A radioimmunoassay (RIA) was developed for carboxyterminal peptide of human type I procollagen (PIC) purified from culture medium of human fibroblasts. Serum PIC levels were studied by this assay in 39 normal healthy volunteers, in 30 patients with gastric cancer and in 9 patients with gastric ulcer. The aminoterminal peptide of type III procollagen (PIIIN) levels in those sera were also studied by RIA-kit (Hoechst). Serum PIC and PIIIN concentration of normal subjects were 42±19ng/ml and 10±1ng/ml respectively. Abnormal elevation of serum PIC level (cut off level, 80ng/ml) was observed in 8 out of 14 patients with scirrhous carcinoma of stomach (mean, 102±56ng/ml). However, sera from patients with other histological types of gastric cancer and gastric ulcer had normal value of PIC. Serum PIIIN levels elevated slightly in the patients with scirrhous carcinoma of stomach as well as other histological types of gastric cancer. Serum PIC levels paralleled well the clinical course of the patients with scirrhous carcinoma of stomach. These results suggest that measurement of serum PIC provide a new means for the diagnosis and monitoring therapy of the scirrhous carcinoma of stomach.
Human jejunum was perfused with an electrode-attached double lumen tube, and potential difference change was recorded during changes of NaCl concentration of perfusate. Measuring the half time of potential difference change from this recorded curve, the functional unstirred water layer thickness was calculated by Diamond formula. The mean value of this thickness was 247.9±50.6 (SD) μm in 28 patients.
Antibody-dependent cell-mediated cytotoxicity (ADCC) toward sheep red blood cells by peripheral blood mononuclear cells was modulated by pretreatment of effector cells with sex hormons: When peripheral blood mononuclear cells were pretreatmented with a given dosis of estrogen, the lysis of erythrocytes via ADCC reaction was enhanced significantry and this enhancement was suppressed by testosterone. A similar effect of sex hormone on ADCC reaction was also demonstrated when silicatreated mononuclear cells were used as a effector. Furthermore, although a excess of estrogen did not alter effector activity, simultaneous addition of low dosis of testosterone was shown to increase in ADCC reaction. These results suggest a possibility that sex hormones may not only modulate immune responses but also give some effect on ADCC reaction.
The T cell subsets in liver biopsy specimens of patients with chronic hepatitis were studied with monoclonal antibodies (Leu series) using the immunoperoxidase method (PAP). For specimens of chronic active hepatitis (CAH) Leu 2a positive cells in areas with piecemeal necrosis were predominant and there was no significant difference among type B, type NANB and autoimmune type of CAH. The number of Leu 2a positive cells in portal area of autoimmune type were fewer than those of types B and NANB of CAH. Therefore, it is suggested that the decrease of suppressor T cell population may be related to the pathogenesis of autoimmune hepatitis. To investigate the difference between type B-CAH and type B-chronic inactive hepatitis (CIH), the type of infiltrating T cell in portal areas was examined. The rate of Leu 4 and Leu 2a positive cells in portal areas in type B-CAH was lower than that of type B-CIH. Therefore, it is suggested that the suppressor T cell system may play an important role to activate the killer T cell in CAH.
To determine the hepatic gluconeogenesis from amino acid in chronic liver disease, blood glucose with other parameters indicating level of blood glucose control, such as glucagon, insulin were measured after L-Alanine administration in 11 cases of hepatocellular carcinoma (HCC), 18 cases of decompensated liver cirrhosis (LCD), 16 cases of compensated liver cirrhosis (LCC), 18 cases of chronic active hepatitis (CAH), and 10 cases of normal controls (NC). Thirty to 180 minutes after L-Alanine administration; 1) Blood glucose levels declined in HCC and LCD, whereas elevated in LCC, CAH and NC. 2) Plasma glucagon increased, whereas serum insulin decreased both in HCC and LCD, indicating enhancement and suppression of secretary function in A-and B-cells of islet, respectively. 3) Serum alanine and blood lactate levels were significantly higher in HCC and LCD than in other three groups, 90 to 180 minutes after L-Alanine administration. In conclusion, in the groups of HCC and LCD with extensive hepatocellular dysfunction indicated impairment of alanine utilization for gluconeogenesis.
Postprandial changes of portal blood flow have been measured quantitatively by an ultrasonic pulsed Doppler flowmeter combined with a B-mode scanner. Ten healthy volunteers, ten patients with chronic active hepatitis and ten with cirrhosis were measured. Contents of the test meal were as follows; protein: 8Cal%, fat: 22Cal%, carbohydrate: 69Cal%, and water: 77gm%. The amount of the test meal loaded on patients and healthy volunteers was 10Cal/10ml/kg body weight. Blood flow volume of the portal vein, before feeding, was as follows; healthy volunteers: 1, 007± 322ml/min, chronic active hepatitis: 757±245, cirrhosis: 891±357ml/min. Blood flow volume was increased, 1 hour after feeding, in all groups, and the average increased blood flow rates were as follows; healthy volunteers: 77%, chronic active hepatitis: 47%, cirrhosis: 26%. Postprandial changes of portal blood flow are 30 to 50 percent less in patients with chronic liver diseases than in healthy volunteers. Postprandial changes of splenic venous blood flow are as follows; 28% in healthy volunteers, 9% in chronic active hepatitis and 9% in cirrhosis. Consequently it is believed that the marked increase of portal blood flow, after feeding, is due to the increase of intestinal blood flow.
It is well known that lysyl oxidase plays a very important role in cross-linking of collagen and elastin. However we can't find any available reports about the enzyme activity in man. We succeeded to measure the plasma activity in cases with liver disease with the method of 3H2O release assay using 3H-lysine-labelled collagen as substrate. The activity showed significantly high in alcoholic liver disease (p<0.01), primary biliary cirrhosis (p<0.01) and non-alcoholic liver cirrhosis (p<0.05) against normal subjects. The plasma activity of a case with alcoholic hepatitis altered in parallel to the degree of hepatic fibrosis after admission. The measurement of plasma lysyl oxidase activity is useful assessment for the hepatic fibrosis in a different sense from the measurement of prolyl hydroxylase or procollagen peptide.
The acute effect of ethanol administration on in vivo hepatic tissue oxygenation and hepatic hemodynamics was examined in rats treated chronically with CCl4 using organ reflectance spectoro-photometer and thin needle oxygen electrode. In rats treated chronically with CCl4, the hepatic tissue PO2 was lower (5mmHg) than that of normal rats (23mmHg), and the regional hepatic blood volume (ΔEr 569-650), oxygen saturation of hepatic blood hemoglobin (SO2) and in vivo hepatic oxygen consumption (VO2) were respectively 86%, 72%, 82% of normal rats. After administration of ethanol via gastric tube (1g/kg BW.), the hepatic tissue PO2 in normal rats increased, concomitantly with the increase of ΔEr 569-650 and VO2. By contrast, in rats treated chronically with CCl4, the hepatic tissue PO2 did not increase and the increase of hepatic blood volume did not compensate the increase of hepatic oxygen consumption.
3H-thymidine autoradiograpgical study was performed upon the pancreas during N-nitrosobis (2-hydrxypropyl) amine-induced carcinogenesis in Syrian golden hamsters. The results are shown as follows: It was generally observed that the percentage of the labeled unclei (labeling index) increased as the dysplastic grade increased. The dysplastic lesions with multilayered cells (grades III and IV) showed transient increases in labeling index between 7th to 10th day. Among the lesions with multilayered cells, labeling index was higher in monolayered cells (C group), which were directly contacting with basement membrane, than in other cells groups (A and B groups). Persistant decreases in labeling index were seen in C group after 3H-thymidine administration, whereas transient increases between 5th to 10th day was observed in A and B groups. In C group, the number of grains in labeled nuclei decreased more earlier and more remarkably than in A and B groups. From these results, it is suggestive that the unilayered cells contacting with basement membrane may play the proliferative center in the dysplastic lesion and have an invasive potency afterwards.
Syrian golden hamsters were given weekly injections of the pancreatic carcinogen N-nitrosobis (2-hydroxypropyl) amine for up to 20 weeks. The carcinogenic process of the pancreas induced by this treatment was studied by light and electron microscopy, and changes of cell surface and cytoplasmic saccharides were examined by a battery of 9 lectin horseradish peroxidase conjugates, with special attention to the pseudoductular structures. The development of the pseudoductules preceded that of hyperplasia of ductal epithelium, and when hyperplasia of ductal epithelium appeared, highly dysplastic ductular proliferations had already been observed. This fact indicates that pseudoductules are preneoplastic in nature. On electron microscopy, some of the pseudoductules were found to consist of intermediate acinar-ductular cells, which had zymogen granules and rough endoplasmic reticula with reduction in number, raising the possibility that dedifferentiated acinar cells might be involved in the histogenesis of the pseudoductules. The results of lectin-horseradish peroxidase conjugate stainings indicated that L-fucose-containing glycoconjugates are abundant on pseudoductular cells, and L-fucosecontaining and N-acetylgalactosamine-containing glycoconjugates are abundant on malignant cells suggesting that acinar cells might aquire these phenotypic characteristics during their dedifferentiation and malignant transformation.