Somatostatin is a tetradecapeptide which was isolated whilst seeking the hypothetical gro wth hormone releasing hormone (GH-RH) in the crude extract of ovine hypoth alami. Since the isolation of somatostatin, the understanding of neural regulation of growth hormone secretion has been greatly facilitated.
Somatostatin in the pituitary stalk median eminence region (SME) is mainly located in axons or nerve terminals (synaptosomes) originating in other regions of the brain; preoptic region. The release of immunoreactive somatostatin from the isolated synaptosomes of hypothala-mic origin was stimulated by high (K⁺) and dopamine. The former effect was completely abolished by the removal of Ca⁺⁺from the media. Immunohistochemical observations revealed the existence of somatostatin and dopamine nerve terminals in a close proximity to the portal vessels of SME. These findings suggest that transsynaptic influence of dopamine on the release of somatostatin into the portal vessels.
When plasma GH levels were observed in intact rats provided with chronic indwelling right atrial cannulae under undisturbed conditions, they showed episodic secretory surge occurring at 3-4 h. The administration of specific anti-serum to somatostatin (A-SS) which acts to neutralize endogenous somatostatin led to elevations of both peak and trough GH levels. The result suggests that somatostatin exerts inhibitory influence on GH secretion and also, episodic GH secretion is mediated by a factor other than somatostatin. The latter presumably represents the action of still uncharacterized GH-RH. Episodic GH secretions were observed in rats performed either anterior or complete hypothalamic deafferentation. Thus, the neural mechanism responsible for generation of episodic GH secretion resides within the medial basal hypothalamus (MBH).
Various brain monoamines have been recognized to modulate GH secretion.These agents are considered to act through the central nervous system which ultimately modulate either somatostatin or GH-RH release. The administration of chlorpromazine (CPZ), an antagonist of brain, monoamines, inhibited episodic GH secretion acting through MBH via a factor other than somatostatin. The findings suggest that brain monoamines play important roles in the generation of episodic GH secretion.
A-SS induced elevations of plasma GH levels requires MBH, particularly hypothalamic ventromedial-arcuate nuclei complex. Since this complex does not send somatostatin to SME, elevations of plasma GH levels after A-SS injection appear to reflect the activity of GH-RH. Preliminary results suggest that dopaminergic mechanism was involved in A-SS induced plasma GH elevation. In addition, somatostatin plays a role in autoregulation of GH secretion.
In summary, A-SS offers a useful tool to investigate the role of somatostatin in the regulation of GH secretion. It is now clear that somatostatin is unlikely to be the sole regulator of GH.

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In the Japanese fetuses (30 specimens) and adults (23 specimens), the arteries in the region of the head and neck were macroscopically investigated. The arteries were injected with synthetic latex rubber through the thoracic aorta.With this method, the origin, course and branching pattern of the arteries were clarified in the portion.
The observations are as follows:
(1) The aortic isthmus was distinctly discernible immediately above the opening of the ductus arteriosus of all the 30 fetuses.The branching patterns (Adachi) of the aortic arch were classified into the followings: A type: 83.3%, B type: 10.0% and C type: 6.7%.
(2) It was found that in both the subclavian and vertebral arteries of the 30 fetuses the one on the left side was longer in diameter than the one on the right side.
(3) The level of the bifurcating part of the common carotid artery was statistically (fetus: 63.3%, adult: 73.3%) higher on the left side than on the right side.
(4) The length and diameter of the external carotid artery increased at both the left and right sides in proportion to the ages of the fetuses.In the external carotid artery of the persons of advanced age, meandering and zigzagging were distinctly observed.
(5) As for the diameters of the branches of the external carotid artery, the maxillar artery was the thickest and the ascending pharyngeal artery was the thinnest.All the other branches were about the same in diameter.
(6) There was no significant difference between the fetuses and the adults in the levels of the origin of the branches from the external carotid artery.
(7) The patterns of divergence of the branching arteries from the external carotid artery were classified into 5 types. I and IIA types were frequently observed.The other types were rare.
I type: 48.3%(fetus), 54.4%(adult)
II A type: 28.3%(fetus), 32.6%(adult)
(8) The common trunk of the branches of the external carotid artery was: thyro-lingual trunk (fetus: 1.7%, adult: 2.2%), linguo-facial trunk (fetus: 31.7%, adult: 15.2%), thyro-linguo-facial trunk (adult: 2.2%), and occipito-auricular trunk (fetus: 5.0%, adult: 17.4%).

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In Japanese fetuses (30 cases) and adults (57 cases), the brachiocephalic vein and its venous roots were macroscopically observed. Synthetic latex rubber was injected into the veins of the fetuses through the superior vena cava. The observations were as follows:
I. The brachiocephalic veins
(1) The projectional position of the union of the brachiocephalic veins existed in the posterior position of the first sterno-costal joint in 70.0% of the fetuses.
(2) In 83.3% of the fetuses, the angles formed by the right and the left brachiocephalic veins varied from 91 to 110 degrees, which were rather obtuse compared with those of the adults.
(3) The left brachiocephalic vein was longer than the right one in all the fetal cases, and in 66.7% of them the left one was 1.6-2.0 times longer.
(4) The levels of the right and left venous angles were as follows: the left angles were higher than the right in 26.7% of the fetuses parallel in 40.0%, and lower in 33.3%, and in the adults, 38.6%, 35.1%, and 26.3%, respectively.
II. The venous roots
(1) The right internal thoracic veins flow into the anterior wall of the union part of the brachiocephalic veins in more than 80% of both the fetal and adult cases and the left internal thoracic veins flow in most cases into the inferior wall of the left brachiocephalic veins.
(2) Most of the inferior thyroid veins flow into the superior wall of the left brachiocepahlic vein or into the union part of the right and left brachiocephalic veins, in both the fetuses and adults. They have anastomosis with thymic veins in 90% of the cases.
(3) The thymic veins mostly flow into the inferior or anterior wall of the left brachiocephalic vein in both the fetuses and adults.
(4) Most of the right and left vertebral veins flow respectively into the right and left posterior wall of the venous angles.

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For the purpose of studying on the influence of hypophysectomy to the immunological response of the rat, 21 days old female Wistar strain were divided into two groups, hypophysectomized and sham operated rats. The humoral antibody producing activity and the immune response of splenic and lymph node lymphocytes in both groups of rats were comparatively studied and the following results were obtained.
(1) The increasing curve of body weight in hypohysectomized rat was significantly suppressed and the growth was more retarded in comparison with that of sham operated rat. The body weight of the rat at the time of operation was about 40g, and that at 9 week after hypophysectomy was less than 100g.
(2) The hemagglutinin titers in the serum of the rat immunized with SRBC at 30-45 day after hypophysectomy were 8 times higher than that in the serum of sham operated rat.
(3) The number of plaque forming lymphocytes in the hypophysectomized rat immunized with SRBC at 20-45 day after operation was remarkably higher than that of lymphocytes in the sham operated rat.
(4) The λ-globulin levels in the serum of hypophysectomized rat seemed to be slightly higher than that in the serum of sham operated rat through this study for 45 days.
(5) The mitogenic (LPS, Con A) proliferation of the splenic and lymph node lymphocytes in both groups of rats was studied with ⁸H-thymidine incorporation method. The mitogenic (LPS) proliferation of the lymphocytes of the hypophysectomized rat at 12-20 day after hypophysectomy was revealed to be significantly accelerated in comparison with that before operation or at 21-20 day after operation in sham operated rat.
(6) From the patho-histological point of view, pyronine-stained cells in lymph node in both groups were observed at 5-20 day after installation of hypophysectomy, however, the finding was observed in the cells of sham operated rats to a lesser extent.

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The intravenous hyperalimentation (IVH) has found wide clinical applications in the case of the patients who can not be fed orally due to various causes.But IVH is not without side effects.One of them is the fat infiltration in the liver. The present experiments have been attempted to shed some lights on the genesis of this side effect, as well as its therapy.
The Wistar rats weighing about 200 g were divided into 9 groups according to the contents of the nutrients with which the rats were fed.The contents of the nutrients are as follows.
(I) commercially prepared rat food (control)
(II) low calorie electrolyte solution (administered intravenously)
(III) 50% glucose solution (IVH)
(IV) 12% amino acid solution (IVH)
(V) 19.5% glucose and 2.7% amino acid solution, 30-70 cal/kg daily (IVH)
(VI) 24.9% glucose and 3.2% amino acid solution, 200-250 cal/kg daily (IVH)
(VII) 33.1% glucose and 4.5% amino acid solution, 400-450 cal/kg daily (IVH)
(VM) 26.5% glucose and 4.2% amino acid solution with 1.2% fat emulsion, 200-250 cal/kg daily (IVH)
(IX) the solution having the same contents as in V111, but administered 400-450 cal/kg daily (IVH)
The IVH had been carried out for 7 days and then the liver of each rat was histologically examined with light and electron microscopes. The following results were therewith obtained.(1) A remarkable fat infiltration was found in Group X, VI and Vll. It was more pronounced in Group IX. The fat infiltration first occurred in the marginal zone of the hepatic lobules, and then spread to their central zone.(2) The giant droplets were discovered with the electron microscope, but no visible fat infiltration with the light microscope.(3) Swelling and rarefaction of the cytoplasm were observed in the liver cells of group V.(4) No conspicuous changes were found in Group WI.(5) Cirrhosis was not recognized in any groups.
In addition, the experiments were performed in order to find out when the fat infiltration began to occur and whether or not it was reversible.A careful histological study of the earlier stages revealed that the fat infiltration began within 24 hours after the initiation of IVH with a high glucose content. On the other hand, the rat which had been subjected to IVH with a high glucose content which should have caused the fat infiltration, did not exhibit the fat infiltration in its liver, if later fed with a balanced diet for 7 to 28 days.
The above results suggest that the fat infiltration of the liver was caused mainly by the overload of glucose in the earlier stage and by the imbalance of amino acid in the later stage. Consequently, it is expected that IVH consisting of glucose, amino acid and fat emlusion in a balanced proportion should cause no fat infiltration in the liver.

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The author has made an experimental pathological investigation on the cellular injury of the severe thermal burn in the central nervous system.
The results obtained are as follows:
(1) The cellular injury induced by the severe thermal burn in the central nerous system in early stage remained in slight to moderate degree. However, 12to72hours after recieving thermal burns, striking alteration of the blood brain barrier was noted.The changes were consisted of endothelial cell swelling, slight swelling and fragmentation of the basal lamina and pen-vascular edema. Occasional presence of lipid droplets was also noted in the pen-vascular region.
The vascular clearance study with fesin perfusion disclosed the increased permeability.Namely in the control group, the visualization of the fesin was rather localized in the endothelial cells of the capillary vessels, the visualization of the particles was rather extended to the pen-vascular spaces and astrocytic processess.
Degeneration of the myelin sheath was slightly observed, however, the change remained to a lesser extent and the basic changes involved in this stage appeared to be derived of acute circulatory disturbance.
(2) The previously mentioned changes were subsiding gradually 72 hours after recieving thermal burns.
The pen-vascular edema was also subsiding, however, contrary, reactive proliferation of the microglia, destruction of the oligodenroglia and degeneration of the astrocytes were prominent. The atrophy and loss of nerve cells in accordance with the changes of the glial elements as mentioned previously. The central chrornatolysis of the nerve cells also forms conspicous feature.
More importantly the author inclines to draw a conclusion that the clinically observed thermal burn induced encephalopathy is consisted of acute circulatory failure and cellular injury to the central nevous system.
Based on this observation, the author also would like to call an attention for protecting the cellular injury which would subsequently resulting after causation of acute circulatory failure in the thermal burun.
In this communication, the causative factors of the thermal burn encephalopathy have been extensively studied ultrastructually and experimental basis for therapeutic efforts of this condition is fully augmented.

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The inferelatia of the fecal E. coli in the mother and child attracts much attention of the investigators and the importance of this interaction has been documented in the literature.However, investigated cases are rather limited and the detailed patho-physiological significance should await further elucidation in future. In this viewpoint the author has isolated the E. coli from the fecal materials of mother and newborn infant chronologically and subtyped serologically. Moreover, concerning infection with reference to the mother-child relationship, circumstantial factors and infulence of the E. coli on mother and child have been investigated in this study.
The study also has attempted to elucidate the mechanism how the E. coli settle in human intestine as normal flora.
(1) The E. coli in newborn infant was isolated within 24 hours as the rate of 9.2%, 40.8% within 48 hours, and 61.8% within 72 hours.
(2) Related to the relationship between delivery time and detection rate of E. coli in newborn intestine, it is very interesting to note that majority of the cases of prolonged delivery time beyond 18 hours disclosed detection of the E. coli within 48 hours.
Contrary, in cases which showed delivery time within 18 hours, only detection rate of 35.8% was noted.
(3) No significant correlation was observed in detection rate of E. coli and time interval of rupture of membrane and delivery of the babies.
(4) Of 561 strains of E. coli separated from mothers and children, 194 strains (34.1%) could be identified serologically.
(5) Serological typing disclosed 14 subtypes, namely, 0-1, 2, 18, 6, 13, 4, 8, 14, 15, 25, 12, 21, 23 and 36.
(6) Out of 54 cases, 8 cases disclosed identical subtyped E. coli between the mother and child.
(7) Among newborns admitted at about the same time, 24 cases (44.4%) of 54 showedidenticalserum types.
Based on these observations, it is concluded that the highly probable presence of horizontal dissemination of the E. coli in newborn infants in virtue of circumstantial factors, although vertical dissemination in a mode of the mother to child relation should be present to a lesser extent.

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By means of “IV ¹³³Xe method”, the utero-placental blood flow (UPBF) was measured in 38 cases in the 28 th to the 38 th week of pregnancy.In all cases the placental villi were detected to have been imbedded in the anterior wall of the uterus with the ultrasound Bscan. The scintillation detector was placed on the abdominal wall overlying this portion.From the recorded ¹³³Xe wash-out curve, quick and slow components were obtained. The quick component reflected the fractional removal of the tracer from the intervillous blood pool while the slow component the removal from the myometrium. UPBF (_pF) was calculated by putting the value of the half life period (_pT½) obtained from the quick component into the equation: _pF=100×0.69/_pT½ml/min/100g. On the other hand, the myometrial blood flow calculated by putting the value of the half life period (_mT½) derived from the slow component into the equation: _mF=70×0.69×_mT½ml/min/100g. The “IV ¹³³Xe method” is relatively simple and safe in humans. The radiation dose of 0.6 mCi of ¹³³Xe is less than 1 mrad. Employing the ultrasound Bscan, the placenta was first located, and then the fetal biparietal diameter (BP-d) and the placental thickness were measured. The placental functions (urinary E₃ and HPL) were measured on the day of the ¹³³Xe clearance measurements. The correlations between UPBF and the fetal BP-d, the placental thickness and the size of the newborn were studied, and the following results were obtained.
(1) UPBF in the 28 th to the 31 St gestational week was 68.4ml/min/100g in average whereas in the 32 nd to the 35 th 68.7, and in the 36 th to the 39 th 66.0.Thus there were no significant differences according to the differences in the gestational week.The experience of the parity did not influence the results.
(2) The myometrial blood flow in the 28 th to the 31 th gestational week was 3.78ml/mini 100g in average while in the 32 nd to the 35 th 4.39, and in the 36 th to the 39 th 4.55.Thus the differences in the gestational week did not affect the blood flow, nor did the experience of the parity.
(3) There were no significant correlations between E₃ or HPL and UPBF.
(4) No significant correlation was found between UPBF and the fetal BP-d.The thickness of the placenta, on the other hand, was significantly correlated with UPBF in the cases with the history of parities in all gestational weeks studied, but only in the 36 th to the 39 th gestational week in the cases without the history of parities.
(5) The weight, the height, the circumference of the chest and the Bp-d of the newborn were not significantly correlated with UPBF.
(6) The placental weight, area and ratio were measured after the delivery.These values were not significantly correlated with UPBF.
(7) The UPBF in a patient with the toxemia of pregnancy, Hashimoto disease, the scleroderma was measured in the 32nd gestational week. The value was lower than the rejection limit of the value of the normal subject. Soon after the measurement, the patient developed the fetal distress, resulting in a still-born. This case suggests a possible clinical application of the measurement of UPBF.

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In has been well recongnized that the uterine endometrium is the tissue which is very sensitively responding to the sex hormone stimulation and extensive search for the endmetrial alteration in various menstrual cycle and gestational stage may faciliate the clarification of the causation of abortion or malformation.
In this connection, the author has investigated the ultrastructural changes of the endometrium in various menstrual cycle and early stage of gestation.
Five cases of adult female were subjected for this investigation. Determination of the various menstrual cycle was made in virtue of the basal body temperture measurement.
The results obtained were as follows:
(1) The secretory function is activated in accordance with proliferative, ovulatory, secretory phases and implanted site of the decidua.The parietal decidua which is apart from the implanted site disclosed the secretory effect to a lesser extent than the basal decidua.
In this connection, decrease of free ribosomes, swelling of the mitochondria and increase of rough-surfaced endoplasmic reticulum consist most striking ultrastructural features.
(2) The normal endometrial lining layer is lined with clear and dark cells.The dark cells may possess striking increase of cellular transport mechanism and also disclose intense stainability to the ruthenium red stain.The ultrastructural study of the dark cells also reveals marked increase of the rough-surfaced endoplasmic reticulum and Golgi complexes ans secretory granules. The presence of the abundant secretory granules in this cell may reflect a possibility that the cells possess pronounced secretory function in comparison with clear cell.
(3) The secretory granules in secretory phase are composing of rather small rounded granules of variable sizes and variable stain intensity.The finding may suggest a possibility that the cells are forming various precursers of the granules which are eventually being secreted in matured form.The granules are essentially devoid of the staining property in conventional electron stain and appear to be basically composed of lipid, however, in view point that the granules also disclose PAM stainability which suggest that the granules also contain mucopolysaccharide as one of the main constituents.Incidentally the holocrine pattern secretion is also unfrequently encountered.
(4) The thickening and stain intensity to the ruthenium red stain are observed in order of proliferative, ovulatory and secretory phases, measuring approximately 200Å to 300Å in thickeness in the uterine glandular epithelum.
The distribution of the coarse granularity to the lining of the glandular structure of the uterine endometrium suggests the marked negative electron charge.

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