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T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 19 recordsLinked to original sources
PubMed1992

Decomposition of linear dodecylbenzenesulfonate by simultaneous treatment with ozone and ultraviolet irradiation: rapid disappearance of formed mutagens.

The decomposition products and mutagenic activity in Salmonella typhimurium strains TA98, TA100 and TA104 in the presence and absence of S9 mix of linear dodecylbenzenesulfonate (DBS) in aqueous solution after ozone treatment alone or simultaneous treatment with ozone and ultraviolet (UV) irradiation (ozone/UV treatment) were investigated. The decomposed DBS solutions after these treatments for 4 h were mutagenic for strains TA98, TA100 and TA104 both with and without S9 mix, but this mutagenicity disappeared rapidly during further ozone/UV treatment. Mutagenicity of the decomposed solution of DBS, however, was not substantially decreased by treatment with ozone alone. Formaldehyde and glyoxal were identified as the decomposition products of DBS in water by high-performance liquid chromatography after treatment with 2,4-dinitrophenylhydrazine. Although these two compounds were mutagenic for strain TA104 both with and without S9 mix, they disappeared after further ozone/UV treatment but not after ozone treatment alone. These results indicate that ozone/UV treatment is an effective procedure for purifying drinking water.

Benzenesulfonates↗
PubMed1992

Role of intestinal microflora in metabolism of glutathione conjugates of 1-nitropyrene 4,5-oxide and 1-nitropyrene 9,10-oxide.

DNA adduct formation in the liver of B6C3F1 mice after administration of 1-nitropyrene (1-NP) was shown by the 32P-postlabeling technique. The major adduct was not N-(deoxyguanosin-8-yl)-1-aminopyrene, which was easily formed in in vitro nitroreduction of 1-NP in the presence of DNA, but the major spots migrated to the same position as the in vitro DNA adduct spots of K-region epoxides of 1-NP (1-NP 4,5- and 9,10-oxide). 1-NP oxides formed by the oxidative activation of 1-NP in the liver were excreted into the bile as detoxified glutathione conjugates which were changed to cysteine conjugates in the upper intestinal tract. The cysteine conjugates were degraded by cysteine conjugate beta-lyase (beta-lyase) of intestinal microflora in the lower intestinal tract. The mutagenicity of cysteine conjugates of 1-NP oxides for Salmonella typhimurium was enhanced by addition of beta-lyase and was decreased by addition of aminooxyacetic acid, a beta-lyase inhibitor. The in vitro binding of the cysteine conjugates to calf thymus DNA was increased by addition of beta-lyase and xanthine oxidase. We administered glutathione conjugates of 1-NP oxides to two groups of mice that had been treated with antibiotics or saline by gavage and analyzed the DNA adducts in the lower intestinal mucosa. The specific DNA adducts were detected in the saline-treated group but not in the antibiotics-treated group. These results suggest that intestinal microflora play an important role in activation of glutathione conjugates of 1-NP oxides.

Animals↗
PubMed1992

Carcinogenicity examination of 1-nitropyrene oxides and related chemicals: lack of their tumorigenic effects in a newborn mice assay.

Carcinogenicity of 1-nitropyrene (NP) oxides (1-NP 4, 5-oxide and 1-NP 9, 10-oxide) and related chemicals (1-NP and 1-nitro-6-hydroxypyrene) was examined in the newborn mouse model by i.p. administration at 1, 8, 15 days after birth (each chemical was given at a total dose of 700 nmol per mouse). Low incidences of hepatocellular neoplasms were recognized in male mice exposed to either of these chemicals. However, the incidences were not significantly different from those of animals given solvent alone or of non-treatment. Lymphoma was infrequently seen in female mice given some of tested chemicals. The incidences were also not significantly different from those of mice with the solvent alone or of the controls. The results suggest that although these aromatic hydrocarbons exert genotoxicity or mutagenicity, they may not be potent carcinogens, or the assay with use of newborn mice may be insufficient to monitor carcinogenicity of such chemicals.

Adenoma↗
PubMed1992

[Surveillance after orchiectomy for stage I testicular seminoma].

The results of treatment by orchiectomy and radiotherapy for stage I testicular seminoma are excellent with cure rates exceeding 95% and relapse rates less than 5%. However, after the development of successful surveillance programs for stage I nonseminomatous testicular cancers, the role of radiotherapy has been questioned by some authors and they proposed a "surveillance policy" for these patients. The purpose of this study was to determine the percentage of patients cured by orchiectomy alone, percentage who ultimately required therapy for occult metastases, site of recurrence, and over-all cure rate and treatment morbidity. And these data were compared with those of adjuvant radiotherapy group retrospectively. Twenty seven patients were treated with adjuvant radiotherapy (RT group). Since 1986, 23 patients with stage I testicular seminoma entered the "surveillance only" protocol at our institution (S group) with a follow-up between 14 and 70 months (median 43 months). Informed consent for the policy of surveillance was obtained. Follow up consisted of physical examination, determination of serum tumor markers and chest X-ray bimonthly for 2 years, every 3 months for 1 year, every 6 months for 2 years and annually thereafter to 10 years. CT scans were performed every 4 months for 3 years, every 6 months for 2 years. Two patients in S group (8.7%) relapsed at 4 and 7 months after orchiectomy with nonbulky retroperitoneal disease (less than 5 cm in diameter), whereas only 1 (3.7%) irradiated patients did so after 4 months.

Adult↗
PubMed1992

[Renal cancer specific antitumor activities of a mouse monoclonal antibody K2.7 to human renal cell carcinoma].

We have prepared a mouse monoclonal antibody (mAb) K2.7 (IgG3) by immunizing mice with renal cancer cell (RCC) line OS-RC-2. In a serological analysis by protein A assay, 25 out of 31 RCC lines reacted with the mAb K2.7 but none of the 50 other cell lines from different organs except for 2 cell lines did. In immunohistological analysis by indirect immunoperoxidase assay, 66 out of 72 renal cancer tissues showed positive staining. Metastatic lesions of renal cancers also reacted similarly to the primary lesion. Some restricted normal tissues including tubules of normal kidney showed positive staining. Specific antitumor activities of mAb K2.7 against RCC lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell mediated cytotoxicity (ADCC) assays. In CDC assay, all of the 9 RCC lines were killed by mAb K2.7 and normal human serum, and killing activities of mAb K2.7 presumably depend on the number of antibody molecules bound to the cell surface. Sera from 9 patients with renal cancers including low and high stages showed the same killing activities to 3 RCC lines as normal human serum. In the ADCC assay, peripheral leukocytes (PBLs) from 4 healthy donors showed strong killing activities to RCC lines. Killing activity differed with the individual. PBLs from the same 9 patients as in the CDC assay showed significantly positive killing activity against 3 RCC lines. These findings suggest the usefulness of mAb K2.7 for the specific immunotherapy of renal cancer.

Antibodies, Monoclonal↗
PubMed1992

[Surgical treatment under extracorporeal circulation for renal cell carcinoma with tumor thrombus in inferior vena cava].

Three cases of renal cell carcinoma with tumor thrombus extending into the inferior vena cava are reported. Radical nephrectomy and thrombectomy were performed under extracorporeal circulation in all the cases. The level of tumor thrombus was preoperatively determined by computed tomography, magnetic resonance imaging or venacavography. The tumor thrombus extended into the right atrium in one, and above the hepatic vein in two cases. One patient whose thrombus reached the right atrium died of multiple metastasis of renal cell carcinoma 5 months after operation. Another patient with lung metastasis was given interferon-alpha and is alive 5 months after operation. The other patient is clinically free of disease and in good health 7 years after operation. We believe that extracorporeal circulation allows an opportunity to resect the tumor thrombus in a controlled situation, and makes the operation safer.

Aged↗
PubMed1991

Species differences in metabolic activation and inactivation of 1-nitropyrene in the liver.

To extrapolate from animal studies to humans the risk of 1-nitropyrene (1-NP), we determined the differences between human and experimental animals in oxidative activation of 1-NP to 1-NP oxides and inactivation of 1-NP oxides by epoxide hydration and glutathione conjugation in hepatic subcellular fractions from 6 species including humans. Species differences were found in both activation of 1-NP and inactivation of 1-NP oxides. 1-Nitro-4,5-dihydro-4,5-epoxypyrene-producing activity was highest in guinea pig and dog, followed by hamster, rat, human, and mouse. 1-Nitro-9,10-dihydro-9,10-epoxypyrene-producing activity was highest in hamster, followed in order by guinea pig, rat, dog, mouse, and human. The ratio of 1-nitro-4,5-dihydro-4,5-epoxypyrene to 1-nitro-9,10-dihydro-9,10-epoxypyrene also varied with the animal species. Hydration of 1-nitro-4,5-dihydro-4,5-epoxypyrene was highest in human, followed by dog, guinea pig, hamster, rat, and mouse. 1-nitro-9,10-dihydro-9,10-epoxypyrene was a poor substrate for epoxide hydrolase in all species. Glutathione conjugation of 1-NP oxides in rodents was higher than that in human and dog. In humans, hepatic microsomes produced the lowest level of 1-NP oxides but hydrolyzed them most efficiently, and glutathione conjugation activity of the cytosol was as low as in dogs, and there was a wide degree of interindividual variations in these activities. No single species studied was a good model for humans, and the balance of activation/inactivation tends toward detoxification in these adult animals.

Animals↗
PubMed1991

Genotoxicity of pyrene oxide and 1-nitropyrene oxides in hepatocyte primary culture/DNA repair test.

The genotoxicity of a pyrene oxide, 1-nitropyrene (NP) oxides and other related compounds was examined in the hepatocyte primary culture (HPC)/DNA repair test. Pyrene 4,5-oxide and both 1-NP-4,5-oxide and 1-NP-9,10-oxide elicited clearly positive responses of DNA repair. In this assay, 1-NP itself was weakly positive. However, other related chemicals such as pyrene, 1-nitro-3-hydroxypyrene, 1-nitro-6-hydroxypyrene, and 1-nitro-8-hydroxypyrene did not generate positive responses.

Animals↗
PubMed1991

Comparison between DNA adduct formation and tumorigenesis in livers and bladders of mice chronically fed 2-acetylaminofluorene.

Female BALB/c mice continuously fed 2-acetylaminofluorene (AAF) develop liver and bladder tumors. The incidence of liver tumors is linearly related to the carcinogen concentration in the diet, while the tumor response in the bladder is markedly non-linear. In the current experiments, liver and bladder DNA adducts were measured in female BALB/c mice fed several different concentrations of AAF for 28 days. The adduct concentrations were then compared to the previously reported incidences of neoplastic and preneoplastic lesions in these tissues. In initial experiments, mice were fed either 30 or 150 mg [ring-3H]AAF/kg diet for 21 days. Liver DNA adducts were identified by HPLC, which indicated the presence of one major adduct, N-(deoxyguanosin-8-yl)-2-aminofluorene (dG-C8-AF). This adduct was also the major product detected by 32P-postlabeling in liver and bladder DNA from mice fed the same concentrations of AAF for 28 days. Radioimmunoassays, conducted with an antibody specific for dG-C8-AF, showed that steady-state concentrations of dG-C8-AF were obtained at 28 days of AAF feeding; thus, this time point was used to determine the relationship between the dose of AAF and the adduct levels. In mice fed nine concentrations of AAF (5-150 mg AAF/kg diet), the adduct concentrations after 28 days of feeding were linearly related to dose in both the liver and bladder, with the adduct concentration being approximately 3-fold greater in the bladder. These results indicate that a linear correlation exists between the hepatic concentration of dG-C8-AF and the liver tumor incidence. In the bladder however, a linear relationship was not observed, which suggests that additional tissue-specific factors, such as toxicity, are essential components for tumorigenesis in this tissue.

2-Acetylaminofluorene↗
PubMed1991

Tumor promoting potential in male F344 rats and mutagenicity in Salmonella typhimurium of dipyrone.

For assessment of the carcinogenic potential and the mutagenicity of dipyrone, an antipyretic anodyne, -[(2,3-dihydro-1,5-dimethyl-3-oxo-2-phenyl-1H-pyrazol-4-yl) methylamino]-methanesulfonic acid sodium salt monohydrate, three experiments were conducted using dipyrone A produced in Japan and/or dipyrone B obtained from the Federal Republic of Germany. (i) Carcinogenic potential of dipyrone A for rat liver: 8 week old male F344 rats were pretreated with 0.01% diethylnitrosamine (DEN) in drinking water for 2 weeks and, after 1 week of resting, administered 0.4% dipyrone in drinking water, 5 days a week, for 72 weeks. After an 8 week recovery period, all surviving rats were killed at 83 weeks. Hepatocellular carcinomas developed at a higher incidence in the DEN + dipyrone group (18 of 29 rats, 62%) than in the DEN alone group (9 of 29 rats, 31%), the difference being statistically significant (P less than 0.05). No carcinogenic activity of dipyrone was demonstrated in the groups given 0.4% dipyrone for 72 weeks or 0.4% dipyrone for 25 weeks, followed by 0.05% phenobarbital (PB) for 50 weeks. However, glutathione S-transferase P positive (GST-P+) preneoplastic hepatic foci in these groups were observed at a higher incidence than in the untreated control group (P less than 0.01). (ii) Effect of dipyrone A and dipyrone B on induction of DEN-initiated GST-P+ hepatic foci in a medium-term bioassay system: 0.4% dipyrone A in drinking water and 0.57% dipyrone A or dipyrone B in powdered diet after DEN initiation had similar enhancing effects on the development of GST-P+ foci (P less than 0.001). (iii) The Ames mutation test in Salmonella: both dipyrone A and dipyrone B proved weakly mutagenic for strain TA100 in the presence or absence of S9 fraction.

Animals↗
PubMed1991

Isolation, and morphological and chemical properties of an autolysis-deficient mutant of Clostridium botulinum type A.

An autolysis-deficient mutant was isolated from Clostridium botulinum type A 190L by treatment with ethyl methanesulfonate. The cell wall prepared from the mutant autolyzed at much slower rate than that from the parent strain, accompanying with much less liberation of both amino terminals and reducing groups. Electron microscopic observation revealed that the mutant strain was converted to short rod or curved spherical form with thickened cell walls when the growth temperature was shifted from 37 to 45 C. The mutant had a significantly larger amount of non-peptidoglycan-carbohydrate complexes than did the parent strain and became markedly resistant to the autolysin partially purified from the parent, compared with the parent strain. Furthermore, the mutant was fairly tolerant to killing by penicillin. These results suggest that the autolysis deficiency of the mutant was due not only to the deficient production of autolysin but also to the excess accumulation of carbohydrate in the cell wall.

Animals↗
PubMed1991

[Combination chemotherapy with ifosfamide (or cyclophosphamide), adriamycin, cis-platinum and peplomycin (IAPP) for hormonally resistant metastatic prostatic cancer].

From January, 1986 to April, 1990, combination chemotherapy with ifosfamide (or cyclophosphamide), adriamycin, cis-platinum and peplomycin was performed in 15 patients with hormonally resistant metastatic adenocarcinoma. Three patients had partial response (PR) and 9 remained objectively stable (ST). The median response duration of PR + ST (12) was 5.7 months (range 2.8 to 18.0+). Three patients progressed while on this therapy. Of 8 patients with prior treatment of chemotherapy or chemo-hormonal therapy, 6 achieved an objective response (2 PR, 4 ST). Severe toxicities occurred in 2 patients. One died of lung fibrosis induced by peplomycin and the other received urinary diversion for persistent hemorrhagic cystitis. These results compare favorably with previous reports of chemotherapy treatment of metastatic prostatic cancer patients who failed on hormonal manipulation. However, careful treatment is needed for lung fibrosis and hemorrhagic cystitis.

Aged↗
PubMed1991

[Incontinent urinary diversion].

We analyzed 237 patients who underwent total cystectomy with ileal conduit urinary diversion or cutaneous ureterostomy at the Center for Adult Diseases, Osaka. One-hundred and eighty-eight patients underwent ileal conduit diversion and 49 patients underwent cutaneous ureterostomy. No patient died within 30 days after the operation, but two patients who underwent ileal conduit diversion died of postoperative complications within 2 months. Early complications occurred in 94 patients (50%) in the ileal conduit group and in 18 patients (37%) in the ureterostomy group. Late complications occurred in 85 patients (45%) in the ileal conduit group and in 23 patients (47%) in the ureterostomy group. Frequent early complications in the ileal conduit group were wound infection (29%), and intestinal complications (13%) which included ileus and upper urinary tract complications (12%). The most frequent late complications were stomal complications (26%) which included peristomal dermatitis stomal stenosis, parastomal hernia, and stomal prolapse, and upper urinary tract complications which were noted in 27 patients (14%).

Aged↗