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Biomedical subjects

M Kinuta

Publications and source records attributed to M Kinuta.

At least 37 records · Page 2Linked to original sources
PubMed1995

[A comparison of intra-arterial chemoembolization and infusion chemotherapy for liver metastases of breast cancer].

Seventeen patients with liver metastases of breast cancer were treated with a combination of intra-arterial chemotherapy and endocrine therapy at our hospital from 1986 to 1994. Of 17 patients, 9 were treated with transarterial chemoembolization through hepatic artery using 40-50 mg/body of 4'epi-adriamycin (epi-ADM) and lipiodol, and the other 8 were treated with hepatic infusion chemotherapy using 20-30 mg/body of epi-ADM every 2 weeks. All patients were followed by endocrine therapy with oral administration of 800-1,200 mg/day of medroxyprogesterone acetate (MPA). The results were as follows: 1) The comparison of response rate between the two groups was not substantially changed (44.4% x 4/9 in TAE group and 50.0% x 4/8 in Reservoir group). 2) Duration of response was 4-45 months (mean 25 months) in TAE group and 3-15+ alpha months (mean 8.7 months) in Reservoir group. But in the latter group, 3 patients are now under treatment. 3) At one year, the survival rates were 44.4 percent in TAE group and 50.0 percent in Reservoir group. We conclude that combination of intra-arterial chemotherapy and endocrine therapy is a useful treatment modality for controlling liver metastases of breast cancer.

Adult↗
PubMed1994

High-performance liquid chromatographic determination of taurine and hypotaurine using 3,5-dinitrobenzoyl chloride as derivatizing reagent.

A method for the determination of taurine and hypotaurine in biological samples involving the preparation of their 3,5-dinitrobenzoyl derivatives followed by HPLC was established. Taurine and hypotaurine in aqueous media were reacted with 3,5-dinitrobenzoyl chloride in the presence of triethylamine to prepare 3,5-dinitrobenzoyl derivatives. These derivatives were separated on a C18 reversed-phase column and detected by recording the absorbance at 254 nm. Derivatives of taurine and hypotaurine were obtained in yields of 91.4 +/- 3.3 and 85.6 +/- 2.6%, respectively. The calibration graphs for taurine and hypotaurine were linear between 2.5 and 500 microM with correlation coefficients of 0.999. The method was applied to the determination of taurine and hypotaurine in human and rat urine and blood and in rat liver and heart.

Animals↗
PubMed1994

Isolation of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiolactic acid, a new metabolite of histidine, from normal human urine and its formation from S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine.

S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiolactic acid (CIE-TL), a novel imidazole compound with a sulphur-containing side chain, was isolated from normal human urine by ion-exchange column chromatography, and characterized by physicochemical analyses involving m.s., i.r. spectrophotometry, high-voltage paper electrophoresis and elemental analysis as well as chemical synthesis. CIE-TL was synthesized by the reaction of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (CIE-Cys) with NaNO2 in HCl. CIE-TL was also formed during enzymic degradation of CIE-Cys by rat liver or kidney homogenate in a phosphate buffer, possibly via the metabolic intermediate S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]-3-thiopyruvic acid, and this was accompanied by the formation of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid, a compound previously found in human urine [Kinuta, Yao, Masuoka, Ohta, Teraoka and Ubuka (1991) Biochem. J. 275, 617-621]. These results suggest that CIE-Cys [Kinuta, Ubuka, Yao, Futani, Fujiwara and Kurozumi (1992) Biochem. J. 283, 39-40] is a physiological precursor of the urinary compounds and that L-histidine is metabolized in part via an alternative pathway initiated by the adduction of natural thiol compounds such as cysteine and GSH to urocanic acid, the first catabolite of histidine.

Animals↗
PubMed1994

Follow-up study of combination treatment (TAE and PEIT) for unresectable hepatocellular carcinoma.

The subjects were 35 patients with unresectable hepatocellular carcinoma. The patients were divided into a transcatheter arterial embolization group (TAE group, 18 cases) and a combination therapy group receiving both TAE and percutaneous ethanol injection therapy (TAE+PEIT group, 17 cases). The 50% survival period was 21.1 months for the TAE group and 37.8 months for the TAE+PEIT group (P < 0.05). The longest survival period in the TAE group was 89 months. In the TAE+PEIT group, one patient has survived for 59 months. The actuarial 1-, 2-, and 3-year survival rates for the TAE group were 82%, 45%, and 22%, respectively. For the TAE+PEIT group the rates were 83%, 64%, and 64%, respectively. The TAE+PEIT group showed a significantly higher survival rate in the 895- to 1,074-day period as compared with the TAE group (P < 0.05). Overall, the survival rate tended to be higher in the TAE-PEIT group (P < 0.1). The therapeutic responses of tumors were measured by the maximal reduction rate within 6 months of TAE and PEIT. In the TAE group, a PR was seen in only four cases. In the TAE+PEIT group, CRs and PRs were achieved significantly more frequently than in the TAE group. When the patients were divided into a responder group (CR, PR, and MR) and a nonresponder group (NC and PD), survival was significantly longer in the responder group. The findings of the present study suggest that the combination therapy was useful for improving the survival of patients with unresectable hepatocellular carcinoma.

Adult↗
PubMed1994

[Early detection of non-palpable (T0) breast cancer: the diagnostic procedure for pathological discharge from the nipple].

Detection of non-palpable (T0) breast cancer by pathological nipple discharge is possible 3 years or more earlier than tumorous breast cancer. However, the definite diagnosis of T0 breast cancer has been considered to be very difficult because the standard diagnostic method such as exfoliative cytology and ductography were not totally reliable. In 1985 we first demonstrated the significance of CEA measurement in nipple discharge for diagnosis of T0 breast cancer. Since then CEA activity in nipple discharge was estimated in 60 patients with breast diseases by means of enzyme immunoassay using monoclonal anti CEA antibody. They include 17 with T0 breast cancer, 9 with borderline lesion, 20 with intraductal papilloma and 14 with fibrocystic diseases. When the cut off value of CEA concentration was set at 600 ng/ml, the sensitivity, specificity and accuracy were 76.5%, 100% and 92.2%, respectively. These levels were higher than those for mammography or cytology. In the past 7 years, 13 cases of T0 breast cancer were detected in our hospital. They accounted for 2.5% of total breast cancer cases. In conclusion, CEA measurement in nipple discharge is a useful method for the diagnosis of non-palpable breast cancer.

Biomarkers, Tumor↗
PubMed1993

Preparation and characterization of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione and its derivatives as proposed precursors of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine, a compound found in human urine.

Formation of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid (I) and S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (II), compounds found in human urine, has been demonstrated by enzymatic degradation of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (III). Compound (III) was chemically synthesized in 72% yield by incubating the reaction mixture of trans-urocanic acid and 3-fold excess GSH at 65 degrees C for 1 wk, which was accompanied by formation of N-(S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteinyl)glycine (IV) in 15% yield. S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]-N-gamma-glutamylcysteine (V) was produced by partial hydrolysis of compound (III) in HCl. The synthesized compounds were characterized mainly by fast-atom bombardment mass spectrometry and high-voltage paper electrophoresis as well as chemical degradation. Incubation of compound (III) with rat kidney homogenate in a Tris buffer (pH 8), formed compound (II) in 80% yield possibly via compound (IV). Yield of compound (II) was increased by adding glycylglycine to the reaction mixture. However, little degradation of compound (III) occurred in the use of rat liver, brain, heart or spleen homogenate as the enzyme source. Compound (II) was further metabolized to compound (I) by incubation with rat kidney homogenate in a phosphate buffer of pH 7.4. From these results, we suggest that the urinary compounds are products of enzymatic degradation of compound (III) and that GSH may participate in the metabolism of urocanic acid, the first catabolite of L-histidine.

Animals↗
PubMed1993

[Studies on combination therapy with TAE and percutaneous ethanol injection therapy for unresectable hepatocellular carcinoma].

We studied and analysed the effects of combination therapy with TAE and PEIT for unresectable HCC. The subjects were 28 patients (21 males, 7 females) with 31 tumors treated in the Department of Surgery, Osaka Teishin Hospital. The patients were divided into four groups on the basis of the tumor size (< 3 cm, 3-5 cm, 5-8 cm, > 8 cm). The therapeutic effect on the tumors was evaluated on the basis of the maximum reduction rate within 3 months after TAE and PEIT. The response rates after treatment were 87.5%, 60.0%, 25.0% and 0% for < 3 cm, 3-5 cm, 5-8 cm, and > 8 cm tumor size, respectively. The 50% survival period was 50.9 months. The 1-, 2-, 3- and 5-year survival rates were 92%, 76%, 52% and 32%, respectively. In the cases of over 8 cm, this combination therapy had no effects on the survival period. The findings of the present study suggest that the combination therapy was useful for the unresectable HCC of under 5 cm in diameter.

Carcinoma, Hepatocellular↗
PubMed1992

Assay of sialidase activity using ion-exchange chromatography and acidic ninhydrin reaction.

A new assay method for sialidase (EC 3.2.1.18) activity using ion-exchange chromatography and acidic ninhydrin reaction has been developed. Fetuin, 4-methylumbelliferyl-N-acetylneuraminic acid (MUB-NANA), gangliosides and N-acetylneuramin-lactose were examined as substrates. Free sialic acid liberated from these substrates by sialidase reaction was isolated with a Dowex 1-X8 column (trifluoroacetate form, 1.5 cm x 0.5 cm I.D.) and determined by acidic ninhydrin reaction. Among the substrates tested, MUB-NANA was the best in the present method, N-Acetylneuramin-lactose could not be used as the substrate, because it was not separated from liberated sialic acid under the conditions used. The recovery of N-acetylneuraminic acid was above 88%, and the sensitivity of the method was 20 nmol in 300 microliters of the reaction mixture. The method was applied to the sialidase assay during its purification from rat skeletal muscle, and a Michaelis constant of 1.15 mM was obtained with MUB-NANA as the substrate. The method using the acidic ninhydrin reaction was simple and exhibited good reproducibility.

Animals↗
PubMed1992

Isolation of S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine from human urine.

S-[2-Carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (I), a proposed precursor of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid [Kinuta, Yao, Masuoka, Ohta, Teraoka & Ubuka (1991) Biochem. J. 275, 617-721], was isolated from healthy human urine by using ion-exchange column chromatography. Identification of the isolated compound with compound (I) was performed by physicochemical analyses involving i.r., m.s. and n.m.r. spectrometries as well as high-voltage paper electrophoresis, t.l.c. and paper chromatography. Compound (I) was synthesized in 80% yield by incubation of a reaction mixture containing trans-urocanic acid and 3-fold excess of cysteine at 70-75 degrees C. From these results we suggest that natural thiol compounds such as cysteine and GSH participate in the metabolism of urocanic acid, a key metabolite of L-histidine.

Chromatography, Ion Exchange↗
PubMed1992

Efficacy of combination treatment--(TAE with adriamycin and ethanol)--for hepatocellular carcinoma.

Among 44 patients with hepatocellular carcinoma (HCC), combination treatment with both transhepatic arterial embolization (TAE) and ethanol injection therapy (EIT) was performed in 10 patients. Only two had tumors measuring less than 3 cm in diameter. In all, eight patients had solitary tumors and two had multiple tumors. The tumor was classified as stage I in one patient, stage II in six subjects, stage III in two patients, and stage IV in one subject prior to TAE, but one stage II case was changed to stage III after laparotomy. The clinical stage was I in two patients, II in six subjects and III in two patients. Five patients with tumors of stages I and II achieved either a complete response (CR) or partial response (PR). However, three patients with tumors of stages III and IV showed progressive disease (PD). Thus, the response rate (CR+PR) was 50%. For tumor stages I and II, the 1-, 2-, and 3-year survival values were 100%, 100%, and 83%, respectively. For tumor stages III and IV, the 1- and 2-year survival values were 75% and 25%, respectively. Combination treatment of HCC appears to be efficacious for tumor stages I and II.

Adult↗
PubMed1992

Programmed cell death in whole body and organ systems by low dose radiation.

New whole-body and organ systems were established to detect interphase cell death in the thymus, spleen and epithelial cells of intestinal crypts by low-dose radiation. Frozen sections of the thymus, spleen and intestine as thick as 8 microns were made after X-irradiation of whole body or removed organs, and then sections were stained with 0.02% erythrosin B solution. In unirradiated controls, a few numbers of erythrosin B positive cells (dead or dying cells) were observed in the thymus, spleen and intestinal crypt as a single cell death. When X rays were given to various strains of mice as a whole body dose, clusters of erythrosin B positive cells were produced. They appear at 2 hr after irradiation and reached maximum at 4 hr, remaining at a similar level until 8 hr after irradiation. The number of erythrosin B positive cells decreased after then by the elimination of dead cells, and they were observed like a single cell death at 24 hr after irradiation. When erythrosin B positive cells were scored 4 hr after irradiation, their total number and the number of cluster increased with increasing doses of X rays in the dose range from 0.05 to 0.5 Gy. It is noted that there were large differences in the radiation susceptibility among the inbred strains of mice for the induction of interphase cell death of thymic lymphocytes: e.g., high susceptibility in C57BL/6J and AKR/J, intermediate in N4, A/J, PT and ST, low in C3H/HeJ, HT, 101/H and DBA/2J, indicating that interphase cell death is genetically programmed. Similar results were observed with some chemical mutagens. Although a large increase of erythrosin B positive cells was observed in the thymus and spleen with methylprednisolone, there was no increase in the intestinal crypt, and vice versa with bleomycin, suggesting the organ specificity for the induction of interphase cell death by chemicals. For the in vitro method, the removed thymus was irradiated on the agar plate, and then incubated on the agar plate which was placed on the grid in the medium, so that the medium comes up to the organ through the agar plate. Frozen sections were made and stained with erythrosin B solution in the same way as the in vivo method. The number of erythrosin B positive cells in the organ culture system reached maximum at 5 hr after X-irradiation, e.g. slightly later than in the whole-body system. The efficiency was about 60% in C57BL/6J mice when compared with whole-body system.

Animals↗
PubMed1991

Isolation and characterization of 3-[(carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid from human urine and preparation of its proposed precursor, S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine.

3-[(Carboxymethyl)thio]-3-(1H-imidazol-4-yl)propanoic acid (I) was isolated from healthy human urine by using ion-exchange column chromatography, and characterized by physicochemical analyses involving i.r., m.s. and n.m.r. spectrometries as well as chemical synthesis. The urinary content was 0.04-0.07 mumol/l. Compound (I) was synthesized by the addition of mercaptoacetic acid to urocanic acid. In order to establish the origin of the compound. S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]cysteine (II) and S-[2-carboxy-1-(1H-imidazol-4-yl)ethyl]glutathione (III) were produced by similar reactions of urocanic acid with cysteine and GSH respectively. The yield of compound (II) was markedly increased by sunlight irradiation of the reaction mixture or by the use of cis-urocanic acid rather than the trans isomer. Incubation of compound (II) with rat liver homogenate in a phosphate buffer, pH 7.40, formed a major and some minor products of enzymic degradation, one of which was identified with compound (I). Exposure of rats to the sunlight for 2 days resulted in increase of the epidermal content of trans-urocanic acid from the normal value of 0.38 to 1.70 micrograms/mg wet wt. of skin, accompanied by formation de novo of the epidermal cis isomer. After sunlight irradiation, the content of the trans isomer decreased at a constant rate of 0.03 micrograms/mg wet wt. of skin per day, whereas the cis isomer was eliminated more quickly, having a phase of rapid decrease in the early period. From these results we suggest that compound (I) may participate in the metabolism of urocanic acid and natural thiol compounds such as cysteine and GSH.

Cysteine↗
PubMed1990

Embryonic mutation as a possible cause of in utero carcinogenesis in mice revealed by postnatal treatment with 12-O-tetradecanoylphorbol-13-acetate.

Although in utero irradiation at early stages induced a high incidence of somatic mutations at coat color genes in the embryos of a specified tester strain (PT x HT F1) of mice, it was not carcinogenic by itself. However, in utero-irradiated animals did develop skin tumors and hepatomas (but not leukemias) by the postnatal administration of 12-O-tetradecanoylphorbol-13-acetate. The incidence of both tumors and embryonic mutations increased with in utero doses of X-rays. Furthermore, a large reduction of tumor incidence, about 80%, was observed by low-dose-rate irradiation, similar to the 75% reduction in spot size found for embryonic mutations. The tumor nodule size was also dramatically reduced by low-dose-rate irradiation. Consequently, the induced incidence and size of tumors produced by 12-O-tetradecanoylphorbol-13-acetate treatment parallel those which are observed for coat color mutations as expected, because somatic mutations observed in the pigment cells must similarly occur in embryonic cells of other organs. The larger the clone of mutant cells, the greater their chance of becoming tumorigenic by 12-O-tetradecanoylphorbol-13-acetate posttreatment. These results strongly support the recent epidemiological survey showing that adult types of cancers, but not leukemias, are increasing in the atomic bomb survivors exposed in utero, since humans are continuously exposed to a variety of cancer-promoting agents in contrast to experimental animals reared without such exposures.

Animals↗
PubMed1990

Visualization of sialoglycoproteins in polyacrylamide gels by acidic ninhydrin reaction.

A new method for staining sialoglycoproteins in polyacrylamide gel after disc electrophoresis is described. The method utilizes the reaction of sialic acids with an acidic ninhydrin reagent which yields a stable color with an absorption maximum at 470 nm. After electrophoresis, the polyacrylamide gel is placed in a test tube and heated with 5 ml of the acidic ninhydrin reagent for 10 min in a boiling water bath. Sialoglycoproteins are detected as brown bands. No additional procedure such as destaining is necessary. When 20 micrograms fetuin, a sialoglycoprotein, per gel is applied, the band remains visible for at least 2 h. Stained gel can be scanned with a gel scanner at 470 nm. When the stained gel was dried on a sheet of polypropylene filter, the color was stable for at least one month. The present method is superior to the method using Stains-all (3,3'-diethyl-9-methyl-4,5,4',5'-dibenzothiacarbocyanine) in specificity and simplicity for the detection of sialoglycoproteins.

Electrophoresis, Polyacrylamide Gel↗
PubMed1990

Formation of sulfate from L-cysteine in rat liver mitochondria.

Formation of sulfate in rat liver mitochondria was studied. About 0.1 mumol of sulfate was formed in mitochondria from 1 g of liver in 60 min when 10 mM L-cysteine was used as the substrate. Addition of either 10 mM 2-oxoglutarate or 10 mM glutathione to this system increased sulfate formation 3 to 4 times. The addition of both 2-oxoglutarate and glutathione resulted in a 20-fold increase in sulfate formation. Sulfate formation in the presence of 5 mM L-cysteine was 58% of that with 10 mM L-cysteine. L-Cysteine-glutathione mixed disulfide was not a good substrate, indicating that this mixed disulfide was not an intermediate of sulfate formation in the present system. Incubation of 3-mercaptopyruvate with rat liver mitochondria also resulted in sulfate formation, and the addition of glutathione accelerated it. Formation of sulfite and thiosulfate was also detected. These results indicate that sulfate is produced in mitochondria, at least in part, from L-cysteine through the transamination pathway (3-mercaptopyruvate pathway).

Animals↗
PubMed1989

Direct determination of bound sialic acids in sialoglycoproteins by acidic ninhydrin reaction.

A simple and rapid method for sialic acid determination in sialoglycoproteins by acidic ninhydrin reaction is described. The method is based on the reaction of sialic acids with an acidic ninhydrin reagent (K. Yao and T. Ubuka (1987) Acta Med. Okayama 41, 237-241). By heating a sample solution containing sialoglycoprotein with the reagent at 100 degrees C for 10 min, a stable color with an absorption maximum at 470 nm was produced. The standard curve was linear in the range of 20 micrograms to 3 mg of fetuin, a sialoglycoprotein, per 3.0 ml of the reaction mixture. The reaction is specific only for sialoglycoproteins among various proteins examined. The acidic ninhydrin method was applied to the determination of sialic acids in sialoglycoproteins in ascites fluids of Ehrlich ascites tumor-bearing mice.

Animals↗
PubMed1989

[Prognostic significance of intra-arterial infusion chemotherapy in the treatment of locally advanced breast cancer].

Intra-arterial infusion chemotherapy of adriamycin (ADM) was performed in 31 cases with locally advanced breast cancer. The overall response rate for ADM was as high as 71% (22/31) in the primary lesions and histological response rate was obtained in 54.8% (17/31). Five-year survival rates for patients with stage IIIa, IIIb and IV breast cancer were 100%, 37.5% and 40.0%, respectively, compared with 63.8%, 35.7% and 12.5%, respectively, for 80 cases of control group. Although there was no correlation between local response rate and longer survival time, a more favorable prognosis seems possible with this treatment compared with other forms of therapy.

Adult↗