Tetsuro Anzai

AFP‐PRODUCING CELLS IN HEPATITIS AND IN LIVER CIRRHOSIS

Examination of biopsy specimens from 16 patients with acute hepatitis and 30 with liver cirrhosis and of autopsy specimens of cirrhotic livers from 12 patients with primary hepatoma to detect cells containing alpha fetoprotein (AFP) was carried out by immunofluorescence. AFP was observed in the cytoplasm of proliferating cells having the appearance of oval cells and transitional cells in hepatitis and cirrhosis cases suggesting that differentiation from oval cells to mature hepatocytes is one of the regeneration mechanisms of hepatocytes in these diseases and that the transient appearance of AFP reflects the regeneration process. Supporting evidence is that AFP-containing cells were proliferating in the regenerating area of the liver in a subacute hepatic necrosis case who had a very high serum AFP level. There is a similar relation between AFP production and fetal gestation.

Morphological changes in the liver of rats treated with a new hypolipidemic agent, S-8527

Abstract Electron microscopy was used to investigate the effect of a new hypolipidemic agent, 1,1-bis[4′-(1″-carboxy-1″-methylpropoxy)-phenyllcyclohexane (S-8527), on the fine structure of hepatocytes of rats, treated with oral doses of S-8527 for 2, 3 or 14 weeks, and the effect was compared with that of clofibrate. Daily doses of 150 or 300 mg/kg of S-8527 caused a qualitatively similar pattern of changes in cell organelles to that caused by clofibrate, such as increased number and size of microbodies, proliferation of tubules and vesicles of smooth endoplasmic reticulum (SER) and deformation of mitochondria. At the same dose level, S-8527 appeared to cause an equal grade of changes to those caused by clofibrate, whereas there was no marked change at dose levels of 10 mg/kg and 30 mg/kg of S-8527. S-8527 was also found to cause less increase in relative liver and a more marked hypolipidemic result than clofibrate.

Incidences of Three Different Fetal Proteins in Sera of Patients with Primary Hepatoma

Incidences of 3 different fetal proteins alpha fetoglobulin (F) alpha 2 hepatoprotein (H) and beta S in sera of patients with primary hepatoma are reported. Primary hepatoma tissues obtained at autopsy were used for extraction of antigens. 4 fetal livers intrauterine ages 5 6 7 and 9 months were obtained by toxicological surgeries. The incidence of alpha F was the highest of the 3 fetal proteins and the occurrence of this protein in adult sera was strictly specific to primary hepatoma. Although the incidence of beta S in sera of patients with primary hepatoma was the lowest of the 3 fetal proteins this fetal protein was also detectable in 12.2% of sera from patients with malignancies other than primary hepatoma. Both alpha 2H and beta S were detectable in a small number of sera from patients with nonneoplastic diseases of the liver. Immunofluorescence studies were employed to demonstrate the cytoplasmic localization of alpha F and beta S in the fetal liver.

Immunochemical study of vaginal secretion. I. Detection of serum and non-serum protein components in normal vaginal secretion.

Summary Vaginal secretion from 55 healthy adult volunteers were analyzed with the double diffusion-precipitin test using antisera to serum proteins and antisera to bronchial secretions, as a preliminary study in search of an immunological means of detecting cancer of the cervix. Approximately one-half of the specimens contained detectable amounts of serum proteins, while 70% reacted with the anti-sputum sera. Of these, 18 specimens (32.7%) reacted with the anti-sputum serum absorbed with normal human serum proteins. Characterization of the components reacting with the antisera was achieved with the immunoelectrophoretic study, and the immunoelectrophoretic patterns of vaginal secretions were compared with the patterns of gastric juices and of bronchial secretions. The 3 secretions had components having cross-reactivities although their physico-chemical properties were different. Use of antisera to vaginal secretions and application thereof to pathologic vaginal secretions are indicated.

Immunochemical studies of gastric juice from patients with carcinoma of the stomach

In an a t tempt to introduce immunochemical methods of gas t r ic juice analysis into the s tudy of diagnosis of s tomach carcinoma, ant igen extract ion f rom gas t r ic juice obtained by intragas t r ic neutral izat ion, as well as prepara t ion of an t i sera thereof , was carr ied out. The highmolecular we igh t mater ia ls of gas t r ic juice were subjected to gel fi l tration using Sephadex G-200. Normal gastr ic juice could be divided into four f rac t ions consis t ing of two carbohydrater ich f rac t ions (I and II), one protein-rich, carbohydrate-poor f rac t ion (IV) and a f rac t ion appearing between II and IV (III). The inhomogenei ty of the four f rac t ions was evidenced by t he absence of paral le l ism between each of the carbohydrate cons t i tuents (hexose, hexosamine, fucose and sialic acid) and protein. Each of tke chromatograms of samples f rom pat ients wi th ulcer, a t rophic gast r i t i s and s tomach carcinoma was character ized with unique changes of the gel f i l t rat ion pat terns . Each of the f rac t ions was subjected to cellulose acetate electrophoresis, acrylamide-agarose double gel electrophoresis , double diffusion precipi t in tes t and to immunoelectrophoresis . Although leakage of serum proteins was especially remarkable in samples f rom pat ients wi th atrophic gas t r i t i s and s tomach carcinoma, the pathologic samples were a lso character ized wi th quanti tat ive as well as quali tat ive changes of protein mater ia ls unique to gas t r ic juice. This method, however, did not disclose presence of any carcinoma-specific ant igenic mater ia l . Studies are being directed to a combinat ion of other chromatographic as well as electrophoret ic methods of fract ionat ion.

Studies of gastric mucosal urease and serum urease-inhibiting protein

The specific existence of gastr ic urease, as well as the physiological significance of ammonia in gastr ic juice, has been the subject of controversy. The present study was undertaken in order to elucidate this problem. Results indicated that there was a parallelism between the gastr ic juice ammonia content and the parietal cell response to gastric secretion. A close correlation was found between ammonia contents of visible mucus and of soluble mucin. These results , together with the observation of pH-activity curves (Nikoloff) of mucosal urease preparat ions obtained f rom freshly resected stomachs, supported the view that ammonia in gastr ic juice resulted from gastr ic mucosa, and that s tomach mucosal urease had an active physiologic significance in the protection of stomach mucosa from hydrochloric acid secretion through the production of ammonia. The precipitation reaction between human serum and jack bean urease (Freisinger) was also studied, and increases in the precipitin t i tres in sera of patients with gastric ulcer were demonstrated. Studies on the nature of the reaction revealed that this was chiefly due to a2macroglobulin which was apparently different from anti-urease antibody. It was also demons t rated that the activity of s tomach mucosal urease was inhibited by a2-macroglobulin. The suggested mechanism of the increase of urease-inhibitory a2-macroglobulin in sera of pat ients with gastr ic ulcer was discussed.

Semi-Quantitative Immunoelectrophoresis and Its Application to the Study of Serum α-Globulins.∗

Summary A method is described for making direct and simultaneous quantitation of the subfractions of serum proteins by a modification of the immunoelectrophoretic method. By applying the method to the study of serum α-globulin subfractions, highly significant correlations were observed between biochemically determined values and intensities of their immunoelectrophoretic reactions. The method is simple, yet satisfactorily reproducible, and has a promising applicability to the study of pathologic physiology of the subfractions of serum proteins.