PubMed Health⌕ Search

Biomedical subjects

J Kojima

Publications and source records attributed to J Kojima.

At least 91 records · Page 5Linked to original sources
PubMed1987

Glycylproline dipeptidyl aminopeptidase and gamma-glutamyl transpeptidase in human hepatic cancer and embryonal tissues.

Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities and their subcellular distributions were compared in human hepatic cancer and embryonal tissues. The activity of GPDA in cancer tissues was significantly higher than that found in healthy liver, though there were no significant differences between fetal and adult livers. The placenta, however, had the highest GPDA activity. The activity of gamma-GTP, on the other hand, was increased significantly not only in cancer tissues but also in live tissues adjacent to the tumor, and it was higher in the fetal liver but much lower in the placenta. Subcellular distribution of GPDA was also different from that of gamma-GTP in cancer tissues, especially after postmortem changes. These results suggest the possibility that GPDA has carcinoembryonic characters similar to gamma-GTP, but the mechanisms, whereby serum activities of these two enzymes were increased in hepatocellular carcinoma patients, are different from each other.

Adult↗
PubMed1987

[Evaluation of immunochemotherapy in patients with primary liver cancer. Osaka Research Society for Liver, Gallbladder and Pancreas].

The effectiveness of BRM (biological response modifier) for primary liver cancer was investigated in a prospective randomized and well controlled study. The protocol consisted of 3 groups: 1) Tegafur oral administration only, 2) OK-432 i.v. plus Tegafur, and 3) PSK oral application plus Tegafur. One hundred seventy-two Japanese patients were entered. The results revealed that BRM addition was more effective than Tegafur therapy alone with regard to tumor regression and the results of clinical examinations, but that there was no difference in subjective symptoms between the use of BRM and the other regimes. As to prognosis, patients given PSK survived longer than those given Tegafur alone, but OK-432 group had the same survival rate as the other two groups as a whole. The relationship among the three groups with regard to survival time, was similar to that of their respective total efficacies. Between the three groups, there was a significant difference in the incidence of adverse effects. The difference was sustained with the occurrence of fever symptoms as a result of OK-432 stimulation, with and BRM therapy decreased the gastro-intestinal side effects in comparison with the control group.

Adult↗
PubMed1985

Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent. II. Influence of the route of administration on bioavailability in dogs.

The pharmacokinetic parameters of nipradilol (NIP), a new potent antihypertensive and antianginal agent, and propranolol were determined after oral, intravenous and intraportal administration to the beagle dog implanted with cannula in portal vein at a dose of 1 mg/kg. Orally administered NIP underwent extensive first-pass metabolism leading to low bioavailability (11%), despite of complete gastrointestinal absorption. On the constant infusion for 30 min into the portal vein, hepatic extraction ratio was 0.71. The reduction in the systemic availability of orally administered NIP could partly be attributed to the fact that denitration and glucuronidation of NIP occur primarily in the intestinal tract and liver, respectively. Following oral administration of NIP, smaller amount of unchanged drug (1.9%) was excreted into the urine than that of intravenous administration (5.8%). However, in the qualitative and the quantitative aspects on urinary metabolic patterns, there was no appreciable influence of the route of administration. On the other hand, the systemic availability and the hepatic extraction ratio of propranolol were 11% and 0.86, respectively, suggesting that the first-pass metabolism through the liver actually contributes to the reduced availability.

Administration, Oral↗
PubMed1985

Pharmacokinetics of nipradilol (K-351), a new antihypertensive agent. I. Studies on interspecies variation in laboratory animals.

The pharmacokinetics, plasma protein binding and metabolism of nipradilol (K-351: NIP), a new potent antihypertensive and antianginal agent, were compared in dogs, monkeys, rabbits and rats. In all species studied, NIP did not appreciably bind plasma protein (less than 30%) and was extensively distributed in tissues. There was a good correlation between the volume of distribution at steady state (Vss, 1) and body weight (B, kg) of the animal species as follows: Vss = 4.42 B0.805. In addition, Vss increased as a function of the plasma free fraction. Intrinsic clearance of unbound drug (CLuint, 1/h) also correlated with body weight as follows: CLuint = 4.78 B0.722, but blood clearance in rabbits exceeded hepatic blood flow, suggesting extrahepatic metabolism. Following oral administration, the systemic availability for all species increased with the oral dose, while the half-life was about 2 h, and was independent of dose. The apparent threshold dose (ATD, mg/kg) was observed to vary inversely with body weight of the animal species as follows: ATD = 4.33 B-0.472. Less than 2% of the dose was excreted into the urine as unchanged NIP in all species. The metabolic profile for all species was similar, but pronounced quantitative differences among species was observed for aliphatic and aromatic hydroxylation of the 3,4-dihydro-2 H-1-benzopyran ring.

Administration, Oral↗
PubMed1983

[Clinical study on combination chemotherapy of primary liver cancer].

Three regimens were comparatively studied by a randomized trial in 95 patients with hepatic, biliary or pancreatic carcinomas: Group 1; Futraful (FT) alone, Group 2; FT plus cyclophosphamide (Ex), and Group 3; FT plus Carboquone (CQ). There was no difference in overall response rate among the three groups, evaluated by three valuables, i.e., improvement of subjective symptoms, improvement of laboratory examinations, and regression of the tumor. Group 2 demonstrated a favorable result in regression of the tumor as compared with other groups. In cases where the improvements of subjective symptoms and laboratory examinations were observed, the survival duration was prolonged, but in cases of the tumor regression, the survival was not prolonged. The improved survival rate was observed in Group 1, but neither in group 2 nor 3. There was no difference in the frequency of hematotoxicity among three groups (the frequency was as low as 3.4-8.8%). The frequency of side effect in subjective symptoms was 22% for the Group 1, 68% for the Group 2, and 62% for the Group 3, respectively.

Adult↗
PubMed1982

Glycosaminoglycans in 3'-methyl-4-dimethylaminoazobenzene-induced rat hepatic cancer.

The changes in glycosaminoglycans in livers of rats with 3'-methyl-4-dimethylaminoazobenzene-induced hepatic cancer were examined and compared with those in fetal liver. The incorporation of 35S into sulfated glycosaminoglycans in hepatic cancer tissue was also studied after i.p. injection of Na(2)35SO4. The major component of glycosaminoglycans in healthy adult rat liver was heparan sulfate (61.7%), with hyaluronic acid (21.1%), dermatan sulfate (13.1%), and chondroitin sulfate (4.0%) as minor components. The quantities of all of the examined glycosaminoglycans were higher in tumors than in normal liver, but chondroitin sulfate and hyaluronic acid were more prevalent in the tumors (about 51 and 7 times higher, respectively). As a result, the share of heparan sulfate was decreased (37.1%) in the tumors. The high content of chondroitin sulfate (about 30 times) and the decreased share of heparan sulfate (29.0%) were also observed in fetal liver. The incorporation of 35S into individual glycosaminoglycans varied markedly. Approximately 90% of the label in glycosaminoglycans of healthy liver was found in a heparan sulfate fraction 4 hr after injection. In hepatic cancer tissue, however, 35S incorporation into both chondroitin sulfate and dermatan sulfate fractions was increased about 6.5- and 5.6-fold, respectively, of those in healthy liver.

Adenoma, Bile Duct↗
PubMed1981

Changes in charge density of heparan sulfate isolated from cancerous human liver tissue.

Heparan sulfate fractions were isolated from three normal human livers and three cancerous human liver tissues, and their polyanionic properties were examined using electrophoresis, sequential partition fractionation, and chemical analyses. More than 60% of total glycosaminoglycans from normal human liver and about 30% from cancerous liver tissue were found to be heparan sulfate from their resistance to exhaustive digestion with chondroitinase ABC and their susceptibility to nitrous acid treatment. The heparan sulfate isolated from cancerous liver tissue afforded a lower sulfate/uronic acid molar ratio (0.58 to 0.65) than did normal human liver heparan sulfate (0.76 to 0.80). Also, the former showed lower electrophoretic mobility in 0.1 M HCl and a different partition fractionation profile in comparison with the latter. These differences in charge density of the macromolecule were not detected on the chondroitin sulfate and/or dermatan sulfate fractions isolated from normal human liver and cancerous liver tissue.

Chemical Fractionation↗
PubMed1980

Serum and liver glycylproline dipeptidyl aminopeptidase activity in rats with experimental hepatic cancer.

Changes of glycylproline dipeptidyl aminopeptidase (GPDA) and gamma-glutamyl transpeptidase (gamma-GTP) activities were compared in the serum and liver tissue of rats with hepatic cancer induced by 3'-methyl DAB. Serum glycylproline dipeptidyl aminopeptidase activity in rats with the azo dye-induced hepatic cancer was significantly higher than that in healthy rats, but the increase was not so extensive compared with that of gamma-glutamyl transpeptidase. The specific activity of glycylproline dipeptidyl aminopeptidase was decrease in the microsomal fraction and increased in the supernatant fraction of hepatic cancer tissue, whereas that of gamma-glutamyl transpeptidase was increased in both microsomal and supernatant fractions. These results suggest that the mechanisms, whereby serum activities of these two enzymes were increased in rats with hepatic cancer, were different from each other.

Aminopeptidases↗
PubMed1980

Electrophoretic fractionation of serum gamma-glutamyl transpeptidase in human hepatic cancer.

Serum gamma-glutamyl transpeptidase from patients with various hepatobiliary diseases was fractionated by polyacrylamide gradient gel slab electrophoresis to study the specific patterns of gamma-glutamyl transpeptidase fractions in hepatic cancer. On zymograms of normal serum gamma-glutamyl transpeptidase, a total of 10 fractions was observed. Additionally, fractions I', I" and II' were recognized in sera from hepatocellular carcinoma patients. Among these, fraction I', which migrated slightly, but significantly, slower than fraction I was the most specific; it was found in 55% of the hepatocellular carcinoma patients. Fractions I" and II' were also relatively specific, each was observed in about 29% of these patients. Fractions V to IX were observed in few hepatocellular carcinoma cases. Fraction I' is thought to be a hepatoma-related fraction, highly specific for the serum of hepatocellular carcinoma patients. Fractions I" and II' were also thought to be hepatoma-related fractions of gamma-glutamyl transpeptidase. We suggest that fractions I', I" and II' may be useful in the diagnosis of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗
PubMed1980

Changes in the cellular glycosaminoglycans of cultured mastocytoma cells induced by sodium butyrate.

The effect of sodium butyrate on the cellular glycosaminoglycans of cultured mastocytoma p-815-4 cells was investigated using enzymic digestion, electrophoresis, nitrous acid degradation, and sequential partition fractionation. The average cellular glycosaminoglycan content of mastocytoma p-815-4 cells grown in the presence of 2 mM sodium butyrate was ten times as much as that of the control p-815-4 cells. Approximately 90% of the glycosaminoglycans isolated from the control cells and 70% from the butyrate-treated cells were found to be chondroitin 4-sulfate by enzymic digestion. The remainders were chondroitinase ABC-resistant. Hyaluronic acid and dermatan sulfate were not detected in either control cells or butyrate-treated cells. The chondroitinase ABC-resistant fraction of glycosaminoglycans from butyrate-treated cells showed a molar ratio of sulfate to uronic acid of more than 2.0, and provided some physicochemical properties characteristic to reference bovine lung heparin.

Animals↗