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1. Die Zuckerausscheidungsschwelle bei experimentellem Stauungsikterus von Kaninchen wird im allgemeinen herabgegesetzt. 2. Der Glykogengehalt der Leber bei experimentellem Stauungsikterus bzw. in seinem Anfangsstadium wird ubernormal vermehrt gefunden. Dagegen wird er bei langandauerndem experimentellen Stauungsikterus herabgesetzt. 3. Bei Langandauerndem Stauungsikterus besitzt die Leber noch die Fahigkeit zur Glykogenbildung. 4. Aus den Daten scheint mir hervorzugehn, dass die Herabsetzung der Zuckerausscheidungsschwelle bei experimentellem Stauungsikterus von Kaninchen auf der vermehrten Zuckerassimilation im KaninchenQrganismus beruht. Diese vermehrte Zuckerassimilation scheint mir durch die uberschussige Zufuhr der Gallensaure ins Blut bei Stauungsikterus bedingt zu sein. Zum Schlusse ist es mir eine angenehme Pflicht, Herrn Prof. Dr. T. Shimizu fur seine freundliche Leitung und Anregung im Verlaufe dieser Versuche meinen herzlichsten Dank auszusprechen.

1) Im Kaninchenorganismus werden die intravenos verabreichten verschiedenen Zucker in der Reihenfolge Frucht zucker, Traubenzueker. Mannose und Galaktose ansteigend im Harne ausgeschieden. 2) Bei experimentellem Stauungsikterus wird die Zuckerausscheidung im Harne am 2. Tage nach der Operation in der Reihenfolge Traubenzucker, Fruchtzucker, Mlannose und Galaktose absteigend herabgesetzt, wahrend sie am 5. Tage naeh der Operation in der Reihenfolge Fruktose, Glukose, Mannose und Galaktose absteigend herabgesetzt wird. Diese Herabsetzung der Zuckerausscheidung tritt am 5. Tage nach der Operation viel deutlicher hervor als am 2. Tage. 3) Der Glykogengehalt der Leber, sowohl bei normalen Kaninchen als auch bei denen mit experimentellem Stauungsikterus, wird in der Reihenfolge Lavulose, Glukose, Mannose und Galaktose absteigend gebildet. Die Glykogenbilduntg der Leber aus verschiedenen Zuckern bei experimentellem Stauungsikterus wird am 2. Tage nach der Operation uber normal gesteigert, wahrend sie am 5. Tage nach der Operation unter normal herabgesetzt wird. 4) Die Glykogenbildung der Leber aus verschiedenen Zuckern geht am 5. Tage nach der Operation bei experintentellem Stauungsikterus nicht parallel mit der herabgesetzten Zuckerausscheidung im Harne. Diese Erscheinung ist nach meiner Meinung durch die infolge des Hungerns verursachte Steigerung der Zuckerverbrennung im Organismus bedingt, die eine unter normal herabgesetzte Glykogenbildung am 5. Tage nach der Operation zur Folge hat. Die uber normal gesteigerte Glykogenbildung am 2. Tage nach der Opeation scheint mir auf der durch Rtickfluss der Galle, vermehrten Gallensaure im Blute zu beruhen. zum Schlusse ist es mir eine angenehme Pflicht, Herrn Prot. Dr. T. Shimizu fur seine freundliche Leitung und Anregung i:n verhbufe dieser Versuche meinen herzlichsten Dank auszusprechen.

Ich untersuchte in diesem Kapitel die Spezifitat des Fibrirnogens mittels Komplementbindungsreaktion, wobei fur jedes Immunserum, wie bei Prazipitation, eine fur die Bindungszone geeignete Antigenmenge gebraucht wurde. Die Ergebnisse meiner obigen Versuche dtirften sich folgendermassen zusammenfassen lassen : Es lasst sich mit Sicherheit nachweisen, dass das mit dem Fibrinogen einer Tierart gewonnene Antiserum die Fahigkeit besitzt, Komplemente zu binden, wenn es nicht nur mit dem ihm entsprechenden Antigen, sondern auch mit dem Fibrinogen anderer Tierarten zusammengebracht wird. Wie zu erwarten, erweist sich jedoch das Immun-serum dem entsprechenden Fibrinogen gegenuber als viel starker wie gegenuber einem Fibrinogen anderer Tierarten. Der Titer nach der Konrplementbindungsmethode ist indes stets viel niedriger als der nach der Prazipitinrnethode. Wenn man aber die Titer der hoch immunisierten Antisera gegen Fibrinogen verschiedener Tierarten bei Komple-mentbindung miteinander verg]eicht, so bemerkt man, dass sie mit den Resultaten bei Prazipitation fast parallel gehen, d. h. das Fibrinogen weist auch mittels der Komplernentbindungsreaktion gleichzeitig beicle Spezifitaten, Art- und Organspezifitat, auf, z. B. Z.F.A. S. 3 und H. F.A. S. 3. Von den bei niedrigem Prazipitintiter gezeigten Immunsera verbinden dagegen die einen das Komplement mit Fibrinogen oder

1. Die Zuckerausscheidung im Harne des stauungsikterischen Kaninchens wird bei Zufuhr von Traubenzucker im allgemeinen unter Normal herabgesetzt, wahrend sie bei Zufuhr von Lavulose nicht nur nicht unter Normal herabgesetzt, sondern vielrnehr uber Normal vermehrt wird. Aus diesem Befunde geht hervor, dass die Lavulose bei Stauungsikterus keine Nierenschwelle besitzt. 2. Die Glykogenbildung der Leber aus Glukose wird bei experimentellem langdauerndem Stauungsikterus im allgemeinen unter Normal herabgesetzt. Der Glykogengehalt der Leber ist 4 Stunden nach der Zufuhr des Zuckers hoher als 3 Stunden nach ihr. Aus den Daten erhellt, dass die Glykoi genbildurlg bei langdauerndem Stauungsikterus uber den normalen Ztistand hinaus verlangsamt wird. 3. Die Glykogenbildung der Leber aus Glukose bei langodauerndem Stauungsikterus, die unter Normal abgeschwacht ist, wird durch die Zufuhr der Gallensaure wieder uber Normal gesteigert. Diese ubernormal gesteigerte Crlykogenbildung der Kaninchenleber mit langdauerndem Stauungsikterus tritt bei Zufuhr von Gallensaure 4 Stunden naeh der Zufuhr des Traubenzuckers starker auf als 3 Stunden nach ihr. 4. Die Glykogenbildung der Leber mit langdauerndem Stauungsikterus ist 3 Stunden nach der Zuckerzufuhr bei Lovulose hoher als bei Glukose, wahrend 4 Stunden nach der Zuckerzufuhr jene bei Lavulose geringer ist als bei Glukose. Diese Daten zeigen, dass Lavulose auch bei Stauungsikterus fur die Glykogenbildung der Leber viel schneller als Glukose verwertet wird. 5. Die Glykogenbildung der Leber mit langdauerndem Stauuntgsikterus aus Lavulose wird sowohl 3 als auch 4 Stunden nach der Zuckerzufuhr durch die Zufuhr der Gallensaure uber Normal gesteigert. Diese durch die Gallensaure bedingte gesteigerte Glykogenbildung tritt ,sowohl bei Zufuhr von Glukose als auch bei der von Lavulose auf. Auch bei Stauungsikterus wird Lavulose sowohl bei Zufuhr als auch ohne Zufuhr der Gallensaure viel schneller und 3 Stunden nach der Zuckerzufuhr besser, 4 Stunden nach ihr schlechter als Glukose fur die Glykogenbildung der Leber verwertet. Aus den oben erwahnten Daten scheint mir hervorzugehen, dass die bei langdauerndem Stauungsikterus unter Normal herabgesetzte Glykogenbildung aus Glukose und Lavulose auf der ungenilgenden Gallensaurebildung in der Leber beruht, obwohl die durch Ruckfluss der Galle verursachte gestorte Leberfunktion berucksichtigt werden muss. Vorliegende Daten gestatten wohl die Schlussfolgerung, dass die ubernormal gesteigerte Glykogenbildnng im Anfangsstadium des Stauungsikterus durch die uberschtissige Zufuhr der Gallensaure ins Blut bedingt ist. Zum Sohlusse ist es mir eine angenehme Pflicht. Herrm Prof. Dr. T. shimizu fur seine freundltohe Leitung und Anregung im Verlaufe dieser Versuche meinen herzlichsten Dank auszusprechen.

The effectiveness of tranexamic acid treatment for sudden deafness was studied in detail. The results of treatment with tranexamic acid administration in 19 cases (25 ears) of sudden deafness and two historical control groups using various treatments were compared by the chi square contingency test. The data suggested that tranexamic acid treatment may be superior to traditional treatments especially if treatment is begun early. Among ears treated with tranexamic acid, 11 ears (44%) were healed or recovered remarkably, 8 ears (32%) recovered slightly and 6 ears (24%) were unchanged or worsened. Fibrinolysis in the inner ear may be the pathophysiology of sudden deafness. Treatment with tranexamic acid starting within 4 days after onset of symptoms was most effective in patients whose initial audiogram was flat or concave, initial average hearing loss at 5 frequencies (250 Hz, 500 Hz, 1000 Hz, 2000 Hz and 4000 Hz) was between 23 dB and 76 dB (mean; 45.1 dB) and was not accompanied by dizziness.

For the detection and characterization of circulating immune complexes (CIC) in various liver diseases, a Clq binding test was used. Though the CIC level was almost normal in HB surface antigen (HBsAg) positive asymptomatic carriers, the level increased in patients with liver diseases. During acute exacerbation of chronic viral hepatitis, the CIC level reached peaks 1 to 3 weeks before and after the hepatic cell necrosis. Study of the sedimentation rates of CIC in various liver diseases showed CIC in the 19s-22s region and in the 7s-19s region. In acid buffer, CIC was dissociated into 5 to 6 components by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). In one case of HBsAg positive severe chronic aggressive hepatitis, CIC was composed of HBsAg, IgG and another three or four undetermined components. During acute exacerbation of chronic hepatitis, minor changes of these dissociation patterns of CIC were observed.

To elucidate the latent state and reactivation of Epstein-Barr virus (EBV) in non-neoplastic lymphoid lesions, we investigated 144 non-neoplastic lymphoid lesions by in situ hybridization (ISH) to detect the expression of EBV-encoded small RNAs (EBER)-1 and BCRF-1 and by immunostaining for latent membrane protein (LMP)-1 and ZEBRA. ISH for EBER-1 detected EBER-1-positive cells (EPC) in 31 of the 144 examined lesions (22%). EPC were detected in 4 of 49 cases of nonspecific lymphoid hyperplasia, in 16 of 20 abscess-forming granulomatous lymphadenitis (AFGL), 5 of 25 Kikuchi's disease, and in 3 of 3 infectious mononucleosis. LMP-1 was expressed in 6 of 124 non-neoplastic lymphoid lesions (4.8%). LMP-1-positive cells were observed in 6 of the 31 EBER-1-positive cases (19%). EPC were detected significantly more frequently in LMP-1- and ZEBRA-positive specimens than in the LMP-1- and ZEBRA-negative specimens. BCRF-1 was expressed in 4 of 11 cases examined: 2 of 3 AFGL, 1 of 2 Kikuchi's disease, and in the 1 case of atypical lymphoid hyperplasia. This study suggests that Epstein-Barr virus is prevalent and can be reactivated in the lymph nodes effaced by destructive inflammation, such as AFGL. Such inflammation may provide a local milieu that is conducive for EBV to enter the lytic cycle.

The establishment of a model system of neoplastic transformation of normal human cells has been attempted with a chemical carcinogen, 4-nitroquinoline 1-oxide (4NQO). In the course of these experiments, it was noticed that immortalization of human cells is a multi-step process involving several mutational genetic events. Thus, chromosomal changes which occurred during the process of immortalization of human fibroblasts were examined. To accomplish immortalization, fibroblasts obtained from an embryo were repeatedly treated with 10_-6M4NQO from primary culture to passage 51 (59 treatments in total). Before immortalization, some chromosomes (especially, chromosomes 2, 6, 8, 10, 11, 12, 15, 19, and 20), were lost at a relatively high frequency. After immortalization, the chromosomes distributed so broadly in the triploid to hypotetraploid region without a distinct modal number or without marker chromosomes that it was difficult to identify the specific chromosomes related to the immortalization of human cells. No specific structural chromosomal changes were detected. Although the significance of such chromosome changes in relation to immortalization is not clear, the loss of some specific chromosomes suggests that genes which are involved in cellular aging and which suppress immortalization may have been lost in the immortalization process.

Tissue PIVKA-II was examined in 32 hepatocellular carcinomas and 2 metastatic liver tumors using indirect immunofluorescence, and the results were compared with the size, histological grading and serum PIVKA-II level. The specificity of this method was confirmed by the disappearance of reactivity in PLC/PRF/5 cells after the addition of vitamin K to the culture medium. Positive PIVKA-II staining was observed as a clustered or a single cell pattern only in the HCC nodules, but not in the surrounding cirrhotic tissue. PIVKA-II staining was observed in all HCC groups regardless of histological grade. There was no relationship between PIVKA-II staining and the size of HCC. PIVKA-II was detected immunohistochemically even in small HCC of patients whose plasma PIVKA-II levels were below the detection limit. These results suggest that PIVKA-II production is a specific phenotype of HCC regardless of its histological grading and demonstrate that this immunofluorescent PIVKA-II staining is more sensitive and useful than plasma PIVKA-II assay for the diagnosis of HCC.

Rat Kupffer cells were observed and counted under a scanning electron microscope after a single dose of zymosan. The cell number increased after 24 h and reached 2 times the control after 72 h. The percentage of cells presenting numerous microvilli increased from 24% to 86% over the same period. Carbon clearance, a measure of phagocytic activity, decreased temporarily, regained control values after 12 h, and attained a 4-fold elevation at 72 h. Phagocytic activity paralleled Kupffer cell number, but increased more relatively. This result probably reflected activation of resident Kupffer cells as noted by numerous thick microvilli.

Six quantitative psychometric tests were performed on 51 healthy subjects, 19 cirrhotic patients with subclinical hepatic encephalopathy (SHE), 32 cirrhotic patients without SHE, and 26 patients with other diseases. Strong correlations between age and the results of all the psychometric tests were observed in the healthy subjects (p less than 0.005). Sex and etiology of liver cirrhosis did not affect the test results. SHE patients, compared with non-SHE and health subjects, presented impairment in the ability to perform the tests, even in the absence of obvious clinical and electroencephalogram findings. In SHE patients, trailmaking test A (TMT A) yielded the highest frequency of abnormal values, 63%. TMT A results were abnormal in 80% of SHE patients with abnormal scores in other tests, and thus it seemed to be the most sensitive test. Liver function tests did not correlate with psychometric testing in any of the groups. Blood ammonia levels in SHE patients with abnormal TMT A scores correlated with TMT A scores (r = 0.752, p less than 0.01); this was not the case in SHE nor non-SHE patients with normal TMT A results. These data demonstrate the usefulness of psychometric tests in detecting SHE.

The basilar artery was exposed transclivally , and a vascular spasm was produced by topical application of a lysed erythrocyte solution. The maximum fall in the mean arterial blood pressure (MABP) after administering of 2 micrograms/ kgBW and 15 micrograms/ kgBW of PGI2, ranged from 35 to 45 mmHg and from 65 to 85 mmHg, respectively. The drop in MABP after an injection of papaverine hydrochloride (1.5 mg/ kgBW ) was between 30 and 40 mmHg. If MABP did not fall, the vessel diameter did not change. Although papaverine elicited marked dilation of both normal and spastic basilar arteries, PGI2 did not dilate normal basilar arteries and produced only a slight dilation of spastic basilar arteries. Subarachnoid hemorrhage (SAH) was simulated by an intracisternal injection of fresh autologous arterial blood 3 days prior to experimentation. Changes in regional cerebral blood flow (rCBF) were measured by the heat clearance method, before and after an intravenous administration of either PGI2 or papaverine hydrochloride. Changes in rCBF fell into 3 categories: Type A, no change; Type B, a change which varied with the arterial blood pressure, and Type C, an increase rCBF despite systemic hypotension. Type A or B was observed in 17 out of 19 cats with SAH in which PGI2 was administered intravenously, and Type C was observed in only 2 cats. Thirteen untreated control cats produced a Type A or B response in 12, and Type C response in only one cat. There were no significant differences between the control and SAH groups. When 15-hydroperoxy-5, 8, 11, 13-eicosatetraenoic acid (15-HPETE) was infused, the same results prevailed. Papaverine hydrochloride increased rCBF either transiently or continuously in all cats. These results suggest that PGI2 dilates extracranial rather than intracranial vessels regardless of the presence or absence of cerebral vasospasm.

A 26-year-old male with renal allograft, who received immunosuppressive treatment with azathioprine, presented marked elevations of serum biliary tract enzymes, such as gamma-glutamyl transpeptidase (5,609 units/l) and alkaline phosphatase (60.5 Bessey-Lowry units), 14 months after transplantation. Two months later the patient became icteric; he died of respiratory failure 19 months after the renal allograft. Postmortem examination revealed intrahepatic cholestasis with minimal inflammatory cell infiltration, indicating drug hepatotoxicity.

Descriptions are carried on the method how to separate the indirect bilirubin from the chloroform extracts of the dried dog's gallbeadder bile by adsorption chromatography. 1. The optimal concentrations of the bilirubin content were 2 to 4 mg/100 ml when 1 ml of the sample was adsorbed on the Tswett tube of about 10 mm diameter. 2. Though several zones of the indirect bilirubin were separated on the column of silica gel when developed with various solvents, these zones were proved to be mingled with some oxidized or other intermediate products and the separation like this was thought to owe to the activity of the adsorbents. 3. The chromatogram of the crystalline bilirubin resembled to the one formed by the indirect bilirubin in the chloroform extracts. 4. The chromatogram of the chromatographically separated indirect bilirubin was similar to the former. 5. The absorption maxima of a chloroform solution of the natural indirect bilirubin existed at 450 mμ in the visible range, and it was the same as the maxima of the crystalline bilirubins.

1. Sinomenine and Irgapyrin, the two antirheumatics known to be capable of releasing histamine, caused a marked gastric secretion in the unanesthetized dog. 2. The facial edema and itching associated with histamine release by sinomenine was almost completely eliminated by NeoAntergan, but the gastric secretion was not suppressed, or rather increased - an observation also reported by Paton and Schachter with Compound 48/80. This indicates that the histamine release cannot be markedly prevented by antihistamine agents in this animal. 3. The gastric secretion induced by Irgapyrin was not suppressed by Neo-Antergan but Irgapyrin originally never caused other symptoms associated with histamine release. This is probably due to the antihistamine action inherent in this compound itself. 4. No such histamine-releasing activity, as determined by gastric secretion, could be observed in aminopyrine or butazolidine sodium, the components of Irgapyrin. 5. Sinomenine, differing from Irgapyrin and Compound 48/80, was ineffective by intramuscular injection.

In decerebrated cats the impulse discharges were detected by means of an unipolar microelectrode from a single inspiratory neuron in the respiratory centers, and the change in discharge produced by administration of stimulating, as well as depressant agents, was studied. The results were summarized as follows. 1) Inhalation of the air containing all. excess of carbon dioxide, as well as the air deficient of oxygen and the intravenous administration of a small dose of caffeine, aminocordine and lobeline produced a) a remarkable increase of frequency of impulses in the stage of constant frequency of the volley, b) a rapid increase of frequency of impulses in the stage of crescent frequency of the volley and c) a shortening of the duration of the volleys, as well as of silent periods. 2) In narcosis by a moderate dose of morphine, as well as in the recovery stage from apnea produced by over-ventilation, there were observed the phenomena which were exactly opposite to those described in 1). 3) It was concluded that a most essential sign by which one can discern whether the activity of the respiratory Genters is raised or depressed, is the changes of the frequency of impulses produced from an inspiratory neuron. The expense of this research was defrayed from the grant in aid of the Ministry of Education.

1) As the boundary of the outgrowth zone of the bone marrow culture is sharply defined from the surrounding area and the cellular density becomes very high in leukemia, diagnosis can be made with ease and certainty. 2) The differential diagnosis between aleukemic leukemia and aplastic anemia becomes easy by application of the tissue cuIture method. 3) The vital observation of blood cells were used in classification of leukemia by cellular systems, and it was discovered that there were a lot of patients with monocytic leukemia and relatively many with acute lymphatic leukemia. 4) Because the cellular growth in the bone marrow culture of aplastic anemia declines extremely and abundant fat cells are observed, the diagnosis of this disease is easily made by employment of this method.

(1) The movement of the blood cells in the bone marrow was classified into 9 types. (2) The characteristics of moving types are so distinct according to the kinds of blood cells, that the differential diagnosis of the cells by moving types is easily and certainly made. In this way, (by the kind of blood cells), we have classified leukemia, as is described in our other articles. (3) The phagocytosis and vital staining of the blood cells in the bone marrow is different in degree and mode, according to the kind of blood cells, and thus becomes valuable ground for the differential diagnosis of the cells.