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This experiment was carried out to evaluate the possibility of degradation of d-lactate into formate and acetaldehyde. In order to induce hyperproduction of d-lactate in rats. Donryu male albino rats were fed diets containing 0.064% 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB), 4'-methyl-4-dimethylaminoazobenzene (4'-MDAB) or 2-methyl-4-dimethylaminoazobenzene (2-MDAB) for 10 weeks. During the experiment, body mass, food and water intake and volume of urine were documented. Methylglyoxal, d-lactate and formate in the urine samples were determined. On the first day of the eleventh week, methylglyoxal, d-lactate, glutathione and enzymatic activities of demethylation and glyoxalase I and II in liver were measured. Methylglyoxal, d-lactate and clinical chemistry parameters of blood plasma were also measured. The levels of methylglyoxal and d-lactate in livers of rats fed 3'-MDAB were very high, while those of 2-MDAB fed-rats and the control group were the same. The fact that glyoxalase I activity and the level of glutathione, a cofactor of glyoxalase I, were high in the livers of the 3'-MDAB-fed rats can explain the elevated levels of methylglyoxal and d-lactate in the liver. The most striking results were the elevated formate levels in the urine of rats fed 3'- and 4'-MDAB in a precancerous state. The degradation of d-lactate, an end product of the methylglyoxal bypass, into acetaldehyde and formate was suggested as a possible way to explain the results.

The insulin-like growth factor I receptor (IGF-IR) is exceptionally overexpressed in many cervicalcancer-derived cell lines. It is postulated that a decrease of p53 protein levels due to human papillomavirus (HPV) infection may contribute to the up-regulation of IGF-IR expression in cervical cancer cells because transcription of IGF-IR is strictly down-regulated by p53. To evaluate this fact in clinical cervical cancer specimens, we checked the expression levels and activated status of IGF-IR by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens obtained by conization or hysterectomy were stained with anti-IGF-IR and with an antibody recognizing phosphorylated tyrosine at its c-terminus. The expression levels of IGF-IR were significantly high in cervical intraepithelial neoplasia (CIN) III and invasive cancer specimens. Phosphorylation of IGF-IR was promoted in all CIN and invasive cancer specimens, and its intensity was related to the promotion of lesions. Interestingly, IGF-IR overexpression was missing in the basal layer of CIN I and II lesions, whereas it was evenly distributed in CIN III and invasive cancer lesions. This IGF-IR overexpression pattern may be utilized in the diagnosis of HPV infection status in CIN lesions.

In order to make the mechanism concerned with the sound-susceptibility in the organ of Corti clear, we observed the organ of Corti with the phase-contrast microscope, after the microdissection of the cochleae in human, dogs, guinea pigs and hamsters by Engstroöm's surface preparation technique. As a result, we have formulated a hypothesis for the mechanism of the sound-susceptibility in the organ of Corti. Further, we have inferred the contrary recruitment phenomenon (hypothesis), by explaining theoretically such a clinical fact as the recruitment phenomenon or the cochlear hearing loss by applying our first formula of hypothesis. Finally, we described the application of the contrary recruitment phenomenon (hypothesis) to the early discovery or diagnosis of the false normal ear or cochlea, in other words, latent hearing loss.

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.

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.

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 comparison was made of the clinical findings of 59 patients with liver cirrhosis (LC) accompanied with hepatocellular carcinoma (HCC) (of which 35 had ascites and 24 did not at the time of admission) and 164 patients with LC, but without HCC (of which 39 had ascites and 125 did not). HCC patients were older and more often had hepatomegaly, vascular spider and pleural effusion than LC patients. Ascites was more frequently observed in HCC than in LC patients when the serum albumin level and the indocyanine green disappearance rate were relatively well maintained and when peripheral edema was absent. There was no difference in the ascitic protein concentration between LC and HCC patients. Malignant cells were detected in ascites only in 14% of the HCC patients. These facts indicate the presence of ascites-inducing factors in HCC patients which have no direct relation to serum colloid osmotic pressure and effective hepatic blood flow. Almost all of the HCC patients with ascites (96%) died with ascites, whereas 54% of the LC patients with ascites recovered from the ascitic condition.