Mechanism of elevation of serum indirect bilirubin was investigated clinically and experimentally with special regard to p-glucuronidase activity. In clinical cases of obstructive jaundice. 1) Ratio of serum direct bilirubin to indirect one was about 7: 3. 2) Serumβ-glucuronidase activity w as higher (within 4.5 times) as compared to controls. In bile duct-ligated rats. 1)β-glucuronidase activity in serum was higher (within three times) than that of controls. 2)β-glucuronidase activity in liver tissuewas positively correlated to that of serum. 3) In the beginning of the ligature, lysosomalβ-glucuronidase activity was elevated, followed by parallel increase in hepatic β-glucuronidase activity and in serum indirect bilirubin, simultaneously reaching to each peak. 4) Maximal fragility of lysosomal membranes was observed on the fifth day after the ligature in accordance with the peak of serum bilirubin level. Above mentioned facts seem to indicate a substantial role of A-glucuronidase in liver by which deconjugation ofdirect bilirubin is catalyzed.
We have already reported that, in the skin test using human fetal colon LPS (lipopolysaccharide) as antigen, patients with IBD (inflammatory bowel disease) frequently showed immediate reaction for the antigen. In the present study, we have studied whether or not this antigen has the capacity of delayed type reaction in the skin test, and obtained the following result that the antigen could show delayed reaction in several cases of IBD. At the same time, the same antigen could show the positive result in LMT (leukocyte migration inhibition test) in several cases of IBD, though the frequency of positive results is lower thanthe skin test. Judging from these results, it may be concluded that human fetal colon LPS may have the capacity (antigenicity) of cellular immunity as well as of humoral immunity and it may be necessary to perform the precise molecular analysis of the antigen.
Nineteen surgical specimens of ulcerative colitis were studied histopathologically on distribution of lesions. And variation in number of endocrine cells was analysed on active andinactive phase, and clinical duration. Widespread ulcers were most commonly observed in the transverse and left-side colon. Ulcer scars were observed in both active and inactive phase. The ulcer scars suggest remission and relapse of ulcerative colitis. Crypt abscesseswere observed in most parts of the colon, and concomithant finding of goblet cell depletionsuggested decrease of resistance of mucosa. Inflammatory polyps were observed in 17 cases.Marked mucosal atrophy was prominent in cases with clinical duration over 1 year. Paneth cell metaplasia was observed in 16 cases especially in the righ.t-side colon. Significant decrease in number of endocrine cells was observed in active lesions and in cases with clinical duration under 1 year, but was not observed in inactive lesions nor cases with clinical duration over 1 year.
The cytology of the bile, which was aspirated from the intrahepatic duct during percutaneous transhepatic cholangiography, was examined for a difinitive diagnosis of malignant diseases of the biliary tract. 57 cases were examined by cytology and correct diagnosis were made on 40 cases. Cytologic diagnosis of 40 cases were assertained by histopathological diagnosis by autopsy or surgical specimens. positive cytodiagnosis were obtained in 25 (68%) among 37 malignant cases and negative cytodiagnosis were obtained in 15 (75%) among 20 benign cases. Especially, in cancer of the common bile duct, 9 (90%) of 10 cases were positive and 4 cases were operable with small tumors. Morphological study of cells was performed for the correct cytologic diagnosis of the bile. Namely, characteristics of benign atypical cells of the gallbladder were analyzed, and differences from cancer cells of gallbladder were examined. Morphological differences of cells, obtained by touch smear and exfoliated cells in the bile from patients with benign or malignant disease, were studied. The result of these analysis is usefull for distinguishing the false positive and falsenegative and is helpfull for accurate diagnosis.
It is well known that acute gastric mucosa' lesions are frequently occurred shortly after the events in patients under “stress state” and that these lesions are mainly found in thecorpus of the stomach. The authors attempted to clarify these clinical characteristics, and investigated biochemically the aerobic energy metabolism in the fundic gland mucosa and antral gland mucosa in animals and humans. In rats and rabbits, the rate of oxygen consumption with and without added substrates and the concentration of the respiratory enzymeswere about three times higher in the fundic mucosa than in the antral mucosa in homogenateas well as mitochondrial fraction. In the human stomach, it was also shown that the fundicmucosa showed a significantly higher concentration of the respiratory enzymes, the amount of which was proven to be in a linear correlation with the oxygen consumption rate of aerobic organs. These differences in the aerobic energy metabolism was not due to a qualitative difference in the mitochondrial function. From these observations, it seemslikely that the integrity of the structure and function of the fundic gland mucosa dependson bloodsupply more significantly than those in the antral gland mucosa. Hence it is suggested that the fundic mucosa may be more susceptible to the shock- or stress-induced local circulatory insufficiency.
By using coil planet centrifuge system, hemolysis end points (maximal osmotic resistance) of erythrocytes in sodium chloride solution were determined in hepato-biliary diseases. Hemolysis end points were shown to shift to lower osmotic pressure in hepato-biliary diseases, especially in malignant obstruction, chronic aggressive hepatitis II B and decompensated liver cirrhosis. Osmotic pressure at end point correlated significantly with the resultsof cholinesterase, normotest, prothrombin time, indocyanine green loading test. Osmoticpressure at end point correlated inversely with cholesterol content of erythrocytes, ratioof cholesterol to phospholipid of erythrocytes and a-lipoprotein fraction, and positively with a-lipoprotein concentration and lecithin cholesterol acyltransferase (LCAT) activity of plasma. After incubation of erythrocytes in plasma samples LCAT activity of which had been inhibited by either addition of deoxycholate in different concentration or heat inactivation, hemolysis end point shifted to lower osmotic side and cholesterol content of erythrocytes increased according to the degree of inhibition of LCAT activity. Incubation oferythrocytes in heat inactivated plasma enriched with cholesterol by addition of cholesterol emulsion resulted in much greater change of the same trend. The increment of maximalosmotic resistance of erythrocytes is proportional to the increase of cholesterol in erythrocyte membrane which is a reflection of reduced uptake of cholesterol by a-lipoprotein caused by decreased activity of plasma LCAT in these patients.
A method of fluorometric determination of serum bile acid using 3α-hydroxysteroid dehydrogenase was investigated. Bilirubin or other unknown contaminants remained in serumextract was proved to absorb the excitation light (wave length 350nm) and also the emission light (wave length 460nm), resulting up to 30% decrease of expected fluorescence intensity depending on the amount of contaminants remained. As the degree of these interferences differed from one sample to another, we determined recoveries of bile acid in extraction procedure as well as those of fluorescence separately, the latter being obtained by adding a NADH standard solution to each serum extract. The range of serum bile acid concentration in normal subjects was found to be 6±5μM (mean±SD), which was slightly higher than that of previous reports. Increased serum bile acid concentrations were observed in primary biliary cirrhosis, acute hepatitis (florid stage), liver cirrhosis, drug induced hepatic injury, acute hepatitis (convalescent stage) and chronic hepatitis (active form), in decreasing order. In 3 observed cases of acute viral hepatitis, the serum bile acid concentration did not necessarily decrease prior to the serum bilirubin level. In acute hepatitis, serum bile acid concentration correlated with GOT and GPT levels (r=0.91 and 0.91, respectively) in florid stage and with ALP, LAP andγ-GTP (r=0.97, 0.95 and 0.86, respectively) in convalescent stage. A low-grade negative correlation coeffIcient was obtained between serum antipyrine half life and serum bile acid level in normal subjects.
With CDCA administered orally for a week consecutively in rats and clinical cases, its effects on the capacity of cholesterol solubility and the liver were studied. In 4 groups of rats, CDCA was given at doses of 3mg/kg, 10mg/kg, 50mg/kg, and 100mg/kg, per day respectively. In 3 groups of clinical cases, doses were 250mg, 750mg, and 1, 500mg, per day respectively. Either in rats or in clinical cases, the given doses caused no significant changes in biliary cholesterol and phospholipid levels. Total bile acids levels were increased significantly in rats given doses of 3mg/kg and 10mg/kg. In clinical cases, total bile acids presented highest increase in the group with 250mg, followed by the group with 750mg, whilethey were decreased in the group given the largest dose of 1, 500mg; cholesterol holding capacity was accordingly most prominent in the group with 250 mg. Cholesterol holding capacity, seen in the dose of CDCA per kg of body weight, was greatest in one with 6.3 mg/kg, followed by another with 12mg/kg. The rat liver revealed no distinct changes in light microscopic examination, but electronmicroscopically unusual findings such as swellings of mitochondria was demonstrated in the groups given more than 10 mg/kg. In clinical cases, only one cases in the group with 750 mg showed a transient rise in S-GOT and S-GPT.
A 77-years old man admitted to our hospital, complaining of abdominal distension and dull epigastric pain. Fluoloscopic and endoscopic examination of the stomach, he was diagnosed of cancer of the stomach.(Borrman III), Adenocarcinoma. He had been treated with only anticancer drugs, because of old age and his anxiety for the operation. However, he was getting worse gradually and suffered from a severe pain on the cervical region, a few days before his death. His post-mortem examination revealed gastric cancer metastase to the pancreas and parotitis. During his course, his serum amylase isozyme pattern changed to pancreatic dominant pattern from normal, then to carotic dominant pattern. This case suggests the possible organ relationship between the pancreas and the parotis from the view point of amylase isozyme.
Isoenzymes of alkaline phosphatase (ALP) are usually normal in the serum of acute viral hepatitis. We discovered a case of acute hepatitis who had an abnormal ALP isoenzyme in blood. This isoenzyme migrated more toward cathode than intestinal ALP by electrophoretic separation of isoenzymes. Enzymologic natures of this isoenzyme were similar to those of normal hepatic isoenzyme on inhibition by L-phenylalanine, L-homoarginine and L-leucine. This isoenzyme was detected in the liver extract also. Decrease in electrophoretic mobilities ofisoenzymes was seen both in hepatic and abnormal ALP by neuraminidase digestion, but retardation rate was more scarce in abnormal ALP. These data indicate that this isoenzyme is made by the liver which exhibits abnormal metabolism.