Search

As a link in a series of studies on the effects of blood constituents on the brain function by means of brain perfusion, we used four kinds of artificial blood; namely, the blood containing a low molecular dextran, one containing glutamic acid, one containing essential amino acid group and the one containing both essential amino acid group and glutamic acid. During the perfusion experiments we observed the effects of blood constituents on the function and metabolism of the perfused brain and obtained the following results. 1. When a low molecular dextran is used as the colloid osmotic pressure agent instead of hydrodextran, the amount of the blood flow in the brain is maintained roughly at a certain fixed level throughout the experiment, showing no gradual decreasing tendency. 2. When using the artificial blood supplemented with glutamic acid, EEG of the perfused brain shows an increase in the appearance rate of β32 and β33 bands, approaching closely to the pattern of EEG of unrestrained controls at arousal state. 3. In the case of the blood added with essential amino acids similar to the case using the blood with glutamic acid, EEG approaches towards the alert pattern of the controls. 4. When the perfusion is done with the artificial blood lacking in amino acids, about one hour after the start of the perfusion the amount of glutamic acid and its related compounds in the brain can no longer be maintained at normal level and the decrease, being so marked, brings about a marked decrease also in total amino acid content. 5. When the perfusion blood contains glutamic acid, essential amino acid group or both, the concentrations of amino acids of the brain glutamic acid group and the total amino acid can be maintained approximately at normal level for the duration of over one hour.

A patient with an unresectable hepatocellular carcinoma (HCC) who survived without active treatment 3 years and 8 months after histological diagnosis is described. The size of the liver, which was already quite huge at the time of diagnosis, changed little during the entire clinical observation. However, 2 months before death, his condition deteriorated rapidly following gastrointestinal bleeding due to the direct invasion of the stomach by HCC. A critical reason for the unusually long-term survival of the patient may stem from the facts that a well-differentiated and bile-producing HCC was extent in most encapsulated-tumor tissues and that liver cirrhosis was not present.

The O2- production by neutrophils was examined in 4 cases of refractory anemia with excess of blasts (RAEB) in order to evaluate the possible causes of enhanced susceptibility to infection and to gain some informations on the differentiation of neutrophils in this hematological disorder. In three of the four RAEB cases there was little O2- production by neutrophils, in addition to there being morphological anomalies of the neutrophils such as a Pelger-Huet-like anomaly, granular deficiency and binucleated cells. These results suggest that the impairment of O2- production by neutrophils in RAEB is one of the possible causes of susceptibility to infection and also suggest that the differentiation of neutrophils in this hematological disorder is faulty. The estimation of O2- production by neutrophils may be a useful diagnostic method for preleukemia.

The blood levels of amino acids, ammonia and pancreatic hormones following the intragastric and intravenous administration of a branched-chain amino acid (BCAA)-enriched solution were comparatively investigated in control subjects and patients with liver cirrhosis. There was no essential difference in the time course of serum amino acid and blood ammonia levels between the intragastric and intravenous infusions. Elevation of serum insulin concentrations in cirrhotic patients was significant only immediately after the administration through the enteral route. However, plasma glucagon levels increased similarly when the BCAA-enriched solution was administered through either route. The results indicate that both enteral and intravenous infusions will have similar therapeutic effects on the impaired protein metabolism in cirrhotic patients with protein-calorie malnutrition.

We studied the effect of glycyrrhizin, a compound known as an anti-inflammatory and antiallergic drug, on the membrane permeability change induced by phospholipase A2 (PLA2) and on platelet aggregation. Glycyrrhizin was found to inhibit the PLA2-induced carboxyfluorescein (CF) release from D,L-dipalmitoyl phosphatidylcholine (DPPC) liposomes. Part of this inhibitory effect of glycyrrhizin on PLA2 is accounted for by the physical state of the substrate, the DPPC liposome membrane. Glycyrrhizin also inhibited collagen-induced platelet aggregation in a concentration dependent manner, which may in part account for its inhibitory effect on PLA2.

Direct drain of the cystic duct and drain of the biliary tract through an internal fistula into the duodenum in a 81-year-old man were endoscopically diagnosed without an operation.

Blood ammonia levels in patients with various liver diseases were determined quantitatively by a simple and rapid method using the Amitest Meter System. The results were compared to those obtained by an enzymatic method and were well correlated. This simple Amitest is also useful in animal experiments, particularly when there is a need to determine blood ammonia levels serially. This paper test was evaluated as being accurate and reliable for clinical and experimental use.

The prognoses of patients with alcoholic liver cirrhosis were compared between those who continued to drink and those who stopped. Clinical criteria were strictly set so as to control other variables affecting the prognoses. Four-year survival was significantly higher in the patients who stopped drinking than in those who continued to drink. Continued drinking worsens the prognosis of patients with alcoholic liver cirrhosis.

Increased activities of liver glucose-6-phosphate dehydrogenase (G6PD, EC 1.1.1.49) and 6-phosphogluconate dehydrogenase (6PGD, EC 1.1.1.44) in the pentose phosphate cycle were accompanied with a depletion of reduced glutathione (GSH) following an intragastric administration of carbon tetrachloride (CCl4) to rats. Oxidized glutathione (GSSG) also decreased remarkably, keeping the GSSG: GSH ratio constant. No significant alteration of glutathione reductase (EC 1.6.4.2.), glutathione peroxidase (EC 1.11.1.9) and malic enzyme (EC 1.1.1.40) activities in the supernatant and gamma-glutamyl transpeptidase (gamma-GTP, EC 2.3.2.2) activity in the homogenate of the injured liver were observed. Furthermore, no marked difference in the GSH-synthesizing activity was found between control and CCl4-intoxicated liver. An intraperitoneal injection of GSH produced a significant increase in liver GSH content in control rats but not in CCl4-treated rats; G6PD activity was not affected. Intraperitoneal injections of diethylmaleate resulted in continuously diminished levels of liver GSH without any alteration of liver G6PD activity. In vitro disappearance of GSH added to the liver homogenate from CCl4-treated rats occurred enzymatically and could not be prevented by the addition of a NADPH-generating system. The results suggest that increased G6PD activity in CCl4-injured liver does not play an important role in the maintenance of glutathione in the reduced form and that the decreased GSH content in the injured liver might be caused by enhanced GSH catabolism not due to gamma-GTP.

Electron microscopy of four human T-cell lines revealed the production of type C virus particles in two T-cell lines: one derived from acute lymphoblastic leukemia and the other from a leukemic T-lymphoid malignancy. Virus particles isolated from these cells had reverse transcriptase activity and the major internal structural protein of 30,000 daltons (p30). The indirect immunofluorescence test of these virus-producing cells with sera of patients with adult T-cell leukemia (ATL) was negative. The data indicate that these retroviruses are different from adult T-cell leukemia virus (ATLV).

Serum neutral amino acid levels in cirrhotic patients with abnormal oral glucose tolerance test patterns were not different from those of subjects without impaired carbohydrate metabolism. However, the characteristic features of serum aminograms in the patients, that is, increased levels of tyrosine, decreased levels of valine and leucine and the diminished ratio of branched chain amino acids to phenylalanine and tyrosine levels, were less pronounced in those treated with insulin. This finding is clinically important for evaluating the serum aminogram of cirrhotic patients under insulin therapy.

A new nutritional product (SF-1008C) containing a high proportion of branched chain amino acids (BCAA) and low proportion of aromatic amino acids (AAA) and methionine was tested to see its effect on the impaired protein metabolism and abnormal nutritional state frequently observed in patients with advanced liver cirrhosis. A sharp increase in plasma BCAA levels and fall of AAA and methionine levels were found following the administration of an SF-1008C-supplemented diet to healthy controls and cirrhotic patients, which the BCAA levels increased only slightly following an isocaloric control diet. Blood ammonia levels increased within the normal range transiently following the diets. The SF-1008C-supplemented diet was given for 2 weeks to cirrhotic patients with histories of hepatic encephalopathy, who were taking a low-protein diet because of hyperammonemia. Serum prealbumin levels, nitrogen balance, molar ratio of plasma BCAA/phenylalanine and tyrosine, the number connection test and electroencephalograms improved during the period of the experimental diet. The results, therefore, indicate that a BCAA-supplemented diet is well tolerated by patients with advanced cirrhosis and useful for treatment of impaired protein metabolism. Furthermore, this product is beneficial in preventing hepatic encephalopathy in cirrhotics.

We investigated the antitumor activities of 5-fluorouracil (5-FU), 5'-deoxy-5-fluorouridine (5'-DFUR), 1-hexylcarbamoyl-5-fluorouracil (HCFU) and 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT-207) in combination with hyperthermia in vitro. The antitumor effect of 5-FU (10(-4) M) was slightly enhanced by combination with hyperthermia (42 degrees C) for 2h, and the effect was determined to be additive. Synergistic enhancement of antitumor activity was obtained by the concurrent use of hyperthermia (42 degrees C, 2h) and 5'-DFUR (10(-4) M) or HCFU (10(-5) M). However, the antitumor effect of FT-207 (10(-4) M) in combination with hyperthermia was comparable that of hyperthermia alone. The synergistic enhancement of antitumor activity was not obtained for all drugs when the cells were preheated at 42 degrees C for 2h. On the other hand, when cells were pretreated with drugs before heat exposure, weak interactions were obtained after 5-FU and 5'-DFUR treatment, and a synergistic interaction was obtained after HCFU treatment. It is speculated that the metabolites of 5'-DFUR and HCFU enhance the cytotoxicity of 5-FU, or might change the threshold concentration for a cytotoxic effect of 5-FU in cancer cells.

DNA repair synthesis induced in permeable mouse ascites sarcoma cells by peplomycin, an antitumor antibiotic, was studied. Mouse ascites sarcoma (SR-C3H/He) cells were permeabilized with a low concentration of Triton X-100 in an isotonic condition. Permeable cells were treated with an appropriate concentration of peplomycin to introduce single-strand breaks in permeable cell DNA. DNA repair synthesis in peplomycin-treated permeable cells was measured by incubating the cells with four deoxynucleoside triphosphates in an appropriate buffer system. The DNA repair synthesis was enhanced by ATP and NaCl at near physiological concentrations. More than 90% of DNA synthesis in the present system depended on the peplomycin-treatment. The repair nature of the DNA synthesis was confirmed by a BrdUMP density shift technique. The repair patches were largely completed and ligated in the presence of ATP. Analyses using selective inhibitors for DNA polymerases showed that both DNA polymerase Beta and aphidicolin-sensitive DNA polymerases (DNA polymerase alpha and/or delta) were involved in the repair DNA synthesis.</P>

Immune responses to hepatitis B virus (HBV) vaccine in six low- or non-responded health-care workers were tested with an intradermal low dose (5 micrograms) of the recombinant vaccine. The injection was repeated three or four times at fortnightly intervals. These successive doses of the vaccine induced a high concentration of antibodies with delayed-type hypersensitivity (DTH) skin reactions in all six subjects. A few minor temporary side effects, such as irritation and itching at the injection site, were reported by some of the vaccinees. The results suggest low-dose of intradermal HBV vaccinations for low- or non-responders are safe and readily effective.

We present a case of a primary advanced gastric tumor that was composed of 2 different pathological components: small cell carcinoma and moderately-differentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-differentiated tubular adenocarcinoma components. Therefore, this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection, and has remained in good health, without any recurrences.

Sprague-Dawley rats given azathioprine in the diet for 3 to 4 weeks developed severe liver damage. Elevations of serum alkaline phosphatase and gamma-glutamyl transpeptidase activities were associated with increased hepatic glucose 6-phosphate dehydrogenase levels and decreased liver glucose 6-phosphatase activities, i.e., conditions which were commonly observed in various hepatotoxin-induced liver injuries. Light and electron microscopic observations revealed centrolobular necrosis with large scars and the proliferation of the mitochondria and rough endoplasmic reticulum. This model could be used to study the mechanisms of azathioprine-induced liver damage and its prevention.

An unusual lipoprotein pattern on polyacrylamide-gel disc-electrophoresis was observed in 37 year-old male diagnosed as alcoholic liver injury. The electrophoretic lipoprotein pattern consisted of a major band of pre-beta mobility and minor intermediate, fast-beta and slow-alpha bands. The normal beta band was virtually absent and the alpha band was diminished. The abnormal lipoprotein pattern was observed one week after discontinuing alcohol consumption when marked hypertriglyceridemia demonstrated earlier had already normalized leaving a moderate hypercholesterolemia with reduced esterified cholesterol and abnormal liver function tests. The lipoprotein abnormalities were completely normal one month later. The appearance of a major pre-beta band with normal triglyceride and high cholesterol levels is discussed in relation to the formation of larger triglyceride-rich LDL particles in recovery from alcoholic hepatitis.

The disappearance rates(K) of FT-207 from the blood in patients with primary hepatoma and advanced cirrhosis of the liver were significantly lower than those in control patients with cancer but normal liver function. Pretreatment with tocopheryl nicotinate and indomethacin increased the K values in the control subjects, but was without effect on the K values in patients with primary hepatoma.