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With the purpose to elucidate morphologically the site where fat synthesis takes place in the cell, electron-microscopic observation has been conducted on the interscapular brown fat tissue of mice at various periods of carbohydrate introduction after starvation. By starving mice, the depot lipids in the brown fat have been discharged almost completely, and the carbohydrate introduction has caused the biosynthesis of lipids from carbohydrtates in the same tissue. Observations on the tissues proved that the lipogenesis in the brown fat tissue cells takes place in the ground substance keeping the intimate correlation with the endoplasmic reticulum but not in the mitochondria.

Homogenous grafting of the ovary to patients of ovarian dysfunction all proved to be effective, but the degree of the effectiveness and the time of appearance of effect of the grafting were not fixed. Moreover, there was no relationship between the effectiveness of grafting and the type of blood. If the various conditions at the time of grafting are taken into· consideration as above mentioned, this operation utilizing as it does the ovary usually discarded at operation may be expected to bring about quite a satisfactory therapeutic result.

The grafting itself can be successful only when the type of blood between the recipient and the donor of the ovary meets the requirements for blood transfusion. In the case of success in the grafting, a marked activity of the grafted ovary can be observed about two months afterward by the vaginal smear method, but no cyclic phenomenon can be recognized nor biphasic picture suggestive of the progesterone activity in the basal body temperature.

From the histochemical studies of cytocyrome oxidase on the striated muscles of the cats and mice, the following results have been obtained. The three types of muscle fibers are distinguishable by the activity of cytochrome oxidase from each other as by the succinic dehydrogenase activity, namely, the red muscle fibers show a high cytochrome oxidase activity, the medium fibers a moderate activity, and the white muscle fibers a low activity. And it is suggested that these three types of fibers are different in their respiration, metabolism and have the different functions.

From these findings, we confirmed that the tongue-like process formations of the cells which are still believed as the platelets formation by many investigators, would be nothing but the presentation of the cell degeneration and platelets are separated only from the tips of tentacles.

From the histochemical studies of succinic dehydrogenase on the striated muscle of the fish, frog, bird and mammal, the following results were obtained. (1) The red muscle fiber shows a higher succinic dehydrogenase activity, while the white muscle fiber a lower activity. The third type of muscle fiber "medium fiber", which is intermediate in the succinic dehydrogenase activity between the red and white muscle fiber, is observed practically in all of the striated muscle of mammals. (2) There is a good parallelism between succinic dehydrogenase activity and stainability to Sudan black B among the three types of muscle fibers. (3) From the nature of the constituent fibers, muscles can be divided into three groups, i. e., gastrocnemius type, soleus type and diaphragma type. (4) Those belonging to the gastrocnemius type are composed of three types of fibers, i. e., those of large size, low in activity of succinic dehydrogenase reaction and low in sudanophilicity; those of small size, high in enzymatic activity and in sudanophilicity; and those of medium size, moderate in enzymaticactivity and in sudanophilicity. (5) Those belonging to the soleus type, are composed of fibers almost equal in size which can be divided into two by the enzymatic activity and sudanophilicity, excepting the few with low enzymatic activity. (6) Those belonging to diaphragma type, are composed of three kinds of fibers showing different enzymatic activity as in the case of gastrocnemius type, but there is no correlation between the size and the enzymatic activity and sudanophilicity differing from the latter. (7) The difference in succinic dehydrogenase reaction as demonstrated among three types of fibers is due to the difference in number or in activity of mitochondria. (8) The pigeon breast muscle is composed mostly of red muscle fibers, and a few white muscle fibers, while the sparrow breast muscle is composed only of red muscle fibers. (9) The bloody colored muscle of the fish corresponds to the red muscle of the mammals. The white muscle of the fish is composed of three types of fibers. (10) The frog muscle is cmposed of three types of fibers.

With a view to study the blood vessel construction in cervical cancer the author prepared the reconstruction models and the results to be described below were obtained by three-dimensional observations carried on the models. 1. The arteries in the surrounding tissues of cancer are markedly proliferated, and in the surrounding tissues they present the formation of blood-vessel bands. 2. The spiral formation or corkscrew-like formation presented by blood vessels in the bands in the surrounding tissues of cancer seems to be the characteristic of arteries. 3. As for the direction of flow of arteries in the tissues surrounding cancer, the arteries in the normal case generally run slanting towards the surface of the cervix in the direction of the periphery, but the arteries in the surrounding tissues of cancer run towards the cancer tissue. 4. Apart from mother blood vessels, the blood vessels in the cancer tissue all present an imperfect capillary·like construction and there is none that possesses the normal arterial or venous con struction. Some part is dilatated and other part is narrow, suggesting an imcomplete blood supply. The direction of the flow is also irregular. Mother blood vessels grow rapidly large once they are taken into the cancer tissue. 5. All blood vessels other than the mother vessels reveal an imperfect capillary-like coustruction in the cancer tissue, and in places the walls of these blood. vessels are indistinct; and consequently it is but natural that they bleed so easily.

In order to determine the steps with which the reaction of neotetrazolium chloride reduction conjugates in the terminal electron transport system, an analytical study on the neotetrazolium reduction by tissue homogenates was carried out using various substrates such as sodium succinate, p-phenylenediamine, sodium malate, sodium α-glutamate and DPN, and inhibitors such as sodium malonate, potassium cyanide and antimycin A, as the results the following conclusions were drawn. 1. The reaction of neotetrazolium reduction by tissue homogenate using sodium succinate as substrate is mainly the succinoxidase system reaction; and the reaction takes place conjugating about 50 per cent in the step of the succinic dehydrogenase system (succinic dehydrogease, cytochrome b and cytochrome C1), of these about 15 per cent conjugates in the step prior to the antimycin A sensitive step and 35 per cent in the step itself; and about 50 per cent in the step of cytochrome c oxidase. 2. In the case using p-phenylenediamine as substrate the reaction of neotetrazolium reduction is the reaction due to the activity of cytochrome c-cytochrome oxidase system; and when p-phenylenediamine is used with the sufficient amount of cytochrome c, the reaction appears to be dependent on cytochrome c oxidase activity. Neotetrazolium reduction in all these reactions takes place conjugating in the step of cytochrome c oxidase. 3. In the case where DPN and substrates taking DPN as a coenzyme are used, the reaction of neotetrazolium reduction is mainly the reaction conjugating at the step below antimycin A sensitive step in the DPNHcytochrome c reductase system (flavoprotein, cytochrome b and cytochrome c;), probably with the flavoprotein of DPNH-dehydrogenase. 4. Endogenous dehydrogenase reactions are the sum total reactions conjugating at the steps prior to the antimycin A sensitive step in the terminal electron transport system and with other various reduction systems which are not inhibited by antimycin A.

From the histochemical study of DPN and TPN diaphorase on the striated muscles of the cats, the following results were obtained. 1. M. gastrocnemius, which belongs to the white muscle by naked eye, consists of three types of muscle fibers distinguished by the DPN diaphorase staining: namely, the small muscle fibers, i. e., the red muscle fibers show a moderate activity, being stained pink, while the large muscle fibers, i. e., the white muscle fibers show a low activity, being stained faint pink. The. third type of muscle fibers: namely, the medium fibers are stained pale pink and show the enzymatic activity intermediate between the red and white muscle fibers. 2. M. soleus, belonging to the red muscle by naked eye, consists of three types of fibers distinguished by the DPN-diaphorase staining, i. e., the red muscle fibers are stained pink, medium fibers pale pink, and a few white muscle fibers faint pink. The diameters of these three types of muscle fibers in M. soleus are almost the same. 3. From the staining pattern of TPN-diaphorase in M. gastrocnemius and M. soleus, the three types of muscle fibers can be distinguished by TPN-diaphorase activity, namely, the red muscle fibers show a high TPN-diaphorase activity, being stained purple, while, the white muscle fibers a low activity, being stained pale pink. The medium fibers are stained pink and show a moderate enzymatic activity intermediate between the red and white muscle fibers. 4. The TPN-diaphorase activity is higher than the DPN-diaphorase activity in the striated muscle, but it is less active than the TPN-diapborase activity in the kidney. However, the activity of DPN-diaphorase in the striated muscle is quite lower than that of the kidney.

With an improved method of tissue culture of peripheral leucocytes of our own design, the authors carried out systematic observations on the peripheral leucocyte culture from the normal, various kinds of leukemias, leukemoid reactions, and hypoplastic anemia. As for the culture method we have devised a method of silicon oil coating on the blood containers, a method which will least affect the cell function as compared with the conventional culture method. As the results we have found that the tissue growth in the case of peripheral leucocyte culture of normal persons ceases after six-hour culture and also we have recognized a peculiar finding, a growth like a corona-shape, in which an empty space appears in the inner part of growth area along with the lapse of time. In every leukemic case, without presenting growth area like a corona, the cell density is high and the outer zone of growth area becomes sharply demarcated as in the case with bone-marrow culture and also the growth continues even after 12 hours. At this instance we have noticed many mitoses of immature cells. Moreover, the maturation of immature cells has been observed and it has also been possible to distinguish to what type these immature cells belonged. In the leukemoid reaction no growth pattern Characteristic to the leukemia can be recognized, and at a glance it can easily be differentiated from the leukemia. In the case of hypoplastic anemia although the growth area is like that of the normal presenting a corona-like shape, the cell density is lower and the function of leucccytes is lesser than the normal. From these results we believe that the peripheral leucocyte culture is clinically useful.

With the purpose to study sideroblasts as a means of diagnosing blood diseases and to pursue the metabolism of non-hemin iron in erythroblasts we investigated sideroblasts (erythroblasts containing iron granules stainable by Prussian blue) under various erythropoietic conditions in the human and rabbits, and obtained the following results: 1. In blood diseases the proportion of sideroblasts in the case of low erythropoietic condition is higher and in the case with accelerated erythropoietic condition and of iron deficiency it tends to be lower than that in normal persons. Further, obtaining sideroblastogram and sideroblast ratio (S. r.) from the classification of Types I, Ⅱ, and Ⅲ according to the iron granule content, it has been proven that abnormal conditions can be clearly distinguished from the normal, indicating that sideroblasts are closely associated with erythropoietic function. This is proven to be a far superior method for the diagnosis as well as for the prognosis of blood diseases than the determination of serum iron. 2. In experimental anemic rabbits the relationship of sideroblasts to the condition of erythropoietic function is still more clearly recognized, and it has been found that variations in the sideroblast count is dependent upon the condition of the equilibrium between the iron supply from serum iron and the iron utilization controlled by the erythropoietic function. 3. In addition, in the iron-treated rabbits under various erythropoietic conditions we have been able to confirm that there are a certain mechanism and a limitation to the iron intake by erythroblasts, and that erythroblasts take essentially three steps of metabolic processes, namely, intake, retention, and utilization of iron almost simultaneously, in the latter half of the maturation stage.

According to the method presented in the first report the author mixed ferric iron solution and serum with the various proportions of serum and iron, limiting the pH level of the media wihin 5.4 to 8.3. It was found there was a certain level exceeding which the iron could no longer move with protein on the paperelectrochromatography. The maximum level was found to be81, 500γ% in the case of ferric chloride and 77, 200γ% in ferric ammonium sulfate, when the bovine serum was used as a protecting colloid. The iron added in excess of this level was found retarding at the starting line suggesting the formation of gross iron hydroxide colloid.

1. α-Aminoadipic acid and lysine are increased in the urine of thyroidectomized dog. 2. Pipecolic acid is increased in the urine of rat treated with thyroid extract. 3. Relation between thyroid function and lysine metabolism is discussed.

By mixing ferric iron with serum protein, 20 cc of serum and 1 cc of ferric chloride or ferric ammonium sulfate (l0 mg ferric iron/cc in each), in the range of pH 5.4 to 8.2, a transparent brownish red colored solution can be obtained. Paperelectrochromatography proved the iron can mainly be detected in β-globulin fraction in bovine serum and in &#945-globulin and albumin fractions in human and rabbit sera. But the absorption spectrum proved that there is no formation of any new compound, giving almost the same absorption curve as in the serum protein itself. And by lowering the pH of media below 5.4, the solution gives immediately the positive reaction of ferric iron. From these rerults it is suggested that iron will be maintained in a colloidal state keeping the stability of this state in the presence of protein molecules. Freezing and drying are the procedures quite useful for keeping this material for a long period of time without changing the chemical characteristics.

1. Considering an imaginable important role of histamine in inflammations or allergic reactions, some clinical and experimental studies were made for the purpose of findings the relationship of the pathological changes of A. P. to local histamine. 2. Gingivae in the case of A. P. showed a remarkable quantitative increase of histamine, compared with those in the case of normal healthy controls. It could be noticed that this increase had an increasing tendency in proportion to the degree of inflammatory pathologic changes in the gingiva. 3. In the gingivae of A. P. an increase of mast cells and their morphologic changes, particularly disintegration, were seen and the grade of changes was almost parallel to an increase of histamine. 4. When a histamine solution was repeatedly injected into the mucobuccal folds of animals, a remarkable increase of histamine and mast cells in the injected gingivae were recognized with inflammatory changes. An increase of gingival histamine could be hardly recognized by means of a simple mechanical stimulation or local anaphylaxis alone. However, in the combination of two, the increase of histamine was seen and relatively remarkable inflammatory changes suggestive of A. P. were macroscopically and microscopically noticed. 5. Topical applications of the ointment mixed with sinomenine, histamine-liberating substance, and benadryl, antihistamine substance, repeated every other day in the gingival pockets, showed favorable effects in slight or early cases of A. P. 6. These observations suggest the existence of both possible role of histamine in the development of local pathologic condition of A. P. and allergic processes in etiologic factors of the disease.

The iron introduced into vein in the form of the serum iron colloid is rapidly incorporated into ferritin and hemoglobin in a markedly high level with the increase in their amounts, without showing any ill effects. Experiments also show that there is another course of iron metabolism for the incorporation into ferritin and hemoglobin than the physiologic course by the aid of metal combining protein. This is true, however, only in the case in which the normal function of RES is retained. The incorporation of iron into ferritin and hemoglobin is accelerated in anemic animals and delayed in those having RES whose function is disturbed. From these results the author would suggest that the anemic patients may be given a quantity of iron in the form of serum iron colloid directly into vein without causing any side effects.

Electron microscopic observations revealed that the serum ferric chloride mixture prepared in the range of pH 5.4 and 8.2 is of colloidal solution whose particles are composed of electron-dense iron colloid nuclei surrounded by protein cortex formed by the absorption around the iron colloid particles. The elevation of pH over 9.0 or the lowering below pH 3 in media results in the loss of the protein cortex enhancing the growth of each molecule to longer ones and to coagulate with each other. Ferritrat proved to have almost the same cortex surrounding the iron colloid as that of serum ferric chloride mixture, but the colloid particles were larger than those of the latter. Both Ferrobalt and the gelatin ferric chloride mixture are of colloid solution but the colloid particles are heterogenous both in size and shape and have no cortex part. Glufericon will be true solution of organic iron complex.

The fibrous components of the metacarpophalangeal (MP) joint including the palmar plate, the collateral ligament and the dorsal plate were studied with particular attention paid to the fibrous structure of the fibrous tendon sheath and the deep transverse metacarpal ligament. The tough fibrillar structure around the MP joint, especially the force nucleus, consisted of three types of mixed fibers: the fibrous tendon sheath of the A1 pulley, the deep transverse metacarpal ligament, and the palmar plate. The tendon sheath was located on the ulnar side in the index and middle fingers, on the central position in the ring finger, and on the radial side in the little finger. These fibrous connections among the fingers formed a transverse arch in the hand. The palmar plate of the MP joint was relatively rigid and appears to function as a cushion when flexed. A fold-like protrusion of the synovial layer of the palmar plate of the MP joint had a meniscoid function, which was larger than that of the proximal interphalangeal joint. The capsule of the MP joint was thicker at the dorsal area, forming a dorsal plate, which is a sliding floor of the extensor mechanism and has a meniscoid function for joint congruity. The main lateral stabilizer consisted of collateral ligaments and accessory collateral ligaments anchored to the palmar plate. These structures act together as a "phalangeal cuff", connecting the proximal phalanx to the metacarpal head and sta

Helicobacter pylori (H. pylori) infection in the stomach is etiologically closely associated with chronic active gastritis, peptic ulcer, gastric cancer and gastric mucosa-associated lymphoid tissue lymphoma. In this study, we examined the antibody responses and cytokine profiles of three strains of mice (BALB/c, C3H/He, and C57BL/6) infected with H. pylori. Following this, correlations between host-immune reactions and intensity of inflammation were analyzed. H. pylori (ATCC43504) was intragastrically administered once a week to the mice from 4 weeks of age, and they were sacrificed at the ages of 4 and 7 months. In these mice, we examined the histology of the stomach, antibody titers against H. pylori, and serum levels of cytokines (IL-4, IL-10, TNF-alpha, IL-2 and Interferon-gamma). In BALB/c mice, inflammation of the stomach was minimal. Inflammation was observed in 63.6% of C57BL/6 mice and 33.3% of C3h/He mice. In C57BL/6 and C3H/He mice, all the cytokines tended to increase. In contrast, BALB/c mice were inactive in cytokine production except for IL-2. Two C3H/He mice developed severe inflammation with lymph follicles; one showed a response largely typical of Th-1, and the other showed a response largely typical of Th-2. Although a definite correlation was not shown between Th-1/Th-2 response evaluated by cytokine production and intensity of inflammation, it appears that in H. pylori-induced inflammation both cell-mediated (Th-1) and humoral (Th-2) immunity play a role in pathogenesis.

The main purpose of this study was to evaluate the inhibitory effects of 5-fluorouracil antineoplastics, cephem antibiotics containing the methyltetrazolylthiol (MTT) group and antidiabetics on aldehyde dehydrogenase (ALDH) activity in vivo and in vitro. In in vivo experiments, rats were given a 100 mg/kg dose of drugs (10 mg/kg for glibenclamide) orally or intraperitoneally. When each drug was administered singly immediately after an oral administration of 1.5 g/kg ethanol, only carmofur, an antineoplastic, produced marked increases in blood acetaldehyde concentrations. This action was also noted when ethanol was ingested 15 h after administration. The remaining drugs did not increase blood acetaldehyde concentrations. When rats were treated with carmofur at 12 h intervals for 3 consecutive days and were given 1.5 g/kg ethanol after the final treatment, blood acetaldehyde concentrations were elevated more significantly than with a single administration of carmofur. Furthermore, daily administration of cephem antibiotics containing the MTT group, latamoxef, cefamandole, cefoperazone and cefbuperazone, significantly increased blood acetaldehyde concentrations. Daily administration of sulfonylurea antidiabetics, chlorpropamide and acetohexamide, slightly increased blood acetaldehyde concentrations. Drugs causing increases in blood acetaldehyde concentrations when administration was combined with ethanol ingestion also inhibited ALDH activity in vitro. The results of the in vitro experiments roughly correlated with those of the in vivo experiments. The inhibitory effects of drugs on ALDH activity were in the following order: carmofur >> cephem antibiotics containing the MTT group > sulfonylurea antidiabetics.