Takeo Wada

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.

Elastin--lipid interaction action in the arterial wall. Part 1. Extraction of elastin from human aortic intima.

Elastin was extracted from human aortic plaque and adjacent grossly normal intima by the following methods: (1) 0.1 N NaOH at 100 degrees C, (2) hot NaOH and 0.2 M EDTA, (3) 5 M guanidine--HCl and collagenase, (4) guanidine--collagenase and dithioerythritol--urea--sodium dodecyl sulfate, (5) guanidine--collagenase and EDTA, (6) 10% NaCl and collagenase, and (7) NaCl--collagenase and EDTA. All elastin samples contained small amounts of carbohydrate and hydroxyproline. The lipid content of non-plaque intimal elastin samples was small (2--3%), whereas it increased to 4--6% in plaque intima. The lipid composition of elastin preparations varied significantly with the extraction procedure. Elastin from plaque intima contained significantly more cholesterol (50--60%) and less triglyceride and phospholipid than elastin of non-plaque intima (30--50% cholesterol). The contents of free and esterified cholesterol were comparable in all preparations. The main phospholipid in all samples was sphingomyelin, which comprised between 50 and 80% of the total phospholipid. Compared with NaOH-purified elastin, the other elastin samples were characterized by an increased phosphatidyl--choline content, while they all contained an almost equal amount of phosphatidylethanolamine. In elastin samples from plaque intima, the polar amino acids were increased, whereas cross-linking amino acids were decreased. The polarity and hydroxyproline content of elastin samples were slightly decreased after treatment with EDTA or dithioerythritol--urea--sodium dodecyl sulfate.

Elastin—lipid interaction in the arterial wall part 2. In vitro binding of lipoprotein-lipids to arterial elastin and the inhibitory effect of high density lipoproteins on the process

The mechanism of lipoprotein binding to arterial elastin, and the inhibitory effect of high density lipoprotein (HDL) on the in vitro complex formation between plasma low density lipoprotein (LDL) and elastin were studied. The binding of LDL-cholesterol, phospholipids and triacylglycerols to delipidated elastin increased progressively with time over 24 h of incubation. The results of a kinetic study on lipoprotein-cholesterol concentration in the incubation medium, suggesting that the ability to bind cholesterol to elastin decreases in the following order: very low density lipoprotein (VLDL), LDL, intermediate density lipoprotein (IDL) and HDL, and that the capacities to bind to a fixed amount of elastin decrease in the order: LDL, IDL, VLDL and HDL. When a definite amount of LDL was incubated with elastin in the presence of increasing concentrations of HDL, the binding of lipids to elastin progressively decreased. On the other hand, no release of cholesterol, bound to elastin during preincubation with LDL, could be detected in additional incubations with HDL, apoHDL or apoHDL-phospholipid complex.

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.

CLINICAL SIGNIFICANCE OF α2H‐GLOBULIN

: Incidences of alpha2H were investigated in sera from patients with various malignant and nonmalignant diseases. With counterimmunoelectrophoresis, alpha2H was detected in a wide variety of neoplastic diseases, and also in nonmalignant hematological disorders. Diagnostic significance was described regarding primary hepatoma and acute myelogenous leukemia. Factors affecting alpha2H levels in sera were also discussed in relation to the neoplastic and nonneoplastic disease process.

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.

Secretin secretion in patients with duodenal ulcer, chronic pancreatitis and diabetes mellitus.

SummarySecretin releasing response to intraduodenal acid infusion was investigated in 15 cases of diseased control, 7 cases of duodenal ulcer, 5 cases of chronic pancreatitis, and 6 cases of diabetes mellitus.Plasma secretin levels in response to duodenal acidification were less in duodenal ulcer and the appearance of the maximal peak was delayed compared with that found in control. It is suggested that the secretin release was impaired in duodenal ulcer in spite of hypersecretion of gastric acids.In chronic pancreatitis, secretin releasing response to acidification was markedly impaired, in addition, inhibition of secretin release by bicarbonate was diminished due to a lack of bicarbonate flow from the pancreas. On the other hand, although the response of secretin release in diabetes mellitus was also lower compared with that in control group, the capacity of secretin response showed values in-between control subjects and chronic pancreatitis.This research was supported in part by grant from the Ministry of Education, Science and Culture in Japan.

Studies on the CEA-like substance in gastric juice.

SummaryConcentration and heterogeneity of CEA-like substance in gastric juice were studied using radioimmunoassay. Statistically significant increase of CEA-like substance in gastric juice was found in advanced atrophic gastritis (P<0.01), early gastric cancer (P<0.05) and advanced gastric cancer (P<0.01) as compared with normal subjects.In cases with atrophic gastritis with a high degree of intestinal metaplasia, the concentrations above 300µg/dl were noticed. The results indicate that increased concentrations of CEA-like substance in gastric secretions may strongly suggest the presence of a marked intestinal metaplasia and/or cancerous changes of gastric mucosae, including the early cancer.The distribution of CEA activity in gel filtration fractions of gastric juice was compared using kits of two different radioimmunoassay systems. The patterns of CEA activities were different between the two different kits used, but the main peaks were located in the fractions with the molecular weight of 20X104 daltons corresponding to that of serum CEA. It is considered, however, that the CEA-like substance in gastric juice specimens may be more or less heterogenous when any of the methods is used.

Serum gastrin and gastrin-like immunoreactivity of gastrointestinal mucosa in fetal, neonatal and adult rats

SummarySerum gastrin concentration became detectable in rats at one week after birth (56 pg/ml), and a rapid rise to 198 pg/ml was seen at two weeks after birth. Gradual decreases were seen again at three weeks and four weeks, and thereafter it attained the adult level of 132 ± 17.6 pg/ml.In regards to the gastrin-like immunoreactivity (GLI) in the gastrointestinal mucosa during the fetal period, the values were extremely low even in the antral mucosa. However, the GLI showed an increase during the neonatal suckling period, and was accompanied by a remarkable increase at the commencement of feeding.This GLI coincided with so-called little gastrin, and while an increase accompanied by the development of growth was seen, no qualitative changes were evident. GLI values were high in the duodenal mucosa followed by the antrum, and positive evidence was also seen in the corpus of the stomach and jejunum. High values of GLI in the mucosae were gradually seen at two weeks after birth coinciding with the rise in serum gastrin levels, and the significance of the increases was discussed from the angle of the trophic effect of gastrin.

An epidemiologic study of australia antigen with special reference to incidence in medical and paramedical personnels

High incidence of hepatitis in hospital personnels has been frequently reported. Of patients with acute hepatitis admitted to this Depar tment during the past 8 years, 25.7% were hospital staffs, and similarly, 24.7% of patients registered at the Hepatology Out-pat ient Clinic were medical and paramedical staffs. In view of the possible close connection between Australia antigen (Au) and hepatitis virus, an epidemiologic study of Au was carried out, with stress laid on the incidence of Au in personnels of medical institutions. Serum samples were obtained from 435 9 volunteers who were medical and paramedical staffs in Hokkaido district, and who had no history of hepatitis. Of a total of 64 subjects who work in hemodialysis units in 5 institutions, 6 were found to have Au, and 2 were found to have antibody (Ab) against Au, so that a total of 8 subjects (12.5%) showed contamination with Au. In one of the 5 institutions, Au was detected in 10 of 154 personnels tested, and 3 out of the 10 were hemodialysis unit personnels. In another of the 5 institutions, Ab was detected in 3 of 57 nurses, and 2 of the 3 Ab-carriers were hemodialysis unit personnels. The over-all incidence of Au and Ab in medical and paramedical staffs in these 5 institutions was approximately 5%, which was significantly higher than the estimated incidence of approximately 1% in the general population of the district. O f 200 laboratory technicians working in a number of hospitals in Hokkaido, Au was detected in 11 subjects, and Ab was found in 1, so that a total of 12 subjects (6.0%) were contaminated with Au. I t is concluded that the incidence of Au and Ab in medical and paramedical staffs are significantly higher than the incidence in general population, and hemodialysis unit personnels and laboratory technicians are especially subject to contamination. Countermeasure to this problem appears urgent.