した。(1)発情前期10~12a.m.の下垂体排卵ホルモン含量は発情前期6~7p. m.のそれの大凡2倍である。(2)発情前期6~7p.m.の下垂体1個の排卵誘起能を皮下注射法でしらべれば,排卵ホルモン放出の有無を一応推定することが可能である。(3)静脈注射法は発情前期10~12a.m.の下垂体ホルモン含量の1/12~1/24個分で使用動物の50%に排卵を誘起させることが出来,皮下注射法より6~12倍鋭敏であるが,用量反応曲線が緩かなため,下垂体ホルモン含量の減少を検出するには適当でない。

This is a result of experiments which confirmed the biological activities of a preparation of sheep ICSH (LH) used in the course of studies on the actions of gonadotrophins. The effects of relatively large doses of the preparation of ICSH on the reproductive system of hypophysectomized immature female rats were studied. The significant increase of ovarian weight and the follicular development was not observed in all dosage levels. The interstitial cells were, already, repaired at a dose of 50γ which was the minimal dose adopted in this experiment. No corpus luteum was formed even at a large dose of ICSH (1000 γ). The uterine weight increased, slightly, at doses more than 200 γ. These results were almost the same as those given by the previous workers who used the pure sheep or porcine ICSH.

Regions of herpes simplex virus type 1 (HSV-1) DNA with variation in the size of restriction endonuclease fragments were identified by comparison of the BamHI, KpnI or SalI restriction endonuclease digestion patterns among 15 HSV-1 isolates after hybridization with specific 32P-labeled cloned HSV-1 DNA fragments. Of the types of restriction fragment polymorphism identified, one was a strain with a distinctly different restriction fragment than the prototype (loss or gain of restriction sites). Another type, the specific fragment varied only in size among strains. Thirteen distinct variations were identified. Ten were mapped to the unique sequence of the L component; two to the inverted repeat of the L component and one to the inverted repeat of the S component. The presence of a common ancestor from which some isolates of HSV-1 might derive was deduced from an analysis of the distribution of the thirteen variations among the 15 HSV-1 isolates.

The intra-articular structure of the elbow joint was studied in 18 patients with double contrast arthrography and tomography. All tomographic examinations were made with the hypocycloid motion. The authors feel that the disadvantages of the method, i.e., getting access to tomographic equipment, the 30 to 45 minutes required to complete the examination, and the radiation from multiple exposures needed for tomographic sections are obviated by the results: the arthrographic findings were confirmed in all 7 patients who later underwent surgery.

A novel method for the preparation of Kyn 62-lysozyme, in which tryptophan 62 is replaced by kynurenine, is reported. Hen egg-white lysozyme was ozonized in aqueous solution to yield one N'-formylkynurenine residue and deformylated with hydrochloric acid in frozen solution at -10 degrees C. Crude Kyn 62-lysozyme was purified by affinity and Bio Rex 70 chromatography successively. Kyn 62-lysozyme retains affinity for chitin and is essentially an active enzyme with a slightly weakened but distinct catalytic activity. After this modification, the enzyme activity was changed differently depending on the kind of substrate. At the individual optimum pH's, lytic activity was largely retained (80% active), but the catalytic efficiency for hydrolyzing glycol chitin was relatively low (30% active). Lysis of M. lysodeikticus cell suspensions was optimally catalyzed by Kyn 62-lysozyme at pH 6.2 and at 0.088 ionic strength. These values are lower by 1.3 pH unit and 0.04 ionic strength, respectively, than those of intact lysozyme. The optimum pH and ionic strength for the hydrolysis of neutral substrates were scarcely affected. These results suggest the significance of electrostatic interaction in the lysis of lysozyme. Relatively limited loss of activity induced by modification of the 62nd residue, which is thought to participate directly in the binding of the substrate at subsite C, is discussed on the basis of the similarity of side chain structure in tryptophan and kynurenine.

We examined baroreflex function and plasma angiotensin II (Ang II) before and after the treatment with an angiotensin converting enzyme inhibitor (ACEI) in eight inpatients with essential hypertension (EHT). Baroreflex sensitivity (BS), expressed as a slope of linear relationship between %-changes in mean blood pressure (BP) and those in plasma concentration of norepinephrine (pNE), was greater during BP reduction by sodium nitroprusside (SNP) than during BP elevation by phenylephrine (PE). Enalapril treatment for 7 days reduced BP without a significant change in heart rate and pNE. It also increased the BS in two cases during SNP infusion and in four cases during PE infusion. Ang II was not significantly reduced after enalapril, while plasma ACE activity was suppressed by about 80% and plasma renin activity (PRA) was elevated. The changes in BS did not correlate with the changes in Ang II. The shift of barofunction curve with an enhancement of BS by enalapril therapy might not be attributed solely to the interaction between circulating Ang II and central baroreflex mechanisms.

A long-term prognosis was studied in 69 patients with malignant hypertension, followed for an average of 56 months. Overall survival rate was 90% for a 5-year period, although the prognosis was different between two major underlying diseases, namely the 5-year survival was 79% for 33 essential hypertension (EHT) and 100% for 26 chronic glomerulonephritis (CGN); the difference is significant (p less than 0.01). In contrast, the 5-year rate for renal survival, defined as the probability of surviving without hemodialysis, was 37% in all cases. However, there was significant difference in the renal survival between EHT (60% for a 5-year period) and CGN (4% for a 18-month period). Multivariate analyses of the Cox's proportional hazards model revealed that the long-term change in renal function was different between the two groups, namely more rapid deterioration in the CGN group. These results indicate that a long-term prognosis of malignant hypertension is influenced by the underlying diseases and hemodialysis besides antihypertensive treatment may increase survival in malignant hypertension associated with severely damaged renal function.

The acute transplantation of a normal kidney into a recipient rat with Goldblatt one-kidney, one clip hypertension (1K1C) results in a blood pressure (BP) fall toward but not below normal levels within 1 hour. Removal of the clip in a 1K1C hypertensive rat also normalizes the BP rapidly. These changes are not mediated by external fluid loss and occur after indomethacin pretreatment, but are associated with a fall in cardiac output. The mechanism of release of a depressor secretion from the kidney transplant appears to be under barostatic control. Thus, transplanting a kidney into a hypertensive recipient caused a prompt BP decline, whereas transplanting an SHR kidney into a hypertensive recipient did not lower the BP. The prompt BP fall seen after unclipping also indicates that abrupt exposure of the kidney to a high perfusion pressure initiates the release of some depressor agent. When the recipient rat was made hypertensive by injecting renin, the kidney transplant did not lower the BP. When angiotensin in subpressor dose was infused into the renal artery of the kidney transplant, the BP of the recipient did not fall, whereas infusion of norepinephrine in equiconstrictor doses did not prevent the depressor response. These experiments suggest that, in addition to a barostatic stimulus for depressor release, angiotensin acts as a specific inhibitor.

Two patients with malignant arterial emboli, one from a renal cell carcinoma and the other from a squamous cell carcinoma of the trachea, are described. Both patients had typical radiographic features of emboli on angiography. The origin of such arterial emboli is most probably a chest metastasis involving a pulmonary vein.