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K Tsujikawa

Publications and source records attributed to K Tsujikawa.

At least 55 records · Page 3Linked to original sources
PubMed1994

Serum hepatocyte growth factor activity and hepatocyte proliferation in Long-Evans with a cinnamon-like coat color rats with hepatic lesions.

We classified hepatic lesions spontaneously developed by Long-Evans with a cinnamon-like coat color (LEC) rats into the following four stages: Normal liver, acute hepatitis, chronic hepatitis, and hepatoma, by biochemical tests of the sera, and anatomical and histopathological examination of the livers. Hepatocyte growth factor (HGF) activity in the sera of LEC rats which developed acute hepatitis, chronic hepatitis, and hepatoma was higher than that of normal LEC rats. In particular, HGF activity in the sera of the LEC rats with acute hepatitis was about 70-fold that of normal LEC rats. However, primary cultured hepatocytes of LEC rats with hepatic lesions were hardly proliferated by stimulation with EGF and insulin in vitro or with increased HGF in vivo. These results suggest that the hepatocytes of LEC rats with hepatic lesions disorder the signal transduction of growth factors.

Acute Disease↗
PubMed1994

Abnormal accumulation of copper-metallothionein in the liver and kidney of Long-Evans rats with a cinnamon-like coat color (LEC rats).

We determined the copper (Cu) and metallothionein (MT) concentrations in the liver and kidney supernatants of Long-Evans rats with a cinnamon-like coat color (LEC rats), and also measured the Cu and MT levels in the serum of these rats. Seven-week-old rats had abnormally high levels of both substances in the liver. The levels in the liver supernatant were over 80- and 16-fold higher, respectively, in LEC rats than in normal 7-week-old Wistar rats. LEC rats suffering from acute hepatitis or hepatoma had a much higher level of hepatic MT, but the Cu level was higher only in the liver of those with hepatoma. The serum levels of Cu and MT in LEC rats with acute hepatitis were more than 10-fold higher than those in normal LEC rats. These levels were decreased in the rats with chronic hepatitis or hepatoma. In the liver of LEC rats with hepatoma, the area of hepatocellular carcinoma and of noncancerous liver showed over twice higher Cu and MT levels than the area of cholangiofibrosis. The Sephadex G-75 elution profile from the liver supernatant of a normal LEC rat showed that the peak of Cu closely corresponded to that of MT recognized with anti-MT antiserum. The levels of Cu and MT in the kidney supernatant of LEC rats with acute hepatitis were more than 25-fold higher than in that of normal LEC rats. However, there were no marked increases in the levels in the kidney supernatant of LEC rats with chronic hepatitis or hepatoma.

Animals↗
PubMed1994

Studies on pharmacological activation of human immunoglobulin G by chemical modification and active subfragments. XIII. Effect of carboxamidemethylated Fc fragment (CM-Fc) on type II collagen-induced arthritis in DBA/1J mice.

The effect of carboxamidemethylated Fc fragment (CM-Fc) from human immunoglobulin G (IgG) on type II collagen (C II)-induced arthritis (CIA) in DBA/1J mice was studied. CM-Fc suppressed the development of CIA while Fc fragment did not. CM-Fc inhibited the increase in serum anti-C II IgG. CM-Fc suppressed C II-induced delayed type hypersensitivity (DTH) in DBA/1J mice. Moreover, the C II-induced proliferation of splenocytes from mice immunized with C II was suppressed by the administration of CM-Fc. Following an analysis of the lymphocyte population, a decreased percentage of B220+ cells and ratio of L3T4+/Ly-2+ cells was observed in lymph nodes of CM-Fc administered mice as compared with those of control group. These results suggest that CM-Fc inhibits CIA by regulating lymphocyte function.

Animals↗
PubMed1994

Induction and subcellular localization of metallothionein in regenerating rat liver.

A highly specific antiserum against rat liver metallothionein (MT) was raised in a Japanese white rabbit. Using this anti-MT antiserum, we found that MT was localized in the nuclei as well as in the cytoplasm of hepatocytes in newborn rats. Since it is known that these cells are growing actively, we suspected that there was a relationship between the localization of MT in cell nuclei and the cell proliferation. Therefore, the induction and subcellular localization of MT were examined in rat liver remaining after 70% removal. MT was induced in the remnant liver rapidly after the hepatectomy, its concentration being about 80-fold higher than that of the intact liver. Flow cytometric analysis revealed that MT was translocated into the nuclei from the cytoplasm of hepatocytes during liver regeneration after partial hepatectomy. The highest MT level in the nuclei was observed 24 h after hepatectomy. MT-stained positive nuclei were in S to G2M phases of the cell cycle of regenerating hepatocytes, and the nuclei in G1 phase were not stained with anti-MT antiserum. The increase in hepatic MT levels did not directly cause MT translocation into the nuclei. These results suggested that MT was a cell cycle-dependent, nuclear protein.

Animals↗
PubMed1993

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. IX. Anti-inflammatory activity of completely alkylated heavy chain (C.Fr.I-H).

The anti-inflammatory activity of completely reduced and carboxamide-methylated heavy chain of all disulfide bonds in human serum immunoglobulin G (IgG) (C.Fr.I-H) was investigated using some experimental inflammatory models. C.Fr.I-H significantly inhibited carrageenin-induced paw edema and pleurisy, and serotonin-induced paw edema. The carboxamide-methylated heavy chain of interchain disulfide bonds in IgG (Fr.I-H) exhibited similar inhibitory activities to C.Fr.I-H on carrageenin-induced paw edema and pleurisy, while it was ineffective on serotonin-induced paw edema. These results suggest that complete alkylation of disulfide bonds in a heavy chain caused stronger anti-inflammatory activities than partial alkylation.

Alkylation↗
PubMed1993

Studies on pharmacological activation of human immunoglobulin G by chemical modification and active subfragments. X. Effect of carboxamidemethylated Fc fragment (CM-Fc) from human immunoglobulin G on delayed type hypersensitivity.

The anti-allergic activity of the carboxyamidemethylated Fc fragment (CM-Fc) from human serum immunoglobulin G (IgG) was studied using sheep red blood cell-induced delayed type hypersensitivity in mice (SRBC-DTH). CM-Fc suppressed the DTH response when administered 30 min before, or 4 h after the SRBC challenge, but not when administered 8 h or more after the challenge. The Fc fragment showed no activity. CM-Fc administration 30 min before the challenge was unable to suppress the DTH response in the cyclophosphamide (CY)-treated mice. However, adoptive transfer of splenocytes from mice treated with CM-Fc to CY-pretreated mice caused suppression of the SRBC-DTH response. These results suggest that CM-Fc suppressed the DTH response by mediating the function of CY-susceptible cells.

Animals↗
PubMed1993

Studies on thermophile products. VI. Activation of mouse peritoneal macrophages by bis(2-hydroxyethyl) trisulfide.

The biological effects of a cytotoxic substance (BS-1), isolated from Bacillus stearothermophilus UK563 and identified as bis(2-hydroxyethyl) trisulfide, on elicited mouse peritoneal macrophages induced by a casein injection, were investigated in vitro. BALB/c mouse macrophages treated or pretreated with BS-1 (1-10 micrograms/ml) showed cytotoxicity against syngeneic DBA/2 mouse P815 mastocytoma. BS-1 also showed weak cytotoxicity directly against P815 in the absence of macrophages. BS-1 significantly increased the glucose consumption of macrophages without producing cytotoxicity. This trisulfide compound increased nitric oxide formation, interleukin-1 production and prostaglandin E2 release in macrophages. It did not, however, increase the production of active oxygen species in macrophages, but it reduced cytochrome c in the presence of phagocytes. These results indicate that BS-1 activates macrophages to the cytolytic stage.

Animals↗
PubMed1992

Inhibitory effects of bis(2-aminohexyl)disulfide and its analogues on polymorphonuclear leukocyte functions in vitro.

Water soluble analogues of the anti-inflammatory compound, bis(2-aminopropyl)disulfide dihydrochloride (compd. I) with a butyl (II), phenyl (III), benzyl (IV) or pyrrolidinyl group (V) instead of the methyl group were synthesized, and their effects on the functions of cells related to inflammation were studied in vitro. Compounds II, III and IV showed much higher inhibitory activity than compd. I on formyl Met-Leu-Phe (FMLP)-induced O2(-)-generation of polymorphonuclear leukocytes (PMNs) and platelet aggregation. Compound II showed the strongest activity among the compounds (IC50 values: 2.6 microM). The inhibition of O2(-)-generation of PMNs by compd. II was the most effective when FMLP was used as a stimulant rather than when phorbol myristate acetate, A-23187 and opsonized zymosan were used. However, compd. II was not an O2(-)-scavenger. Compounds II, III and IV significantly inhibited a series of activation processes in PMNs, chemotaxis, phagocytosis and lysosomal enzyme release at doses ranging from 10 to 100 microM. Under these doses, compds II, III and IV did not affect the histamine release from mast cells or the hemolysis of erythrocytes. These results strongly suggest that the anti-inflammatory action caused by compd. II and its analogues was at least partly due to inhibition of several functions of PMNs and platelets.

Amines↗
PubMed1992

Preparation of biologically active and site specifically radioiodinated recombinant human insulin-like growth factor-I.

Recombinant human insulin-like growth factor-I (rhIGF-I) was iodinated using a lactoperoxidase-catalyzed labeling method. The labeled products were separated into more than five fractions by ion-paired reverse-phase high performance liquid chromatography (HPLC). A fraction (peak 1), which showed the highest yield and radioactivity, was found to be biologically active in the BALB/c 3T3 cell proliferating system. The site of the iodination was investigated by S-pyridylethylation followed by trypsinization and separation with HPLC using reverse phase columns. From the amino acid analysis of the peaks which were radioactive, the iodination site of peak 1 was revealed to be Tyr-24 and Tyr-60. This is the first report of the biological activity of radioactive peptide hormone with a defined labeled site.

3T3 Cells↗
PubMed1991

Localization of metallothionein in nuclei of growing primary cultured adult rat hepatocytes.

In primary cultured adult rat hepatocytes stimulated by epidermal growth factor and insulin, dramatic changes in the subcellular distribution of metallothionein were clarified by indirect immunofluorescence using antisera specific for this protein. Metallothionein was detected only in the cytoplasm of cultured hepatocytes in the G0 and G1 phases, but was concentrated in the cell nuclei in the early S phase. The strongest staining pattern in the nuclei was observed 12 h after stimulation. Subsequently, the intensity of metallothionein staining in the nuclei decreased. These results suggest that primary cultured hepatocytes are suitable for examining the relation between subcellular localization of metallothionein and cell growth.

Animals↗
PubMed1991

Effects of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide on various ulcer models in rats.

The effects of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide (compd. III-1a) on various experimental ulcers were investigated. The oral administration of compd. III-1a at doses ranging from 30 to 300 mg/kg inhibited the acute gastric ulcerations induced by ethanol, HCl.aspirin and indomethacin in rats. Compound III-1a significantly inhibited the water immersion stress-induced gastric ulcer at doses of 3 mg/kg, p.o. The anti-ulcer activity of plaunotol as a reference drug was equivalent on an ethanol-induced ulcer to that of compd. III-1a, but weaker on HCl.aspirin, indomethacin and stress-induced ulcers than that of compd. III-1a. On indomethacin-produced gastric antral ulcer, compd. III-1a showed the same significant inhibitory activity as spizofurone did at a dose of 100 mg/kg, p.o. Compound III-1a also inhibited hemorrhagic shock-, diethyldithiocarbamic acid (DDC)-and platelet activating factor (PAF)-induced ulcers dose-dependently. Plaunotol only showed significant inhibitory activity on PAF-induced ulcer in these three ucler models. The consecutive administration of compd. III-1a (100 mg/kg, p.o.) twice a day significantly accelerated the healing of an acetic acid-induced ulcer and that of plaunotol (200 mg/kg, p.o.) showed the same activity. Moreover, orally administered compd. III-1a at a dose of 100 mg/kg decreased the gastric acid secretion in pylorus-ligated rats. The results in the present study suggest that compd. III-1a has the dual action on ulcer formation.

Animals↗
PubMed1991

Further studies on the anti-ulcerogenic effects of compound, 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide.

Tha anti-ulcerogenic mechanism of 2-(E-2-decenoylamino)ethyl 2-(cyclohexylethyl) sulfide (compd. III-1a) was investigated in various gastric defensive factors. Compound III-1a maintained the high molecular glycoprotein (relative content of Fr. I hexose) and accelerated hexosamine synthesis which were reduced by water immersion stress. But plaunotol did not have these actions. The lipid peroxide level in the gastric mucosa from water immersion stressed rat was lowered by the administration of compd. III-1a. Compound III-1a maintained prostaglandin E2 (PGE2) and PGI2 contents which were reduced in the early phase of the stress and accelerated PGs synthesis in the late phase of the stress. Furthermore, compd. III-1a maintained phospholipase A2 (PLA2) activity which was reduced by the stress. The plaunotol treated group showed the same tendency as the compd. III-1a treated group on the lipid peroxide level, PGE2 and PGI2 contents, and PLA2 activity, but the potency of plaunotol was less than that of compd. III-1a. Compound III-1a accelerated gastric cell proliferation in pyloric glands of hydrocortisone treated rats. Tetragastrin accelerated significantly the cell proliferation in fundic glands. The sucralfate treated group showed the same tendency as the compd. III-1a treated group but the potency of sucralfate was less than that of compd. III-1a. The results in the present study suggest that compd. III-1a has a protective action on gastric mucosa.

Animals↗
PubMed1991

Isolation of a new antitumor substance from Bacillus stearothermophilus.

A new antitumor substance, BS-1, was isolated from the autolysate and culture filtrate of Bacillus stearothermophilus UK563 by ethylacetate extraction and HPLC. BS-1 inhibited the proliferation of mouse macrophage-like cells, P388-D1 (IC50: 4 micrograms/ml) and mouse mastocytoma, P-815 (IC50: 0.6 microgram/ml), but not that of Balb/c 3T3.

Animals↗
PubMed1989

Studies on pharmacological activation of human serum immunoglobulin G by chemical modification and active subfragments. VIII. Effect of carboxamide-methylated light chain (Fr.I-L) on leukocyte functions.

Human serum immunoglobulin G light chain (Fr.I-L), which was reduced and carboxamide-methylated, showed no effect on formyl-methionyl-leucyl-phenylalanine (FMLP)-induced chemotaxis nor on phagocytosis of yeasts when directly added to guinea pig polymorphonuclear leukocytes (PMNs). However, intravenously administered Fr.I-L inhibited emigration of leukocytes into the peritoneal cavity and promoted phagocytosis of yeasts in a yeast-induced peritonitis model in mice. Moreover, Fr.I-L reduced FMLP-induced chemiluminescence (CL) from PMNs. These facts indicated that the anti-inflammatory action of Fr.I-L was caused by inhibiting emigration of leukocytes into the injured site and scavenging superoxide radicals from the cells.

Animals↗
PubMed1989

Enhancement of heparin-binding ability of fibronectin by S-carboxamide-methylation.

Human plasma fibronectin (FN) was reduced and carboxamidemethylated, and its binding ability to several matrices was analyzed in vitro. The binding of S-carboxamidemethyl (Cam)-FN to heparin-Sepharose was not influenced by either 4 M urea, 0.5 M NaCl or 0.5% heparin, but was disrupted by the coexistence of urea and NaCl or heparin. S-Cam-FN, compared with intact FN, obviously had a more potent ability to bind heparin, while it had little or no binding ability to gelatin, fibrin and thrombin-stimulated platelets. A conformational change of S-Cam-FN by heparin-binding has been proposed as a possible mechanism from the result of circular dichroic spectrum measurement.

Binding Sites↗
PubMed1989

Further studies on the pharmacological effect of the anti-inflammatory compound, bis[2-(E-2-octenoylamino)ethyl] disulfide.

Further studies on the pharmacological effect of orally administered bis[2-(E-2-octenoyl-amino)ethyl] disulfide (compd. I-3) was examined by using several experimental models in vivo. Compound I-3 showed analgesic activity, inhibiting both acetic acid- and acetylcholine-induced writhings in mice. This compound also showed antipyretic activity against yeast-induced fever in rats, and significantly inhibited arachidonic acid-induced mortality in mice. However, it had no effect on serotonin-induced paw edema formation or platelet activating factor-acether-induced mortality in mice. The effects of compd. I-3 are suggested to be due to inhibition of prostaglandin biosynthesis.

Amides↗
PubMed1989

The effect of a cystamine derivative, bis[2-(E-2-hexenoylamino)ethyl] disulfide, on rat platelet aggregation.

Bis[2-(E-2-alkenoylamino)ethyl] disulfides (compds. I), synthesized from cystamine and 2-trans fatty acids, inhibited collagen-induced rat and rabbit platelet aggregation. The most potent compound was bis[2-(E-2-hexenoylamino)ethyl] disulfide (compd. I-1), and this compound suppressed thromboxane B2 formation from arachidonic acid in rat platelets. The results suggested that compd. I-1 has an inhibitory effect on cyclooxygenase.

Alkenes↗