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Biomedical subjects

T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 145 records · Page 8Linked to original sources
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↗
PubMed1991

[Clinical results of total prostatectomy].

Radical surgery was administered to 63 patients with prostatic carcinoma, of whom 48 were put under total prostatectomy, 13 under cystoprostatectomy and 2 under pelvic exenteration. Adjuvant therapy was given in three forms: pretreatment to 31 patients, castration to 44 patients and pelvic lymphadenectomy to 39 patients. The 7 patients in stage A survived without carcinoma. Of the 25 patients in stage B, recurrence was seen in 7 patients but there were no deaths and the 5- and 10-year cumulative survival rates were both 86%. Of the 24 stage C patients, 8 developed recurrence, 4 died with the disease, and the 5 and 10 year cumulative survival rates were 82% and 55% respectively. There were 7 stage D patients, of whom 3 developed recurrence and 2 died, and these patients had a 5 year cumulative survival rate of 86%. The results demonstrated that total prostatectomy with suitable adjuvant therapy is useful for advanced carcinoma as well as clinically early stage carcinoma.

Aged↗
PubMed1991

[Clinical study of incidental prostatic carcinoma].

At the Center for Adult Diseases, Osaka, between 1961 and 1987, 28 cases (1.8%) of incidental prostatic adenocarcinoma were detected by transurethral or subcapsular prostatectomy for clinically benign prostatic hypertrophy (1388 cases) and cysto-prostatectomy for urinary bladder carcinoma (156). Nine (32%) and 19 (68%) cases were in stages A1 and A2, respectively. Of the 19 A2 cases, 9 were well, 9 were moderately and 1 was poorly differentiated adenocarcinoma. Five of the A2 and 1 of the A1 progressed into clinical carcinoma, but none of these patients died of the cancer. Four of these 5 A2 patients had received no treatment postoperatively and one received castration. The intervals from diagnosis to progression ranged from 11 to 78 months. The survival rates at 5 and 10 years with A1 were 75% and 75%, and those with A2 were 80% and 37%. We conclude that the patients in stage A2 should be treated because stage A2 tumors, especially those with no treatment, progress at a higher frequency than stage A1 tumors.

Adenocarcinoma↗
PubMed1991

Treatment of metastatic renal cell carcinoma with a combination of human lymphoblastoid interferon-alpha and cimetidine.

Human lymphoblastoid interferon-alpha was administered intramuscularly at a dose of 5 x 10(6) units/day to 20 metastatic renal cell carcinoma patients. For potentiating the antitumor effect of interferon, cimetidine was also given to them orally at a dose of 800 mg/day. The combination therapy obtained a complete response in three patients (15%) and a partial response in three (15%). Nine patients (45%) had stable disease and five (25%), progressive disease. All six patients who responded to the combination therapy had been nephrectomized and had pulmonary metastases. Two of them also had metastases to other sites (mediastinal lymph nodes and bone). The pulmonary metastases were significantly more receptive to interferon therapy than those at the other sites. The average times before a response was obtained were 2.2 months for a minor response, 2.7 months for a partial response and 3.0 months for a complete response, and the average duration of response was 26 months. The six patients who responded survived for a significantly longer period than the 14 non-responding patients treated with interferon in combination with cimetidine. The major toxicities encountered were fever, fatigue and anorexia due to interferon, and the combination therapy was well tolerated except in three patients. The results suggest that interferon-alpha and cimetidine combination therapy may be of use in the management of patients with metastatic renal cell carcinoma.

Administration, Oral↗
PubMed1991

[Studies on the change in the levels of serum ferritin, serum iron and total iron binding capacity caused by aging and sex difference].

Sex difference and aging change of serum ferritin concentration in normal subjects were studied with their relations to serum iron concentration, total iron binding capacity (TIBC) and other hematological parameters. The subjects of this study were the stuff of our hospital (113 males and 330 females) and some old patients without having any diseases of internal medicine (11 males and 23 females), 477 in all. Serum ferritin level was 108.0 +/- 57.8 ng/ml in men and 26.4 +/- 22.7 ng/ml in women, which showed the significant difference between the sexes. In terms of the changes in serum ferritin level by aging, serum ferritin level increased with age from twenties to fifties in the men. On the other hand, it remained low in the women to their forties and its changes by aging were not observed, though it abruptly increased in the women after 50 years of age. The low levels of serum ferritin, iron, transferrin saturation (Fe/TIBC) and hemoglobin of red blood cell were often observed in the women aged from 18 to 45, but rarely found in the women after 50 years of age. According to this fact, the low level of serum ferritin in the young women are considered to be related to the menstruation. Significant correlation between serum ferritin and serum iron or transferrin saturation was shown both in men and women, while that between serum ferritin and hemoglobin of red blood cell was shown only in women.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1990

Nitro reaction in mice injected with pyrene during exposure to nitrogen dioxide.

We have previously reported that the beta-glucuronidase-treated urine of mice injected intraperitoneally with pyrene during exposure to NO2 contained highly mutagenic compounds such as nitropyrene metabolites when tested by the Ames assay using Salmonella typhimurium strain TA98. In the present study, we found that the formation of these mutagens was dose-dependent between 10 and 200 mg of pyrene per kg of body weight at 5 and 10 ppm of NO2. Further, to elucidate the substrate of nitration in vivo, we injected 1-hydroxypyrene, which is the metabolite of pyrene, to mice intraperitoneally during exposure to NO2. Since the results were the same as those obtained by injection with pyrene, we suggest that the pyrene was not nitrated directly but after its hydroxylation.

Animals↗
PubMed1990

Biliary excretion of glutathione conjugates of 4,5-epoxy-4,5-dihydro-1- nitropyrene and 9,10-epoxy-9,10-dihydro-1-nitropyrene in rats administered 1-nitropyrene orally and their further metabolism in the intestinal tract.

1-Nitropyrene (1-NP), a mutagenic and carcinogenic substance that occurs in the environment, is metabolized by reductive and oxidative pathways. 4,5-Epoxy,4,5-dihydro-1-NP (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-NP (1-NP 9,10-oxide) are oxidatively activated metabolites of 1-NP, and react with glutathione. HPLC analysis of biliary metabolites from rats administered [3H]1-NP orally showed the presence of glutathione conjugates of 1-NP 4,5-oxide and 1-NP 9,10-oxide and their metabolites, cysteinylglycine and cysteine conjugates. During the 48 h following [3H]1-NP administration, 21.4% of the biliary metabolites were excreted as glutathione, cysteinylglycine and cysteine conjugates of 1-NP oxides. The proportions of glutathione conjugates of 1-NP 4,5-oxide and 1-NP 9,10-oxide were 2.6 and 10.4% respectively. Bile and pancreatic juice collected from normal rats metabolized glutathione conjugates of 1-NP oxides and produced the corresponding cysteinylglycine and cysteine conjugates. In particular, the gamma-glutamyltransferase activity of pancreatic juice was markedly high. When glutathione conjugates of 1-NP oxides were incubated with a cell-free extract of small intestinal contents, they decreased rapidly and cysteine conjugates increased via cysteinylglycine conjugates, indicating that pancreatic juice plays an important role in the small intestine for the metabolism of glutathione conjugates to corresponding cysteine conjugates. Although degradation activity of small intestinal contents for cysteine conjugates was very low, degradation activity of the contents of the cecum and large intestine was high and was inhibited by an inhibitor of cysteine conjugate beta-lyase (beta-lyase) activity, aminooxyacetic acid. Furthermore, the intestinal anaerobic bacteria Peptostreptococcus magnus and Eubacterium limosum showed high beta-lyase activity, suggesting that the cysteine conjugates might be further metabolized by beta-lyase of the normal bacterial flora in the lower intestine to the reactivated metabolites and reabsorbed.

Administration, Oral↗