Under a scanning electron microscope, the lymphatic vessels of the rat stomach and the rabbit small intestine were observed by a corrosion casting technique. The structures thus revealed were compared with those embedded in Epon by a light microscope. On the mucosal layer of the rat stomach, the lymphatic casts showed various structures, i. e., fusiform casts from the subepithelial lymphatics, a basket-shaped structure from the interglandular lymphatics and a horizontal network of leaf-like structures from the subglandular lymphatics. These casts also showed several nuclear depressions about 10 μ in diameter, a number of constrictions, and numerous small holes representing reticular or collagen fibers interrupting the Mercox filling.
The submucosal lymphatic casts of the rat stomach showed irregular tubular or flat shapes about 20-40 μ in diameter, nuclear depressions about 15 μ in their long diameter with sawtoothed figures around them, bead-like swellings, and occasional V-shaped incisura on parts of the columns. Similar findings were also observed in the submucosal layer of the rabbit small intestine. On the mucosal layer of the rabbit small intestine, the central lacteal casts showed peculiar figures, i. e., a dome-shaped structure about 70-80 μ in diameter at the topmost portion, swelling to about 100-200 μ in diameter in the middle, and an evident constriction to 30-60 μ in diameter at the bottom. Some of the morphological characteristics of the central lacteal at any site of the small intestine were clarified by this study: a) in the duodenum, three or four central lacteals within one villus formed pedunclar anastomoses branching from about half way up the lamina propria, b) in the jejunum, one or two lacteals within a villus had swellings just above the bottom constriction, and c) in the ileum, each villus contained only one lacteal with a swelling in a higher position.

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Antibody-dependent cell-mediated cytotoxicity (ADCC) of human peripheral leukocytes was investigated using ⁵¹Cr-labelled sheep red blood cells (SRBC) sensitized with rabbit anit-SRBC antibody as target cells. ADCC (lysis of target cells without erythrophagocytosis) was mediated by the lymphocytes. On the other hand, phagocytes including monocytes and granulocytes showed antibody-dependent erythrophagocytosis (ADEP). ADCC of the lymphocytes was augumented by the enrichment of Fc-receptor bearing or Nylon-wool column passing cells. Phagocytes showed rapid ADEP, and granulocytes released ⁵¹Cr-radioactivity originating from target cells into the culture medium in a short time, whereas the monocytes released little radioactivity during the incubation period. The monocytes inhibited ADCC of the lymphocytes competitivelly through ADEP, since decreased ADCC activity of monocyte-contaminated crude lymphocyte fraction was recovered by elimination of contaminating monocytes. Antibody-independent erythrophagocytosis of SRBC was mediated by monocytes, but not by granulocytes. Both ADCC of lymphocytes and ADEP of phagocytes were dependent on IgG-antibody, IgM-antibody did not participate in these phenomena. ADEP of monocytes was detected at 10^-2-10^-6 dilution of IgG-antibody fraction (original hemmagglutination titer;×1600), and ADCC of lymphocytes and ADEP of granulocytes were detected at 10^-2-10^-4 and 10^-2-10^-3 dilution of this antibody fraction, respectively. Soluble cytotoxic factors were not released from lymphocytes, monocytes or granulocytes in this assay system, because no cytotoxic activity on ⁵¹Cr-labelled human erythrocytes used as an adjacent cell was demonstrated by any leukocyte fraction in the presence of antibody-coated SRBC.

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Antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent erythrophagocytosis (ADEP) of peripheral blood leukocytes in patients with Sjögren's syndrome (SjS) or rheumatoid arthritis (RA) were investigated using ⁵¹Cr-labelled sheep red blood cells as target cells. The Lymphocytes (phagocyte depleted fraction, PDF) in healthy controls showed higher ADCC activities (58.6±9.9%) than the phagocyte-contaminated crude lymphocyte fraction (CLF) (49.1±10.9%). There was no statistically significant difference between the ADCC activities of PDF in patients with SjS (55.9±13.5%) or RA (58.8±9.6%) and those in healthy controls, although decreased ADCC activity was observed in some patients with SjS. ADCC activities of CLF in patients with SjS (61.2±14.3%) or RA (59.3±6.9%) were significantly higher than those of CLF in healthy controls. Decreased ADEP activity of monocytes in CLF was demonstrated in patients with SjS (17.9±9.4%) compared with healthy controls (37.2±10.6%), and increased ADCC activity of CLF in patients with SjS was dependent on decreased ADEP activity of contaminating monocytes. Decreased ADEP activity of monocytes in patients with RA was also suggested by these results.
It was speculated that the decreased Fc-receptor function of peripheral blood monocytes, demonstrated in these patients, had originated from aberrant cell-mediated immunity in these diseases, since these Fc-receptor functions in patients with SjS did not correeate with the following conditions: associated diseases, erythrocyte sedimentation rate, titer of serum rheumatoid factor, lymphocyte count of peripheral blood, or treatment with anti-inflammatory drugs including prednisolone.

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X-radiation decreases the number of RBC in vivo and accelerates hemolysis in vitro, but the mechanism is still unclear. Taking the view that these phenomena are due to radical formation and active enzyme formation followed by accelerated peroxidation of cell membrane lipid and membrane structural changes we studied the morphological changes of RBC, changes in ion-partition, and the inhibitory effects of drugs. The results were as follows: 1) Hemolysis of human erythrocytes (RBC) was accelerated by x-radiation. The degree of such lysis was proportional to the degree of x-radiation. This lysis was inhibited markedly by the addition of cephalanthin. The inhibitory effect was dependent on the concentration. In high concentrations conversely acceleration occurred. 2) Soon after x-radiation and prior to hemolysis, human RBCs released K⁺ bringing about a decrease in the K⁺ partition. The time of this decrease paralleled the degree of x-radiation. The K⁺-partition decrease caused by x-radiation was inhibited by the addition of cephalanthin. 3) In parallel with the acceleration of erythrocyte membrane permeability by x-radiation, changes in RBC morphology were more likely, thus causing structural changes in the cell membrane. 4) Cephalanthin protects the RBC from its instability to x-radiation, and at certain concentrations it restores normal morphology to RBC that have an Echinocyte structure, but at high concentrations it makes RBC to assume a stomatocyte shape. 5) The above findings are discussed in terms of cell membrane injury mechanisms and the inhibitory effect of cephalanthin.

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The microcirculation of the rat adrenal gland was studied with a corrosion cast technique and a freeze-cracking method under scanning electron microscopy. 1) The adrenal arteries run in the surface of the adrenal gland, branch off into arterioles which finally form the subcapsular plexus. This plexus is a dense anastomosing network covering the surface of the adrenal gland. 2) The cortical capillaries arise from the subcapsular plexus, and run vertically towards the adrenal medulla. These capillaries have sinusoidal structures. 3) The cortical capillaries make up a honey-comb pattern in the outer glomerulosal zone and become dense and thick in the cortico-medillary border. 4) The medullary, cortical and looped arteries penetrate the subcapsular plexus and run vertically into the cortex. 5) Most medullary arteries have 1 to 3 branched which run back towards the surface to join in the subcapsular plexus. Hence the author termed these recurrent arteries. The medullary artery occasionally has a branch which runs to the medulla, but does not anastomose with the cortical capillary plexus. 6) The capillaries of the medullary artery are smaller, and the plexus which is made of these capillaries is more coarse than the cortical plexus. These plexes have a coarse anastomosis with cortical capillaries and then run into the medullary vein. 7) The medullary veins drain into one adrenal vein. The adrenal vein anastomoses with the subcapsular plexus in rats as well. 8) Similar results were observed in the freeze-cracked specimen. In addition, in the endothelium of the cracked cortex, many polymorphous fenestrations were observed which were analogous to liver sinusoidal fenestrations. 9) The shape and size of the fenestrations vary with the technique of making the specimen. The fenestrations were very small and uniform when the adrenal gland was not irrigated.

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With rats from which about 70% of the liver was previously removed, corrosion casts and specimens of freeze-cracking method were prepared from time to time after the operation. These specimens were used for scanning electron microscope observation. Ultra-thin sections were also prepared for transmission electron microscope observation to study regeneration of the sinusoid during regeneration of the liver. The results were compared with normal rat liver, and were as follows: Regenerative proliferation of the sinusoid after partial hepatectomy began about 12 hours after hepatectomy. First the space of Disse enlarged. This later becomes a sinusoid, so the author had designated it as a presinusoid space. The presinusoid spaces appear about 12 hours after hepatectomy, and can be observed up to about the third postoperative day. In the early stages, they are spherical, about 2-10 μ in diameter, and grow larger with lapse of time. Later they become larger than the sinusoid. Some have many bumps running parallel to the sinusoids, while others bind with the sinusoid to form bridges. They are located at the margin of the sinusoid facing one fixed direction. The sinusoid and the presinusoid space are separated by endothelial cells lying in between them. The other external wall is composed of liver cells. The number of microvilli of the liver cell surface is extremely small. This stage has been called the stage of the presinusoid space. In the presinusoid space, the liver cell surface which forms the exterior wall shows newly formed endothelial cells after cell division. These protrude and completely cover the inner surface. At the same time a neoplastic sinusoid forms by removing the endothelial cells there. The formation of the new sinusoid starts about 24 hours after partial hepatectomy and continues up to about the third postoperative day. This stage has been designated the sinusoid budding stage. The neoplastic sinusoid is at first closed at one end but later these neoplastic sinusoids fuse to form a new sinusoidal network. Such fusion commences about 48 hours after partial hepatectomy, and continues vigorously for about 3 postoperative days. This stage is called the fusion stage. The new sinusoidal network formed by the fusion of neoplastic sinusoids is irregular, and its surface is uneven, but with time, the arrangement and the surface contour become regular and smooth. The process is completed by about 14 postoperative days. This stage has been designated the completion stage.

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Electrocardiographic changes caused by electrical stimulation of individual cardiac sympathetic nerves were observed with Frank's corrected orthogonal lead system and Frank's vetorcardiogram. The effects of drugs on nervous stimulation and the electrocardiographic changes after the resection of the cardiac nerves were investigated in 45 closed chest dogs.
The following results were obtained: 1. The amplitude of the T wave decreased in Y lead and increased in Z lead in 20 out of 34 cases in which the right stellate ganglion [R. S. G. (A)] had been stimulated and in all cases in which the right recurrent cardiac nerve (R. Rec. C. N.) and the left ventromedial cervical cardiac nerve (L. V. M. C. N.) had been stimulated. Spatial maximum T vector displaced anteriorly and superiorly. The magnitude of spatial maximum T vector increased in all cases. 2. An increase in the amplitude of T waves in Y lead was seen in all cases in which the left stellate ganglion (L. S. G.), and the left ventrolateral cervical cardiac nerve (L. V. L. C. N.) had been stimulated, and in 14 out of 34 cases in which the right stellate ganglion [R. S. G. (B)] had been stimulated. The spatial maximum T vector was displaced inferiorly. The magnitude of the spatial maximum T vector increased in all cases. 3. The amplitude of the T wave increased in Y lead with simultaneous stimulation of both right and left stellate ganglia. The spatial maximum T vector was displaced inferiorly and the magnitude of the spatial maximum T vector increased in all cases. These electrocardiographic changes were similar to the changes which occurred with single L. S. G. stimulation. 4. Rotation of the T loop in the left saggital plane was clockwise in more than 80% of cases with R. S. G. stimulation. However, rotation of the T loop in left saggital plane was counter clockwise in more than 75-80% of cases with L. S. G. and simultaneous stimulation of both right and left stellate ganglia. These results suggest that right and left cardiac sympathetic nerves innervate different myocardial areas and affect the local myocardial action potentials to cause these electrocardiographic changes. 5. In more than 40% of cases with stimulation of left cardiac sympathetic nerves (L. S. G., L. V. L. C. N.). arrythmias such as A-V dissociation and A-V junctional rythm were recognized. In more than 90% of cases with stimulation of right cardiac sympathetic nerves (R. S. G., R. Rec. C. N.), marked increase of sinus rythm occurred. 6. These electrocardiographic changes resulting from nervous stimulation decreased or disappeared after the use of propranolol. These results suggest that these electrocardiographic changes were caused by β-effects of catecholamines. 7. The QT ratio corrected by the formula of Bazett increased in all cases of right and left cardiac sympathetic nervous stimulation. 8. Long term observations after right or left stellate ganglionectomy revealed no significant changes in electrocardiographic patterns and a tendency to decrease in the QT ratio corrected by the formula of Bazett.

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Persistent juvenile T wave patterns found in mass examination and in clinical cases were studied for the purpose of clarifying their significance. Persistent juvenile T wave patterns were classified into three types. Type I had negative T waves in lead V₁ only, Type II in lead V₁ and V₂ and Type III in V₁ to lead V₃ or V₄. During mass examinations, persistent juvenile T wave patterns were found in 243 cases (43.5%) of 558 male subjects. Of these, 15 (6.2%) were Type II, III. On the other hand they occurred in 547 (66.5%) of 823 female subjects. Of these, 86 (15.7%) were Type II, III. The incidence of each Type of persistent juvenile T wave pattern did not vary significantly with age, but Type II, III were relatively more frequent between 35 and 49 years of age. Persistnet juvenile T wave patterns were often positive in many cases in electrocardiograms (ECG) thaken from the same subjects 8 years after the first mass examination. Standard ECG's and Frank's system vectorcardiogram (VCG)'s were analysed in 116 clinical cases showing persistent juvenile T wave patterns. Transitional zone and electrical axis deviation in ECGs were almost normal in the persistent juvenile T wave pattern. The shape of the transverse T loop was mostly normal whereas the transverse QRS loop normally varied in shape. Clockwise rotation of the transverse T loop was observed in 15 of 116 clinical cases. The maximum magnitude of the T loop in VCG was significantly smaller in Type III than in Type I, II. Changes in the persistent juvenile T wave pattern on ECG and VCG were studied in 25 cases after administration of Propranolol. The negative T wave in ECG tended to become positive and the maximal T vector tended to become larger shifting towards anterior in VCG after administration of Propranolol. The persistent juvenile T wave pattern was observed more frequently in middle aged women and usually became normal after administration of Propranolol. These results suggest that increased sympathetic tone is one of the pathological mechanisms involoved in the persistent juvenile T wave pattern.

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Hemolytic anemia was associated with Rauscher leukemia. Anemia was observed slightly in the early stages of leukemia and developed progressively during the later stages. The mechanism of hemolytic anemia can be explained as being due to both intracorpuscular defects and extracorpuscular factors. The former, i. e., intracorpuscular defect, consists of intracorpuscular defects caused by direct effects of Rauscher leukemia virus on red blood cell and also “abnormal” erythrocytes which migrate into peripheral blood from the spleen. These “abnormal” erythrocytes were produced by the maturation of malignant erythoid cells induced by Rauscher leukemia virus. The latter, i. e., extracorpuscular factor, will be described part two of this article.

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Using Rauscher leukemia virus, changes in the reticuloendothelial phagocytic activity were studied by a carbon clearance method and a heat-damaged ⁵¹Cr-labelled red blood cell method. With the carbon clearance method, after virus infection, phagocytic activity was slightly increased in the early stages, but decreased gradually during later stages. With the ⁵¹Cr-labelled RBC method, in the early stages, phagocytic activity of liver and spleen was slightly increased and during the later stages accelerated markedly in the liver in contrast to supressed activity in the spleen. It was suggested that an early increase of phagocytic activity observed by both methods was a response to viral infection. Significantly accelerated phagocytic activity seen in the liver during later stages with the ⁵¹Cr method may have been related to the hemolytic anemia associated with Rauscher leukemia.

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Scanning electron microscope observations were conducted on cross-sections and bloodvessel casts of normal rat thymus. A comparative study was carried out with thymus crosssections prepared from rats injected with corticosteroid and from rats undergoing muscleembedding transplantation. The results were as follows: Cortical lymphocytes of normal rat thymus had fewer microvilli, while medullary lymphocytes had many. The network made by epithelial cells was smaller but that made by the medullary cells was larger. The cortexmedulla boundary was distinct on the cortical side and indistinct on the medullary side. The interior surface structures of the posterior capillary venules presented a variety of changes which enabled smooth wandering of the cells. There were also some lymphocytes penetrating through the vascular endothelium. With blood vessel casts cicatrization of the posterior capillary venules was characteristic. On the interior surface of the thymus cyst there were villous or cribriform structures.
In the cortex of the rat thymus injected with corticosteroid destruction of lymphocytes was marked, and in the medulla a decrease in the number of lymphocytes was the main change. In the rat thymus after muscle-embedding transplantation cortical lymphocytes appeared rounded and there were many ciliated cells.

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Differential hypothermia (D. H.) treatment (preservation of brain tumor at normothermia during generalized body hypothermia) for the treatment of human brain tumors requires the tumor to be heated throughly and maintained for the necessary time. The normal portion of brain has to be protected during and after the treatment. Microwave (MW) seemed the most suitable heating method, so its effects on the normal brain of dogs were studied.
During MW irradiation, the thermistor-probe showed higher temperatures erroneously. When the probe was covered by aluminium foil, the measurement error was less than 0.2°C as long as the probe was in the brain. This method sufficiently heated the brain under generalized hypothermia down to 2 cm in depth from the surface. The highest temperature was recorded between 0.5 cm and 1 cm in depth and was easily controlled by the output of MW. On the other hand, aluminium foil blocked MW irradiation completely, therefore the irradiation field possibly protected the normal portion.
To study the safety limits of heating by MW irradiation, two groups of rabbits maintained at different temperatures (37°C and 40°C) were prepared. Following D. H. treatment for 5 hours in each group, the rabbit brains were examined histologically. The results showed minimal brain damage by MW irradiation in the 37°C group. In the 40°C group, heat necrosis was constantly observed as well as stagnation of vessels and perivascular cuffing of round cells.
From these findings, it was concluded that MW was useful as a heating method during D. H. treatment. The safety limit of heating was up to normothermia.

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Differential hypothermia (D. H.) treatment was performed on normal rabbit brains and the associated changes in cerebral metabolism were observed in series. Under generalized body hypothermia (rectal temperature; 23°C), a portion of normal brain was maintained at normothermia (37±1°C) by heating with microwave irradiation (2.45GHz). Brain tissues were sampled as follows; before treatment, at the beginning, 3, 6 and 10 hours later, and finally 12 and 36 hours after completion of the 10 hour-treatment. Five rabbits were studied in each group to be 35 as a total sum. In each rabbit, two samples; one from the normothermic portion and one from the hypothermic portion, were obtained. By using enzymatic analysis, six glycolytic metabolites (glucose, glucose-6-phosphate, fructose-1, 6-diphosphate, dihydroxyacetone phosphate, pyruvate, lactate) and three adenine nucleotides (ATP, ADP, AMP) were investigated quantitatively. From these results, the ratio of lactate and pyruvate (L/P ratio) and energy charge potential (ECP) were calculated.
Before the treatment, the L/P ratio was 26.4 and ECP was 0.921. Up to 6 hours after the beginning, the metabolic status in the normothermic portion was relatively higher than the hypothermic portion. Namely, L/P ratio and ECP in the normothermic portion reached 27.6 and 0.953 respectively. On the completion of the 10 hour-treatment, however, glucose decreased considerably. While G6P increased markedly associated with a L/P ratio of 47.5. Similarly ATP was decreased, while ADP and AMP were increased, therefore ECP decreased to 0.873. These data indicated tissue hypoxia. On the other hand, 36 hours after the treatment, the L/P ratio recovered completely to 18.7, ECP also recovered to 0.901.
These results indicated that metabolism in the normothermic portion was smooth up to 6 hours duration of treatment, although it was constantly higher than the hypothermic portion. On the completion of the 10 hour-treatment, increase of glycolysis by tissue hypoxia and failure of energy metabolism were observed. However, these changes were considered still reversible because the results obtained after the treatment indicated reasonable recovery. Therefore it was suggested that 10 hour-differential hypothermia treatment on the normal rabbit brains was safe from a viewpoint of glycolytic and energy metabolism.

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The effects of coronary vasoactive drugs on coronary collateral were studied in anesthetized open-chest dogs. The circumflex coronary artery was gradually occluded by an aneroid constrictor. Four to eight weeks later, retrograde coronary blood flow from the peripheral coronary artery and other parameters were studied. The results were as follows.
1) Propranolol (0.2 mg/kg) decreased myocardial oxygen consumption represented as pressure rate product and increased peripheral coronary vascular resistance slightly. Retrograde coronary blood flow decreased significantly. The effect of propranolol was to improve the imbalance between myocardial oxygen demand and supply.
2) Nitroglycerin (20 μg/kg) caused a reduction in preload and myocardial oxygen consumption. Retrograde coronary blood flow did not increase.
3) Diltiazem (0.15 mg/kg) decreased myocardial oxygen consumption. Retrograde coronary blood flow was not significantly changed.
4) Isoproterenol (0.2 μg/kg) aggravated the myocardial oxygen demand-supply relationship.
5) There was a significant reduction in the regional myocardial shortening in the ischemic area compared with the control area. The response of regional myocardial shortening to the drugs in the ischemic area, however, was similar to that in the control area.

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The effects of six fixatives (Carnoy, Allen, Gendre, Rossman, Glutaraldehyde and Periodic acid-formalin) on the distribution of glycogen of the liver were studied by light and electron microscope.
In tissue fixed with Carnoy, Allen, Gendre and Rossman, liver cells showed an alcohol flight phenomenon and chess board pattern was observed in the center of the tissue. The results obtained from freeze-drying method, that is, the alcohol flight phenomenon was an artifact, but the chess board pattern was not. In tissue fixed with glutaraldehyde and periodic acid-formalin, the alcohol flight phenomenon was rarely observed but the chess board pattern was clearly recognized.
To study the effect of the temperature of fixatives on the changes in glycogen distribution, liver was fixed with glutaraldehyde and periodic acid-formalin at various temperatures. Good results were obtained with periodic acid-formalin under 20°C or with glutaraldehyde under 4°C.
Electron microscopy showed that five fixatives (except glutaraldehyde) caused cell disruption and fine ultrastructure was not observed. Glycogen was observed as β and α particles with glutaraldehyde fixation. The effect of pH of glutaraldehyde solution on glycogen distribution was not discernible.
These results showed that fixation with glutaraldehyde was the best method to study glycogen particles by both light and electron microscope.

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Specific granules of heart atrial muscle obtained from mammals (mouse, rat, rabbit, dog, pig, ox and monkey), aves (chicken), reptiles (Geoclemmys), amphibia (Rana), pisces (carp, goldfish and shark) and cyclostomata (Entosphenus) were investigated by electron microscope and the following results were obtained.
The mean diameter of the specific granules was large in rat (315 nm) and mouse (283 nm), medium in rabbit (260 nm) and pig (210 nm) and small in dog and ox (170 nm) and monkey (175 nm) among mammals. The core of these granules was electron-translucent in rat and mouse and electron-dense in rabbit. The atria of rat and mouse had a large number of granules while that of monkey showed a fairly large number of granules. The dog showed a small number of granules and the granules of ungulate (pig and ox) were sparse.
Granules in vertebrates other than mammals were relatively smaller than in mammals. The mean diameter was 144 nm in chicken, 175 nm in Geoclemmys, 150 nm in Rana and carp and 168 nm in Entosphenus. The atria of Geoclemmys and Rana had a large number of granules while that of Entosphenus also had a fairly large number of granules. Shark only showed a small number of granules and the granules of chicken, carp and goldfish were sparse.
Electron microscopic study of specific granules in rat heart atrial muscle showed that there were two types of granules. One (Type I) had a homogenous and electron-dense core and the other (Type II) was electron-translucent and consisted of small granular materials. Both were enclosed by a limiting membrane. Type II were distributed near the Golgi apparatus present at the perinuclear area of the muscle cell while Type I were widely distributed in sarcoplasm at the perinuclear area, between myofibrils and beneath the cell membrane of the cell.
From the results, the process of the formation, maturation and release of specific granules of heart atrial muscle was discussed.

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The fine distribution of blood vessels of the esophagus of rat, rabbit, and man was studied by the corrosion cast method. The vascular casts were made by injecting Mercox into the artery of the esophagus and removing the tissue with 20% KOH. These were observed under a scanning electron microscope. In addition, the healing process of an anastomosing part in the lower portion of the esophagus of rat was observed by the same method. In each layer of the esophagus particular microvascular patterns were observed as follows: 1) At the tunics adventitia thin capillaries formed a coarse meshwork, and large vessels ran through this capillary mesh in places.
Capillary nets of muscle layers were thick and dense. These were composed of two layers which corresponded to the longitudinal and circular muscle layers. 2) Arteries of the submucosa ran longitudinally, and after branching or anastomosing, formed fine networks in the submucous layer. Numerous veins which pierced the muscularis mucosa from the lamina propria increased in diameter and also ran longitudinally in the submucous layer. They were connected by numerous cross anastomoses and some perforated the muscle coats of the esophagus to reach the outer surface.
These vessels in the submucous layer constituted the submucous plexus. 3) At the lamina propria small arteries coming from the submucosa branched out and finally divided into capillaries. These capillaries formed a coarse and slightly elongated polygonal meshwork. In man the capillary mesh of the lamina propria projected into the lumen of the esophagus and showed a similar appearance to the vascular pattern of the villi of the small intestine. Small veins receiving their blood supply from the capillary mesh and connecting with numerous cross anastomoses ran longitudinally in the lamina propria and finally joined into the veins of the submucosa. 4) Microvascular patterns at each stage of the healing of an anastomosis of the esophagus were observed as follows. i) 3rd day postoperation: Vascular casts were lacking at the site of anastomosis. By observation with high magnification the buds of regenerating vessels were found at the wall of large vessels of the anastomosing site. ii) 5th day postoperation: The regenerating vessels had elongated, and anastomosis with vessels of the opposite side had begun. iii) 7th day postoperation: Revascularisation at the anastomosing part was almost completed. The microvascular pattern of each layer still remained irregular and showed incompletion of the regeneration of blood vessels. iv) 14th day postoperation: As the constitution of blood vessels of each layer of the anastomosing part showed almost normal appearance it was assumed that the healing of an anastomosis of the esophagus had been mostly completed by this stage.

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In this paper, the author describes the determination of metabolites in the urine of shipyard workers exposed to thinner containing toluene and xylenes. Urine was taken from 4 healthy workers working at the same place, in the morning (a. m. 8:00), at noon (p. m. 0:00) and in the afternoon (p. m. 5:00), 3 times in a day for 5 consecutive days. Urinary metabolites, i. e., m-methylhippuric acid, p-methylhippuric acid and hippuric acid, were determined by high-performance liquid chromatography. The results were: 1. m-Methylhippuric acid, p-methylhippuric acid and hippuric acid in the urine of painting workers could be determined by high-performance liquid chromatography following extraction and benzoxylation. The stationary phase used in this experiment was silica gel and the mobile phase was a mixture of n-hexane and chloroform. 2. Concentrations of urinary m- and p-methylhippuric acids and hippuric acid were lowest just before, and generally highest just after, work. These results suggest that the workers were inhaling the thinner vapor even though wearing gas masks. 3. Peaks of m- and p-methylhippuric acids occurred in the chromatogram of workers' urine collected before work in the morning, although there were no peaks in the chromatogram of normal urine. This indicates that m- and p-xylenes may still remain in the workers' bodies.

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The purpose of this study is to investigate differences in excretion of toluene and m-xylene. After intraperitoneal injection of toluene or m-xylene (5 mmole per kg body weight) to Wistar female rats, urine and expired air were collected regularly. The concentrations of toluene and m-xylene in expired air were determined spectrophotometrically. Their urinary metabolites hippuric acid and m-methylhippuric acid were measured by high-performance liquid chromatography. The results were: 1. The excretion rates in expired air for 10 hours after the administration of toluene and m-xylene were 37.7% and 13.1% respectively. After the injection of toluene, the excretion rate per hour of the vapor in expired air increased rapidly, and reached a maximum (6.1%) in 2 hours, then decreased in a half-life of 4.87 hours. The maximum excretion rate of m-xylene per hour was 1.6% in 3 or 4 hours; thereafter, the excretion rate decreased more slowly than in the case of toluene. 2. The total excretion rate in urine for 48 hours after administration was 29.0% for toluene and 43.5% for m-xylene. Urinary excretion of m-xylene is apparently higher than that of toluene, in contrast to expiratory excretion. Following the administration of toluene, about 14% had been eliminated as hippuric acid in the 0-10 and 10-24 hours' urine. The concentration of hippuric acid had returned to normal in the 24-48 hours' urine. m-Methylhippuric acid in the 0-10 hours' urine was 13.7% of m-xylene; in the 10-24 hours' urine it was 22.3%; moreover, 7.5% was found even in the 24-48 hours' urine. From these results, it is estimated that the velocity of urinary excretion of m-xylene is less than that of toluene. 3. The total excretion rate of toluene in urine and expired air was 51.9% and that of m-xylene was 26.9%, for 10 hours after the administration. Furthermore, the excretion rate of both 10 hours' expired air and 48 hours' urine, was 66.7% for toluene and 56.6% for m-xylene. 4. The ratio of 48 hours' urinary excretion to 10 hours' expiratory excretion was 0.77 for toluene and 3.58 for m-xylene. These results indicate that toluene was excreted more in expired air than in urine whereas m-xylene was mainly excreted in urine.

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In order to estimate the influence of phenobarbital on the metabolism of m-, p-xylene, female Wistar rats were pretreated with intraperitoneal injection of sodium phenobarbital (75 mg per kg body weight) for 3 days (PB group). On the 4th day, 4.667 mmole per kg of m-xylene or p-xylene was injected intraperitoneally and urine samples were collected at 4 hour intervals thereafter. The urinary content of m-methylhippuric acid and p-methylhippuric acid· was determined by high-performance liquid chromatography. Urinary excretion of m-methylhippuric acid or p-methylhippuric acid in the PB group was significantly higher than in the control group (pretreated with 2 ml per kg of normal saline instead of phenobarbital) at the 0-4 hour and 4-8 hour intervals (p<0.01). This suggests that oxidation of methyl groups of m- and p-xylenes can be performed by the microsomal drug metabolizing enzyme in liver. There was no significant difference between the PB and control groups in the amount of m-methylhippuric acid and p-methylhippuric acid excreted during the first 48 hours after administration.

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