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Biomedical subjects

H Tsuruta

Publications and source records attributed to H Tsuruta.

At least 55 records · Page 3Linked to original sources
PubMed1998

Changes in expression of the antigen recognized by monoclonal antibody A7 in human pancreatic carcinoma cells following exposure to anticancer agents.

Techniques which can increase the expression level of tumor-associated antigens may improve immunotargeting therapy. We studied the reactivity of MAb A7 toward an antigen expressed on the surface of the human pancreatic cancer cell line HPC-YS after treatment with various antitumoral agents. When we applied 1 microg/ml mitomycin C (MMC) or 0.1 microg/ml neocarzinostatin (NCS) for 1 h, A7 recognizing antigen expression was enhanced until 24 h after the treatments. At a dose that completely suppressed cell growth, increased antigen expression was maintained for 96 h. Therefore, this study suggests that the combined application of an anticancer drug and MAb A7 may be useful for immunotargeting chemotherapy.

Antibiotics, Antineoplastic↗
PubMed1998

Novel quartz flow-cell as a post-column photochemical reactor for high-performance liquid chromatography.

The construction of a new post-column photochemical reactor with quartz flow cells in series for high-performance liquid chromatography (HPLC) is described. The performance of the new reactor was compared with a conventional open tubular PTFE coil reactor. The sensitivity, accuracy and precision obtained with both reactors are comparable. The new reactor has the obvious advantages of smaller cell volume as well as inertness and resistance to not only light and heat produced by the UV lamp, but also to organic solvents in the mobile phases, which results in greatly improved durability, reduced peak broadening and shorter chromatographic run times. Application of the new reactor to the fluorescence detection of DU-6859a, a new fluoroquinolone antimicrobial agent, in human serum is reported.

Anti-Infective Agents↗
PubMed1998

Targeted chemotherapy in mice with peritoneally disseminated gastric cancer using monoclonal antibody-drug conjugate.

The murine monoclonal antibody A7 (MAb A7) is reactive against most human gastric cancer cell lines. Using a nude mouse peritoneal dissemination model of human gastric cancer, we investigated targeted chemotherapy using a conjugate of neocarzinostatin (NCS) with MAb A7 (A7-NCS). After demonstrating cytotoxicity of the complex against the human gastric cancer cell line MKN45 in vitro, we intraperitoneally injected A7-NCS, NCS or saline into nude mice bearing peritoneally disseminated human gastric cancer. A7-NCS inhibited peritoneal dissemination significantly more effectively than NCS. MAb A7 may prove to be an effective carrier for antineoplastic drugs in patients with peritoneal dissemination of gastric cancer.

Animals↗
PubMed1998

Purification and some characteristics of phosphatase of a psychrophile.

The phosphatase of a psychrophile was purified by ammonium sulfate fractionation, and a sequence of chromatographies on DEAE-Cellulofine, butyl-Cellulofine, Sephacryl S-100, and Mono-Q columns. The purified enzyme preparation was found to be electrophoretically homogeneous on native- and SDS-PAGE, and its molecular mass was determined to be 38.4 kDa by MALDI-TOF mass spectrometry. Maximal activity was observed at 30 degrees C and pH 6.0. Furthermore, the activity of this enzyme at 0 and 5 degrees C was 27 and 28%, respectively, of that at 30 degrees C. The enzyme was stable in the pH range of 6.0 to 8.0 and up to 20 degrees C. The enzyme was affected by metal ions; the activity was enhanced by Mg2+ and Ca2+ ions, but depressed by Zn2+ ions. Analysis of the amino acid composition indicated that this phosphatase contains no S-S bond, and only a few prolyl residues necessary to retain the rigid structure of a protein molecule. The phosphatase shows typical features of a cold enzyme; high catalytic activity at low temperature and rapid inactivation at an intermediate temperature.

Animals↗
PubMed1998

LDL apheresis for arteriosclerosis obliterans with occluded bypass graft: change in prostacyclin and effect on ischemic symptoms.

To study the mechanism of efficacy of low-density lipoprotein (LDL) adsorption for arteriosclerosis obliterans (ASO), eight ASO patients without indication for bypass surgery underwent LDL apheresis twice a week for 5 weeks and the change in prostaglandin 12 (PGI2) and thromboxane A2 (TXA2) due to LDL apheresis was measured. The concentration of 6-keto-PGF1alpha, a metabolite of PGI2, in systemic venous blood significantly increased from 10.4 +/- 1.8 to 42.0 +/- 10.6 pg/mL (P<0.05) after one session of LDL apheresis, while no significant change of TXB2, a metabolite of TXA2, was encountered. The ratio of 6-keto-PGF1alpha/TXB2 also rose dramatically from 0.213 +/- 0.044 to 0.522 +/- 0.128 (P<0.05). In five patients, the ischemic clinical symptoms improved and both the concentration of 6-keto-PGF1alpha and the ratio of 6-keto-PGF1alpha/TXB2 increased significantly, whereas in three patients there was no effect on clinical symptoms and neither parameter changed. These results suggest that elevated production of PGI2 from vascular cells due to LDL apheresis might contribute to improvement of ischemic symptoms.

Aged↗
PubMed1998

Prevention of co-elution of steroid sulfates with serum proteins from pre-column in column-switching HPLC system.

A method to prevent co-elution of steroid sulfates with proteins in serum from the pre-column in column-switching HPLC was developed. The pre-column, a polymer-coated mixed function column, was used for ion-pair chromatography with 5 mM tetra-n-butylammonium (TBA) ion. As steroid sulfates, estriol 3-sulfate, dehydroepiandrosterone 3-sulfate and pregnenolone 3-sulfate were used. Human serum (25 microl) was diluted with mobile phases including 5, 100 and 500 mM TBA ion, and then injected directly into the pre-column. The peak areas of the steroid sulfates in serum samples were compared with those of the steroid standards without serum. When 25/microl of serum was diluted with mobile phase including 100 or 500 mM TBA ion, the steroid sulfates in serum were retained in the pre-column; however, the steroid sulfates from the same sample diluted with mobile phase containing 5 mM TBA ion were not retained in the pre-column. Addition of an excess amount of counter ion (TBA ion) into the serum sample made it possible to retain the steroid sulfates in the pre-column. This method was applied to column-switching HPLC for measurement of steroid sulfates in serum using a semi-microcolumn as the analytical column.

Blood Proteins↗
PubMed1998

[A case of cardiac rupture which occurred 34 years after mastectomy].

We experienced a case of cardiac rupture associated with mastectomy. A 78-year-old woman, who underwent left mastectomy 34 years before, complained of bleeding from a chest tumor located on the operative scar of the left mastectomy and postoperative irradiation. The tumor was noticed 10 months prior and became larger and repeated bleeding. It was first diagnosed as hemangioma by nearby practitioner. She was referred to the university hospital because of uncontrollable bleeding from the tumor. Without definite diagnosis, the tumor ruptured suddenly 52 days after the admission and the patient lapsed into the state of hemorrhagic shock and cardiopulmonary resuscitation was performed. Following emergency operation was performed on stand-by of cardiopulmonary bypass (CPB). The operation was successful with the aid of partial CPB and the final diagnosis of cardiac rupture was determined during the surgery. A case of cardiac rupture after mastectomy and radiation is rare, and this is the first report in the Japanese literature to date. The patient could be saved because the operation was performed on stand-by CPB.

Aged↗
PubMed1998

[Application of monoclonal antibody for drug delivery system--missile therapy for cancer].

Clinical applications of monoclonal antibody for selective delivery of anticancer drug, toxin and radioisotope were reviewed. The difficulties in preparation and clinical application of chemoimmunoconjugate were pointed out. Also the difficulties of immunotoxin in clinical trial due to its high toxicity had been discussed and it is assumed that development of blocked ricin may overcome many problems related to toxicities. Clinically most advanced immunoconjugate seems to be radioimmunoconjugate. Among three types of immunoconjugates preparation of radioimmunoconjugate is easiest and some promising clinical trials were introduced in this review.

Animals↗
PubMed1997

Reduced blood accumulation of biotinylated monoclonal antibody A7 after the subsequent administration of avidin.

Clear immunoscintigraphy with radiolabeled monoclonal antibodies (MAbs) requires a high tumor tissue/blood ratio of radioactivity. In this study, we attempted to obtain a high tumor tissue/blood ratio by the active removal of radiolabeled MAb from the circulation, using the avidin-biotin system. Biotinylated 125I-labeled MAb A7 was injected intravenously into nude mice bearing a human colon cancer (WiDr) xenograft. Avidin was injected 24 h later. The tumor tissue/blood ratio of radioactivity was almost four times that of controls. These results suggest that biotinylated 125I-labeled MAb A7 and avidin are potentially useful for the rapid immunodetection of human colon cancer.

Animals↗
PubMed1997

Decreased renal accumulation of biotinylated chimeric monoclonal antibody-neocarzinostatin conjugate after administration of avidin.

Murine monoclonal antibodies (mAbs) such as A7 administered to humans induce a human anti-mouse antibody response. Moreover, because Fab fragments of mAbs are able to penetrate target tumors easily, they may be more suitable than intact mAb to be carriers of anticancer agents such as neocarzinostatin (NCS), which are rapidly inactivated in the blood. To address these problems, chimeric A7 Fab fragment-NCS conjugate (chA7Fab-NCS) was produced. However, large amounts of 125I-labeled chA7Fab-NCS accumulate in the kidney and can lead to renal dysfunction. To decrease renal accumulation of chA7Fab-NCS, chA7Fab was biotinylated and administered with a subsequent injection of avidin. Human pancreatic carcinoma-bearing nude mice were injected with 125I-labeled biotinylated chA7Fab-NCS with or without subsequent administration of avidin. The accumulation of 125I-labeled biotinylated chA7Fab-NCS in tissue samples was measured at appropriate time intervals. 125I-labeled biotinylated chA7Fab-NCS was cleared more rapidly from the blood and the kidney with the administration of avidin than without it. There was no difference between tumor accumulation in these groups. The tumor/blood ratio of radioactivity of 125I-labeled biotinylated chA7Fab-NCS was significantly higher with subsequent administration of avidin than without avidin. The administration of biotinylated chA7Fab-NCS followed by avidin may enhance safety and permit the administration of larger doses of NCS without the subsequent development of renal failure. A larger amount of 125I-labeled biotinylated chA7Fab-NCS was retained in the liver and spleen with the subsequent administration of avidin than without avidin.

Adenocarcinoma↗
PubMed1997

The effects of nitroglycol on rat isolated cardiac muscles.

To elucidate the action of nitroglycol (Ng) on cardiac muscles, the contractile and chronotropic responses of the isolated rat cardiac muscles to Ng in a cumulative manner were investigated. Ng produced negative chronotropic and inotropic effects on spontaneously beating right atria in concentrations ranging from 10(-7) to 3 x 10(-4) M. Ng also produced dose-dependent negative inotropic effects on electrically driven left atrial muscles. On the other hand, in right ventricle muscles, Ng induced positive inotropic effects. These results suggest that Ng acts directly on the cardiac muscles as well as vascular smooth muscles in acute poisoning.

Analysis of Variance↗
PubMed1996

Effect of exposure to four organic solvents on hepatic cytochrome P450 isozymes in rat.

Changes of cytochrome P450 isozymes in livers of rats after exposure to four solvents at 4000 ppm for 6 h, were studied by enzyme assays and immunochemical detection using antibodies to cytochrome P450 isozymes. Toluene, benzene and trichloroethylene (TRI) exposure resulted in a significant increase in the activities of nitrosodimethylamine demethylase (152%, 134% and 118%) and 7-pentoxyresorufin O-depentylase (14-, 5- and 2.5-fold), respectively. 1,1,1-Trichloroethane (TCE) showed little effect on the activities of the enzymes. Anti-CYP2E1 and anti-CYP2B1/2 inhibitable activity of toluene side-chain oxidase was significantly enhanced in toluene-, benzene- and TRI-treated rats. Anti-CYP2C11 inhibitable activity was greatly reduced as compared with control. The change in CYP2E1 and CYP2C11 was confirmed by the increase and decrease in the activities inhibited by 4-methylpyrazole and cimetidine, respectively. Western blot analysis revealed that the increase in peak area of bands recognized by anti-CYP2E1 was consistent with toluene inhibition results. CYP2B1/2 was not detectable in control rats, but it was strongly induced by toluene, followed by benzene and TRI. Some increases in the peak areas of bands recognized by anti-CYP2A1 and CYP-4A1 were also observed in the three solvents exposed rat microsomes. Little immunoreactivity was found with anti-CYP1A1 in all microsomes, and no obvious change in peak area of bands recognized by anti-CYP3A and anti-CYP2C13 was observed. TCE exposure showed little effect on these bands. The formation of phenol and hydroquinone from benzene was enhanced to different degree by toluene, benzene and TRI. The hydroxylation of testosterone at 6 beta and 7 alpha was increased by benzene, and benzene and TRI, respectively. However, the metabolism at 16 alpha and 2 alpha was profoundly suppressed by the solvents except TCE. These results showed that the four solvents have different effects on specific cytochrome P450 isozymes and on the metabolism of both endogenous and exogenous substances.

Animals↗
PubMed1996

Applicability of monoclonal antibody Fab fragments as a carrier of neocarzinostatin in targeting chemotherapy.

Two types of fragments of MAb A7 were produced to improve the efficacy and safety in targeting chemotherapy with neocarzinostatin. In this study, 125I-labeled F(ab')2 and Fab fragments of MAb A7 and 125I-labeled MAb A7 were injected intravenously into mice with pancreatic carcinoma xenografts, and the accumulation of each antibody in the tumors was compared. A greater amount of the 125I-labeled Fab fragments of MAb A7 localized in the tumor 2 h following the injection than was observed with the other probes. Relatively less 125I-labeled MAb A7 localized in the tumor 2 h following the injection than was observed with the other two probes. Moreover, reaction of rabbit antimouse IgC with the Fc portion, which is the most immunopotent region of the Fab and F(ab')2 fragments of MAb A7 and MAb A7, was determined by ELISA; the weakest reaction was observed with the Fab fragments of MAb A7. These results suggest that the Fab fragments of MAb A7 may be more suitable carriers of an anticancer drug that is inactivated rapidly in the blood, such as NCS, in targeting chemotherapy than either intact MAb A7 or the F(ab')2 fragments of MAb A7.

Animals↗
PubMed1996

Effects of neocarzinostatin-chimeric Fab conjugates on the growth of human pancreatic carcinoma xenografts.

Neocarzinostatin (NCS) was bound covalently to human/mouse chimeric Fab fragments of MAb A7 (chA7Fab) directed against human pancreatic carcinoma. The anti-tumour effect of chA7Fab-NCS was tested in a nude mouse model on pancreatic carcinoma and compared with A7-NCS or NCS alone. The anti-tumour effect of chA7Fab-NCS increased in a dose-dependent manner and was significantly greater than either A7-NCS or NCS. Tumour growth was completely suppressed after the administration of chA7Fab-NCS. An enzyme-linked immunosorbent assay with rabbit anti-mouse immunoglobulin was performed to examine the antigenicity of chA7Fab. ChA7Fab had less reactivity with rabbit anti-mouse immunoglobulin than either whole antibody A7 or murine Fab fragments of A7. Thus, chA7Fab-NCS can inhibit human pancreatic cancer growth in an animal and may be useful for targeting chemotherapy to pancreatic cancer in humans.

Animals↗
PubMed1996

Distribution of neocarzinostatin conjugated to biotinylated chimeric monoclonal antibody Fab fragments after administration of avidin.

We have developed chimeric Fab fragments of MAb A7 (chA7Fab) and have reported on their potential usefulness as a carrier of neocarzinostatin (NCS). However, a large amount of chA7Fab accumulates in the kidneys which might cause renal failure. This was one of the major side-effects of the chA7Fab-NCS immunoconjugate administered to humans. To decrease the kidney accumulation of chA7Fab, chA7Fab was biotinylated and administered with a subsequent injection of avidin to nude mice with pancreatic cancer. The accumulation of biotinylated chA7Fab in the blood and the kidneys decreased significantly after the injection of avidin. In a separate experiment with biotinylated chA7Fab-NCS, the blood and kidney accumulation decreased significantly after the injection of avidin. These findings suggest that the injection of biotinylated chA7Fab complexed with NCS followed by avidin may be safer and may permit the administration of larger doses of NCS without the subsequent development of renal failure.

Animals↗
PubMed1996

Characterization of steroid/cyclodextrin inclusion compounds by x-ray powder diffractometry and thermal analysis.

Two inclusion compounds, progesterone with beta- and gamma-cyclodextrin, were studied with X-ray powder diffractometry and thermal analysis. Disappearance of characteristic X-ray diffraction patterns of the two compounds as well as the appearance of a new diffraction pattern for each were found when formation of the inclusion compounds was completed. The X-ray diffraction patterns of beta-cyclodextrin measured at various temperatures showed a structural change occurring between 60 degrees C to 80 degrees C, which coincided well with the DSC endothermic peak around 75 degrees C. Results suggest that changes in the X-ray diffraction patterns of cyclodextrin during inclusion formation and during heating is due to the displacement of adsorbed water by progesterone in the cavity of cyclodextrin.

Crystallography, X-Ray↗