K. Ariga

THE α‐FETOPROTEIN‐PRODUCING CELLS IN THE EARLY STAGE OF THE EXPERIMENTAL LIVER CANCER

In the early stage of the experimental liver cancer caused by the azo-dye feeding of rats, an appearance of serum a-fetoprotein (AFP) was recognized by Hirai and his co-workers (the first response). So-called “oval cells” (OnoC et al.) were detectable only in this stage. There is speculation that the appearance of AFP in the first peak of DAB-induced hepatic carcinomas is produced by the so-called oval cells, and in the second peak by tumor cells. Therefore, in order to identify the AFP-producing cells, this study was made by the direct immunofluorescent antibody method.

Cellular sites of glutamic oxaloacetic transaminase in pig liver by fluorescent antibody method

GOT isoenzymes of pig liver have been analysed by immunodiffusion and immunoelectrophoresis in agar gel, and further their hepatic cellular sites of them have been investigated by indirect fluorescent antibody method; supernatant GOT and mitochondrial GOT are quite different enzyme protein immunologically, and the former consists of four subcomponents migrating to the anode, while the later includes two subcomponents moving to the cathode and one to the anode, while specific fluorescence of s-GOT is seen in very small granules within hepatic cells, of which some positively stained cells are occuring singly or in groups throughout the lobules. m-GOT positive cells are rather diffusely distributed throughtout the lobules, and its distribution pattern is different from that of s-GOT. Cells other than hepatocytes, Kupffer cells and endothelial cells in the sinusouds are not stained for s-GOT or m-GOT.

Cellular sites of glutamic oxaloacetic transaminase in pig liver by fluorescent antibody method: Running head: Cellular sites of got in pig liver

SummaryGOT isoenzymes of pig liver have been analysed by immunodiffusion and immunoelectrophoresis in agar gel, and further their hepatic cellular sites of them have been investigated by indirect fluorescent antibody method; supernatant GOT and mitochondrial GOT are quite different enzyme protein immunologically, and the former consists of four subcomponents migrating to the anode, while the later includes two subcomponents moving to the cathode and one to the anode, while specific fluorescence of s-GOT is seen in very small granules within hepatic cells, of which some positively stained cells are occuring singly or in groups throughout the lobules. m-GOT positive cells are rather diffusely distributed throughtout the lobules, and its distribution pattern is different from that of s-GOT. Cells other than hepatocytes, Kupffer cells and endothelial cells in the sinusouds are not stained for s-GOT or m-GOT.

Clinical and pathological study of acute severe hepatitis

An attempt was made to differentiate subacute hepatitis, which shows histological change of submassive hepatic necrosis and serious clinical signs, i.e., hemorrhagic tendency, ascites, edema and or mental disturbance, from acute hepatitis at the early stage before the development of these signs. Present history and various hepatic tests at the early stage of disease were analyzed in 16 cases of subaeute hepatitis, 4 cases of acute hepatitis with submassive or zonal necrosis but with no serious signs, and 18 cases of classical type of acute hepatitis with spotty hepatic cell necrosis. Loss of appetite and general malaise improved after the appearance of jaundice in 16 of 18 cases of classical acute hepatitis. On the contrary, these symptoms persisted or worsened after the appearance of jaundice in 15 of 16 cases of subacute hepatitis and 2 of 4 cases with submassive necrosis but with no serious signs. A combined abnormality of ZTT and TTT was found in 4 of 5 cases of subacute hepatitis (11 cases were excluded, because the hepatic tests were not performed at the early stage) and all 4 eases of acute hepatitis with submassive necrosis, while it was detected in only 3 out of 18 cases of classical acute hepatitis. The difference of the incidences between the former two groups and the latter one was statistically significant (p<0.01). The cases showing both of abnormal values of ZTT and TTT and no improvement of appetite or general malaise after the appearance of jaundice were 4 of 5 cases of subacute hepatitis, 2 of 4 cases of acute hepatitis with submassive necrosis, and only 2 out of 18 cases of classical acute hepatitis. From these results, it was suggested that most of subacute hepatitis would be possible to diagnose even at the early stage of the disease before the development of severe signs mainly from an analysis of history and liver function tests, especially ZTT and TTT. The diagnosis of acute hepatitis with submassive hepatic necrosis might be also predictable.

Pathology of subacute hepatitis

Histopathological follow-ups by biopsy of 16 cases of severe acute hepatitis were made. Their initial histopathological diagnoses were acute hepatitis with focal necrosis, 3 ; acute hepatitis with zonal necrosis, 2; acute hepatitis with confluent necrosis, 2; early stage of subacute hepatitis, 8 and its late stage, 1. Early stage of subacute hepatitis reveals the young reparative granulation tissue which replaces necrosis taken place during acute hepatitis. In this stage reticulin meshwork of sinusoidal structure remains nearly unchanged. Meanwhile the parenchyma shows beginning of regeneration in small cell groups. In late stage granulation tissue undergoes collagenization and the parenchymal regeneration is advanced. So that apparent scarring and monolobular and multilobular hyperplasia of liver cells are composites. This feature seems that of early cirrhosis. It is found, however, that some follow-up biopsies reveal the feature of chronic hepatitis, active or inactive, with much improvement of lobular architecture. Final biopsy diagnoses of the phase of this study were, healed, 1 ; subacute hepatitis, late, 7 ; chronic hepatitis, inactive, 5; chronic hepatitis, active, 2; and cirrhosis, 1. Histopathological study on the liver in subacute hepatitis previously diagnosed by biopsy was made. Autopsies were performed on the date from 62nd to 171st day from onset of their illnesses. Variegated histopathological appearances were noted, i.e., massive necrosis with only proliferated bile ducts, classical feature of subacute hepatitis, monolobular and multilobular hyperplasia of liver cells with tendency toward cirrhosis.

Subacute hepatitis in our recent experience

We previously reported tha t the values of the ratios of the mesenchymal areas, which were stained in blue in the s taining sections of the liver specimens with azan, to the total areas (M/ T) were all above 17.3% in 17 pat ients of subacute hepatit is diagnosed according to the criteria of Tisdale, and were significantly higher tean those in acute hepatit is or chronic hepatitis. The M/T ratio of the patients died of hepatic coma were all above 71.6% and were significantly higher than those of the survived cases. Severe clinical signs, such as prolonged jaundice, ascites, edema, neurological findings and gastrointest inal bleeding tended to be found more frequently in the cases showing the larger M/T ratios among the survived cases. However, the development of hepatic cirrhosis was not correlated to the area ratios in the initial biopsy specimens. The resul ts indicated tha t the quant i ty of the initial destruction in the hepatocytes was closely related to the fatality or the development of the servere clinical s igns in the relatively early stage. However, the prognosis in the late stage, which means the development of hepatic cirrhosis, may be influenced by the reaction in the host following the hepatocytic destruct ion ra ther than the quant i ty of the hepatocellular damage.

The medical management of peptic ulcer (III)

As methods of the medical management of peptic ulcer, we have studied the process of brief trial of rigid medical management, following the previous report. The total under examination was 78 cases of which males were 70, and the rest was 8 cases of femeles. Their average age were 44. 1. This management was not so effective in the cases of duodenal ulcer. 2. Ulcer scar did not show any effects in this management. 3. Those cases which were effected in this management showed the best look in the process. 4. Many of those which were not effected in the manegement showed UI-IV ulcer or malignant one. From above, we can say that this management efficient as the s tar t ing point of the medical management of gastric ulcer.

Effect of anti-cancer drug on some components of serum in case of gastric cancer

Seventeen amino acids in the serum were determined on pat ients with gast r ic cancer and gastr ic ulcer, and on normal individuals by the chromatographic procedure. In the se rum of pat ients with gast r ic cancer, the amounts of serine, proline, glycine, alanine, valine, leucine and arginine were lower and those of glutamic acid and methionine higher than in normal individuals. Significant differences between postoperat ive gast r ic cancer cases and normal individuals were found for the amino acids serine, g lutamic acid, valine, methionine and hist idine. Between gastr ic cancer and gas t r ic ulcer cases, glycine and arginine levels were lower and meth ionine level was higher in gas t r ic cancer cases. The number of unknown peaks of n inhydr ine positive compounds other than amino acids were also studied. In the serum of gas t r ic cancer cases, significantly more peaks were observed as compared to the normal adults or gas t r ic ulcer patients . Clinical data, especially liver funct ion tes t showed normal . Histology of the l iver was also almost normal .

The medical management of peptic ulcer (II) practical aspect of gastric ulcer at ariga clinic

In order to evaluate the significance of the contraction of tissues at the ulcer base in the healing process of gastric ulcers, we made histological studies of ulcer cases which had been followed up radiologically. We could find that there were often ulcer cases, in which niches had evidently diminished in size but histologically no signs of regeneration of mucous epithelium could be found, therefore, in these cases we can consider that the diminishing process of the ulcers occurred only as the result of contraction of tissues as the ulcer base. The contraction of t issues of this kind was sometimes so noticeable, that the area left which required to be covered with regenerated epithelium was very small. Fur thermore we came across a case with linear ulcer scar, which was considered mainly to have resulted from tissue contraction of a round niche as shown in X ray pictures in its initial stage. The results obtained from these cases proved that 1) only by the contraction of granulation tissues ulcers could decrease in size to such an extent that we could expect real healing before long, and that 2) such a contraction of t issues could account for the formation of linear ulcers.

Brief trial of rigid medical management for gastric ulcer

According to the modified methode of Paust ian, brief t r ia l of rigid medical management was done for the case of gas t r ic ulcer in Ariga Clinic. Those results are as follows; Subjective symptom, occulte bleeding and the feature of gastr ic juice in examined cases of 28 were improved in generaly. Weight decreas ing (1~10%) were seen in all cases. But no significant change of l iver function and findings of se rum biochemistry were seen in examined cases. (25 of gastr ic ulcer) A group: improved 10 cases B group: Improved slightly 6 cases C group: nochange 9 cases operated cases, 7 of C group (gastric cancer 2 of them) In the above study, there is no a definite conclusion. And then it is necessary in the fu ture tha t the follow up of managed case of gas t r ic ulcer must be done continually.