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<P>1. It is possible to isolate the immune bodies from the globulin fraction, which was obtained by the salting out with ammonium sulphate or electrodialysis, by the biologic method. The rate of isolation is almost the same as the rate of the isolation by the biologic method. 2. The isolated serum from the globulin fractions by the combination of the physical or the chemical with the biologic method, has less antigenic and nitrogen contents than the isolated serum by the biologic method alone; especialy the isolated immune substance by the combination of the physical with the biologic method has the least antigenic contents. 3. The best results are obtained in the physiologic salt solution at 65℃, for the isolation of precipitin by means of the combination of the physical with the biologic method.It is a pleasure to express my indebtedness to Prof. Ogata for the encouragement and valuable suggestions which he has given. I am also indebted to Dr. Sunouti for various assistance he has offered in the preparation of this work.</P>

Fur vorliegende Mitteilung stellte ich Untersuchungen an uber Isolierung der Antifibrinogenprazipitine sowie uber die Spezifitat des Fibrinogens mittels des isolierten Prazipitins. In den zur Ausfuhrung gelangten und hier behandelten Versuchen ist mir die Isolierung des Antiplasma- und Antifibrinogenprazipitins gelungen. Das isolierte <P>Antiplasmaprazipitin enthalt immer zwei Prazipitinarten, Antiserum- und Antifibrinogenprazipitin, und wahrend sich zwischen beiden Prazipitinen im Plasmaantiserum ein grosser Unterschied an Menge erkennen lasst, so besteht kein Unterschied zwischen diesen beiden isolierten Prazipitinen, weil das Fibrinogen fur das Antigen bei der Prazipitinisolierung geeignet ist und mehr Antifibrinogenprazipitin als Antiserumprazipitin frei gemacht wird. Die beiden Quotienten, Biudungs- und Isolierungsquotient, des Antifibrinogenprazipitins sind immer grosser als die des Antiserumprazipitins. In anderen Worten ausgedruckt bildet das Antifibrinogenprazipitin bei der Mischung mit Antigenen eine festere Biudung als das Antiserumprazipitin, und auch bei der Isolierung wird eine grossere Prazipitinmenge frei gemacht. Vergleicht man miteinander die Titer des isolierten Antifibrinogenpraizipitins mit den Fibrinogenen verschiedener Tierarten, so findet man Folgendes: a) Antirinderfibrinogenprazipitin gegen Fibrinogen von Riud 1OO%, Ziege 25%, Hund 1.5%, b) Antiziegenfibrinogenprazipitin gegen Fibrinogen von Ziege 1OO%, Rind 25%, Hund 1.5%. Aus obigen Ergebnissen konnen wir erkennen, dass die Artspezifitat der Rinder-, Ziegen- und Hundefibrinogene bei der Untersuchung mittels isolierter Antifibrinogenprazipitine deutlicher zu unterscheiden ist als die beim genuinen Immunserum (Rinderfibrinogenantisera: mit Rinclerfibrinogen 100%, mit Ziegenfibrinogen 50% und mit Hundefibrinogen 7%; Ziegenfibrinogenantiserum: mit Ziegenfibrinogen 100%, mit Rinderfibrinogen 37% und mit Hundefibrinogen 6%.). Die Prazipitine, die nach Bindung mit einen anderen Fibrinogen (z. B. Ziegenfibrinogen) aus Sera der mit einem Fibrinogen (z. B. Rinderfibriuogen) vorbehandelten Kaninchen isoliert worden sind, reagieren in gleicher Weise sowohl mit homologem (Rinderfibrinogen) als auch mit heterologem Fibrinogen (Ziegenfibrinogen). D. h., aus der Reaktion des isolierten unspezifischen Prazipitins konnen wir ersehen, dass sich dabei die Spezifitat gegenuber dem heterologen Antigen deutlich erhoht. Deswegen konnen wir auch beweisen, dass die Reaktion auf Rinderfibrinogen deutlich spezifisch und die auf Ziegenfibrinogen nicht spezifisch ist; daher stellt sich auch durch die Untersuchung mittels des isolierten Antifibrinogenprazipitins die Artspezifitat als hoher heraus wie mittels genuinen Serums.</P>

<P>1. The cardiac muscle fibres of the rabbit swell more and more in the course of the artificial uremia. In the early stage of the disease, this swelling is almost confined to the sarcoplasm, but later the fibrils take part in it also. In the latter stage of the disease, the swelling of both of these two becomes considerable, so that the muscle assumes a characterized feature. 2. The cardiac muscle fibres of the rabbit made artificially oedematous show a swelling also, but in this case the sarcoplasm takes only a little part in it. 3. The cardiac muscle of the rabbit submitted to the urea-injection bears a close resemblance to the finding seen in the case of the artificial uremia. 4. The histological changes of the cardiac muscle caused by the uremia are chiefly due to the urea or its analytic substance retained in the blood, the oedematous stagnation of water having little concern in it. In closing this paper, I wish to express my best thanks to Dr. K. Kosaki under whose guidance this work has been performed.</P>

Generally, of all the visceras, the ovary is the commonest place for cyst-formation, and the majority of all the ovarial cysts are multilocular pseudomucinous forms. Lieppert states that it occupied 53.6% and by Stubler and Branders, 30.6% and by Pfannestiel, ca. 2/3 of all the ovarial cyst. ･ In many cases, it is one sided (ca. 90%) and moreover is pedunculated, and as the epitherial proliferarion of the tumor is almost unlimitedly repeated and so it is, indeed, possible to become a wonderful size. We have never seen any other tumor which can grow so large like the ovarial pseudomucinous tumor. Therefore, when I consider the reason that, even now, we sometimes meet with a gigantic ovarial cyst like these, considering from the side of patient, I can cite the following facts ; first : the extreme terror of surgical operation, second : they have been left behind in the march of progress of civilization, and third : the poverty of their family, etc. In my cases, all the patients are either country people living far off from the civilized city, or those disliked the operation, and on the other side, the wrong diagnosis of the doctor and the midwife, which took it for pregnancy. These facts should be also considered in connection with it. Probably it may not be an error to attribute one of these reasons in Case 1. Such a monstrous tumor looks as if it occupies the whole abdorninal cavity and it extremely presses the abdominal visceras and diaphragma. The Kaufmanns case mentioned previously shows that the height of its diaphragma is in the Ist intercostal space in the left side and the 4th rib at the right. Consequently the thoracic visceras are also pressed and causes some trouble in the heart and lungs. These disorders are, however, gradually recovered after removal of the cyst, as all of my cases have proved. The carrier of the head and extremities are rather the appendages of the tumor. Still the patient becomes very thin and her face characteristically shows the so-called "" Facies ovarica "" which is quite different from cachexy, but a similarity of feature is observed in those who are suffering from the said disease and it appears as if they are related each other. The development of the cyst is generally very slow but its monstrous one is rapidly enlarged at certain period. It appears at any age, old or young, mostly between 20 and 50, and especially Mainzer, Olshausen and the author have reported cases of very aged woman. The size of cyst varies from the very small to the marvellous monster one and it is not infrequently reported as mentioned before that the weight of cyst exceeds the body-weight. The gigantic cyst, of course, interrupts pregnancy, delivery and puerperium. The monstrous cyst consists of the so-called a large main chamber and many small accessory chambers and some are very tense in consistence. It, is mostly spherical in shape and all of my cases are like irregular gourd which is generally seen in literature. The surface of cyst is generally white-pearty, glittering appearance, but following the alteration of the content, of each chamber, its surface changes to yellow, black and yellowish-brown or dark red-color. The contents of the cysts are changeable ; sometimes are very diluted serous or mucinous but generally thick mucous and frequently become very viscid. The monstrous cyst posseses various substances secondarily. As to the constitution of the contents, Scherer and Eichwald ever said that it consists of paralbumin and metalbumin but as a matter of fact there exists no albumin. Hammarsten named it pseudomucin, illustrating from his view point ; Pfannenstiel noted that it is not so simple substance and Mizukoff proved the existence of paramucin. Histologically the lumen of cyst is lined by a single layer of irregularly arranged cylindric epithelium having nuclei and glittering protoplasmas that lie at the bases of the cells and they quite resemble to the germinal epithelium of the intestine. Lahm reported that there are rarely seen the dark black colored spots on the inner surface of the cyst lumen and these are consisted of the cells which contained lipoidofuchsin-group-pigments. No particularity was noticed in my cases. There are also found various secondary changes in ca. 60% of all the cases. The torsion is said to occur in from 10 to 20% of cases, and sometimes it fil]ally goes to the resection of the peduncle. The rupture of cyst-wall is not so infrequent and it results the seed-metastasis of the benign tumor of same kind. Metastasis after removal of the cyst is very rare but Olshausen and Baumgarten reported the benign metastasis in the parietal cicatrix and Schrader and Polano, the malignant metastasis. The perforation of cyst to the adjacent viscera is very infrequent Hemorrhage, infection, suppuration and calcareous infiltration are sometimes observed. Again, the complication of pregnancy also cannot be excepted and this is also seen as that of dermoidcyst but its occurrence is ca. 2%. Pfannenstiel marked that pseudomucinous cyst is frequently combined with the dermoidcyst. It is, however, infrequent (4- 5%) from the stand point of my experience and I can not agree with the view that the cyst-formation of dermoidcyst is proliferated from the pseudomucinous cyst. The most frequent occurrence in the secondary changes is the adhesion to the adjacent visceras. But it is not serious and even if it is in an advanced stage can be removed easily. Of all the changes, the malignant degeneration is the most troublesome (according to Stubler and Branders it is 6.7%) and its etiology is still unknown. It is said that in long existence of the cyst in advanced aged woman, the malignant degeneration appears but in my case 3 in aged woman, though I devoted myself to its observation up to her death. I could not find any symptom of malignant degeneration, and the author had experienced in an aged woman of 86 years old whose ovarial cyst gradually grew in two or three years after it was found, and it attained to the size an adults head but he was unable to find the symptoms of malignant degeneration either. On the contrary, I even had an experience of miserable case of a woman of 23 years old in pseudomucinous ovarial cyst, who in only a year's progress after the cyst was found, it clearly happened to be carcinomatous degeneration and came to a sad end of exploratory laparotomy. How does this malignant degeneration occur ? As to its causes , I have contributed nothing but explain with many vague words which now require further investigation. I think that it can not be put in one class at all and I attribute this to an individuality of the cyst-carrier. It may be convenient to settle the question, if I explain it, as a cause of carcinoma also. Such a malignant degeneration, in this case, is very infrequent and it would certainly be an object of research in future. Finally, the auther expresses his respectful thanks to Dr. Ando, Professor of the Okayama Medical University for his revisal.

1. Im leichten Stadium der Clonorchiasis sinensis bei Kaninchen zeigt der Harn kaum irgendeine Veranderung ; man darf also aus dem Harnbefunde schliessen, dass im leichten Stadium keine Stoffwechselstorung eintritt. 2. Beim schweren Stadium kommen folgende Stoffwechselanomalien zum Vorschein : a) Das Korpergewicht und die Harnmenge nehmen ab, der Harn wird sauer, sein spezifisches Gewicht steigert sich und der Gallenfarbstoff tritt in ihm zu Tage. b) Das Harnammoniak, das wesentlich zur Neutralisation der im Organismus gebildeten Sauren dient, vermehrt, sich stark. c) Der Purinstoffwechsel, d. h. die Urikolyse, wird stark gehemmt. d) Der Zerfall des Korpereiweisses wird gefordert. e) Die Harnstoffbildung und der Kreatininstoffwechsel, die bekanntlich in der Leber vor sich gehen, werden kaum gestort. 3. Es konnte gleichzeitig konstatiert werden, dass die Sektions- und histologischen Leberbefunde des schwer erkrankten Organismus mit den schon von mehreren Autoren erzielten grut ubereinstimmen.

Wenn die Prazipitation bei Bindung zwischen Toxin und Antitoxin spezifisch im engeren Sinne, wie Ramon, Hoen, Zippe und Tschertkow u. a. behaupten, hervorgerufen wird, so ergeben sich aus obigen Versuchsreihen viele Tatsachen, die dem widersprechen. Erstens ist dieses Prazipitinphanomen nicht lediglich eine Reaktion zwischen Toxin und Antitoxin, wie es Ramon u. a. mit Prozonenphanomen verteidigen, weil mit Serumprazipitin oder BakterienPrazipitin dieselbe Reaktion gezeitigt werden kann, wenn man die Immunisierungsweise und Verdtinnungsweise der Antigene und des Immunserums moglichst unter denselben Bedingungen vornimmt, Um die namlichen Phanomene mit gewohnlichem Prazlpitin deutlich nachzuprufen, muss man mit stark hochimmunisiert,em Prazipitinserum in grossem Umfange die Reaktion in so weit verdiinntem Antigen und Antikorper beobachten, dass man bei beiden die Hemmung am schwach verdunnten Teile erkennen kann. Zweitens mochte ich die Reinheit der Toxinlosungen serologisch diskutieren. Von der Antigenitat fur Prazipitinbilclung aus gesehen, enthalt die Toxinlosung eine geriuge Menge von Bakterieneiweiss, die durch Antibakterienimmunserum mittels Prazipitinreaktion nachweisbar ist, wenn auch bei Ineinem Versuche der Bouillonstoff ganz ausgeschlossen werden kann. Umgekehrt, wenn man mit verschiedenen Antitoxinseren mittels Prazipitinreaktion oder Komplementbindung zwischen Toxin oder Bakterienextrakt arbeitet, so reagieren diese Antitoxine mit beiden Antigenen immer positiv. Auf Grund dieser Tatsache darf man annehmen, dass das Bakterieneiweiss an der Prazipitinreaktion zwischen Toxin und Antitoxin stets mitbeteiligt ist. Drittens will ich Prazlpitinwert und Antitoxinwert kurz vergleichen. Wenn man ideal reine Toxine als Antigene benutzt oder solche, die sehr wenig Bakterieneiweiss enthalten, so konnte der Parallelismus zwischen Antitoxinwert und Prazipitinwert irgend einen naheren Zusammenhang haben. Doch um diese quantitativen Beziehungen festzustellen, muss man Prazipitinbildung durch Bakterien und Toxin selbst scharf differenzieren oder mit einwandfreiem Toxin, das mit Antibakterienprazipitin nachweislich keine Reaktion zeigt, die Prazipitinreakt,ion nachweisen. Bei meinem Versuche zeigen beide Werte in einigen Fallen Parallelismus, aber in vielen Fallen eine grosse Abweichung. Viertens mochte ich uber Resistenz der Toxinlosung gegen physikalische oder chemische Einwirkung auf Toxitat und auf Prazipitinogenitat einiges hinzufugen. Gegen aussere Einwirkung ist, wie schon bekannt, die Toxitat sehr labil, die Prazipitinogenitat dagegen sehr stabil. In dieser letzteren Hinsicht ist die Prazlpitinogenitat der Toxinlosung noch resistenter als Serumantigene und steht den Bakterienantigenen naher. Und diese Beziehungen sind denen aus passiver Anaphylaxie gleich, weil das durch Antitoxinserum (Prazipitintiter 1 : 50) sensibilisierte Tier auf Reinjektion von Toxin oder Bazillenextrakt nach 24 stundiger Inkubation auch mit denselben Symptomen der Anaphylaxie reagiert wie beim Prazipitinversuche. Aus Antitetanusseren kann ich auch etwas verminderte Sympbome bei Toxinreinjektion nachweisen.

After the experimental removal of the most part of caecum of rabbit, when it is bred over 100 days, the remained portion of the caecum is enlarged distinctly and not only the spiral plicae increases its number but it is partly formed a peculiar caecal-dilatation, projecting against the colon-side. The muscular layer of caecum-wall is generally thickened, especially the epithelium is markedly proliferated. This is a regenerative phenomenon on the caecum of which damaged portion is to be filled and partly regains the characteristic shape of caecum and at the same time shows the systematical changes on the whole caecum-tissue. Consequently it may be admitted that these changes are not merely the regeneration of tissue of caecum but it is a regenerative process as an organ. However, literature on this subject hold the same view that each tissue of intestinal canals of mammalia is independently regenerated but the regeneration of an organ is not acknowledged. Korschelt states in his book that " Die ausgebildeten Wirbeltiere zeigen keine eigentliche Regeneration der einzelnen Abschnitte des Darmkanals. Wenn von einer solchen die Rede ist, handelt es sich nur um den Ersatz von Teilen der Schleimhaut, die sowohl im Magen, wie in den darauffolgenden Darmpartien stattfindet . . . ". On the other hand, the fact shown by my experimental results on mammalia such as rabbit, proved the regenerative process of intestinal canals, and I believe that it is a new information which overthrows the old established view. On the subject of caecumregeneration, Schmalhausen and others have alreacly pointed out that the morphotgenesis of the regenerated organ or tissue is closely connected with the function or its mechanical element, and in case of the regenerative process of rabbit-caecum, its functional relation is undoubtedly the important factor. There are many theories on the caecum-function and caecum of herbivorous animal such as rabbit plays an important role on the digestion and resorption of cellulose as it has been hitherto marked by Tullberg Ustjnzezw Elllenberger and others. Any herbivorcus animal which takes food which is rich with cellulose, posseses the large caecum, and it is a well known fact that Such food taken is stored in the caecum for a long while and sufficient liquid and putrefactive action decompose the cellulose and completely digests. The remained portion of the excised caecum of rabbit partly regains its peculiar cul-de-sac which is physiologically formed as above described, and at least it may be said that the anatomical structure of caecum in which the intestinal contents isolated from the main intestinal canals is stored for a long while which signifies an importance of its function and again a part of the morphological changes in caecum-regeneration is probably a functional adaptation concerning the digestion and resorption of cellulose. Among the intestinal-tissues, the mucous membrane manifests most distinctly its regenerative activity and also the epithelium of mucous membrane on the originally remained portion of caecum is remarkably proliferated. Thus the defect of the caecum-tisseue is compensated by the hypertrophy. Such proliferation is not observed in all the intestinal canals except the caecum alone. Therefore, the epithelium of the caecum appears to monopolize this special function which the small intestines and colon are unable to compensate.

A urinary iron excretion test was carried out in 22 patients with iron deficiency anemia. The iron excretion index was significantly higher in patients with intractable iron deficiency anemia compared with normal subjects and anemic patients who were responsive to iron therapy. The findings suggest that iron excretion may be a factor that modulates the response of patients to iron therapy.

Cytogenetic studies were performed on a biopsy specimen of a jaw tumor and on a bone marrow aspirate from a Japanese patient with Epstein-Barr virus-negative Burkitt's lymphoma. A 14q + chromosome was found in cells from either source, although each contained a different clone. Other karyotypic abnormalities present in common included 2dir dup (1q) (q21 leads to q32), 3q+, 6p--, +12, +mar.

Function of pituitary-thyroid axis was studied in rats with experimentally induced thyroiditisWistar strain female rats were immunized with homologous thyroid extract in Freund's complete adjuvant and with simultaneous intradermal injection of pertussis vaccine concentrate. They received booster shots at the first and third week after the initial immunization. Serum thyroid hormones and TSH were measured just before, and at weekly intervals after, the initial immunization. Histological examination of the thyroid gland at the second week after immunization showed slight infiltration of macrophages in the thyroid follicles. From the third to the fourth week, massive lymphoid cell infiltration and destruction of follicular architecture developed in all immunized rats. Serum R3 levels slightly decreased during the second week, increased transiently during the third week, then decreased again thereafter. Serum T4 levels decreased slightly durinf the fourth week. Serum TSH levels were not elevated significantly during the third week, but the response to TRH was significantly increased at this time. Basal TSH levels were increased during the fourth week. The TRH test was a sensitive method capable of detecting minimal failure of thyroid function undetected by other routine measuremens of thyroid hormones and TSH.

A recently modified method using peroxidase labeled antibodies for light and electron microscopic demonstration of hepatitis B virus (HBV) was applied to the evaluation of hepatitis B surface antigen (HBsAg) on the surface of liver cells in biopsy specimens from 24HBsAg chronic carriers. Membranous distribution of HBsAg was demonstrated in diffuse or scattered hepatocytes in all 4 asymptomatic carriers and in 3 of the 20 patients with HBsAg-positive chronic active hepatitis or liver cirrhosis. In these patients with membranous expression of HBsAg, hepatitis B e antigen, Dane particles and DNA polymerase were often detected in sera, and large amounts of hepatitis B core antigen appeared in the liver. These results suggest that membrane-bound HBsAg may be expressed by the HBV genome. The ultrastructural study of liver cells showing membranous expression disclosed dense deposits of reaction product indicative of HBsAg on the cell membrane and/or on assembled particles within the extracellular space. In some hepatocytes showing both diffuse cytoplasmic and membranous expression of HBsAg, HBsAg-positive membrane of cisternae open to the intercellular space was connected with the liver cell membrane. These findings supported the conjecture that HBV associated antigens are integrated into the liver cell membrane.

In electron microscopic observation of a liver biopsy obtained from a hepatitis B surface antigen-positive patient, noncoated core particles were occasionally seen budding into the hepatocytic cisterni and many Dane particles were found in the pericanalicular vesicles of hepatocytes. Noncoated core particles were also localized in clusters within the bleb of microvilli. There were some core particles being protruded from microvilli into the lumen of bile canaliculi by budding. These findings suggest hepatitis B virus being released from the hepatocyte to the bile canaliculi by two different modes; through vesicle by reversed phagocytosis and from the microvilli by budding.

Basilar arteries with experimental vasospasm were studies histochemically using a catecholamine fluorescence technique in 15 cats. Fluorescence microscopy of normal vessels revealed abundant catecholamine fluorescence in the adventitia and in close contact with the media, but none within the media. Experimental subarachnoid hemorrhage resulted in depletion of catecholamine fluorescence in the adventitia and in its appearance in the media. In vessels with vasospasm which lasted for 2 or 5 h and responded to vasodilators, fluorescence was scarce in the adventitia, but abundant in the media. In vessels with vasospasm unresponsive to spasmolytic agents, fluorescence was observed neither in the adventitia nor in the media. The results suggest that noradrenaline in the media of spastic arteries plays an important role in the development of cerebral vasospams.

A near diploid clone derived from a rat liver cell line was continuously treated with various concentrations of 3'-methyl-4-dimethylaminoazobenzene (3'-Me-DAB) in culture. By treatment with 2.8 micrograms/ml, cells with 41 chromosomes formed a mode and which then shifted to 39. The chromosome numbers of cells treated with 5.4 micrograms/ml were widely distributed at early stages, but later the mode shifted to hypotetraploid region. Untreated control cells were confirmed as near diploid. Increased plating efficiency by 3'-Me-DAB as well as the appearance of large sized colonies was obtained. The production of alpha-fetoprotein (AFP) by the cells was slightly enhanced by treatment with 3'-Me-DAB. The cells treated with and without 3'-Me-DAB did not produce any tumor in rats 6 months after their intraperitoneal injection.

Immune complexes in liver specimens from 10 patients with chronic liver diseases [2 with chronic persistent hepatitis (CPH), 3 with chronic aggressive hepatitis (CAH) of moderate activity, 3 with CAH of severe activity, and 2 with liver cirrhosis] were examined by a technique of direct immunofluorescence using FITC-labelled human purified Clq (FITC-Clq). FITC-Clq bound to the nuclei of all cells in liver tissue. After DNase treatment, positive nuclei were absent, but positive staining with FITC-Clq remained in amorphous deposits and hepatic cell membranes in the areas of piecemeal necrosis of four CAH patients. Since FITC-Clq could not be demonstrated in the liver tissue of CPH and liver cirrhosis which contained no piecemeal necrosis, positive fluorescence in the liver of CAH patients was thought to indicate immune complexes bound to FITC-Clq. The fact that these positive substances, however, were few in number, may be the result of physiological mechanisms of immune clearance which rapidly eliminate immune complexes from the body.

A papillary (villous) adenoma of the duodenum was found in a 67-year-old male. Radiographic barium studies of the upper gastrointestinal tract revealed a tumor in the second portion of the duodenum. Biopsied specimens taken through a duodenofiberscope showed papillary adenoma. A partial duodenectomy with duodenojejunostomy was performed. The specimen was a pedunculated tumor measuring 3 X 2 X 1.5 cm. Histologically, the tumor was composed of villous and tubular arrangements of mucus-secreting columnar epithelial cells. A moderate number of entero-endocrine cells and a few Paneth cells were also noted. Forty-two other cases reported in Japan are briefly reviewed.