Search PubMed⌕ Search

Biomedical subjects

T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 181 records · Page 10Linked to original sources
PubMed1987

Immunosuppressive acidic protein in patients with testicular cancer.

Serum immunosuppressive acidic protein was compared to lactic dehydrogenase as a marker for testicular cancer in 54 patients with testicular cancer, 62 with benign urological diseases and 203 healthy controls. The mean value of serum immunosuppressive acidic protein in patients with testicular cancer (598 +/- 293 micrograms. per ml.) was statistically higher than that in patients with benign disease (429 +/- 163 micrograms. per ml.) and healthy controls (368 +/- 73 micrograms. per ml.). There were statistically significant differences in serum immunosuppressive acidic protein levels between controls and patients with stage 2 (p less than 0.0001) or stage 3 (p less than 0.001) testicular cancer, and between those with stage 1 and stage 2 (p less than 0.0001) or stage 3 (p less than 0.001) disease, respectively. The usefulness of immunosuppressive acidic protein as a marker for testicular cancer also was compared to that of lactic dehydrogenase. Immunosuppressive acidic protein and lactic dehydrogenase levels were elevated almost equally in patients with stage 2 or 3 disease (range 71 to 92 per cent). However, immunosuppressive acidic protein levels were elevated in only 3 of 25 patients with stage 1 cancer (12 per cent), compared to 11 of 25 (44 per cent) with elevated lactic dehydrogenase levels. Immunosuppressive acidic protein was correlated better with tumor stage. In conclusion, serum immunosuppressive acidic protein determinations may be useful in patients with testicular cancer for staging, monitoring treatment results and predicting recurrence.

Adult↗
PubMed1987

Characterization of a kidney antigen defined by a mouse monoclonal antibody K2.7.

Analysis by indirect immunoperoxidase staining of tissues demonstrated that monoclonal antibody (mAb) K2.7 derived from a mouse immunized with a renal cancer cell line OS-RC-2 was reactive with the tissues of all 36 normal kidneys examined, including two fetal kidneys, 22 of 25 renal cell carcinomas (RCCs) and one of 15 gastric cancers, but not with 23 normal tissues from 11 different organs or 41 malignant tissues from 10 different organs. mAb K2.7 was reactive with the kidneys of several animal species. Positive staining was seen on tubular epithelial cells of the kidney. Thus, the antigen recognized by mAb K2.7 appeared to be an interspecies kidney specific antigen. Results obtained by protein A (PA) assays with a cultured cell panel were consistent with those of staining and confirmed the restricted expression of the antigen. Immunochemical analysis revealed that mAb K2.7 reacted with molecules of 63,000, 60,000 and 43,000 daltons.

Animals↗
PubMed1987

In vitro intestinal microflora-mediated metabolism of biliary metabolites from 1-nitropyrene-treated rats.

To investigate the modifying role of the intestinal microflora in the metabolism of 1-nitropyrene (1-NP) via enterohepatic circulation, we collected bile from male Wistar rats administered [3H]1-NP orally. The bile was mixed with the intestinal contents (IC) prepared from untreated rats and the mixture was incubated anaerobically under an atmosphere of nitrogen at 37 C. Samples of the reaction mixture were removed at intervals to assay their mutagenic potential, to determine the radioactivity bound to the IC, and for analysis of the biliary metabolites. The binding of the radioactivity to the IC increased linearly as a function of time during the 1-hr incubation. The time-dependent binding does not occur with heat-treated IC and the binding was inhibited by addition of D-saccharic acid 1,4-lacton, a beta-glucuronidase inhibitor. The mutagenicity (for Salmonella typhimurium strain TA98 without S9 mix) of the bile increased early in the incubation period and then decreased very rapidly. The mutagenicity of the bile was also enhanced by treatment with a sonicated IC extract or beta-glucuronidase, but not with a heat-treated IC or aryl-sulfatase. The metabolites produced after the bile was incubated for short periods with the IC were mainly nitrohydroxypyrenes; at later times nitroreduction occurred. The level of acetylaminohydroxypyrenes, which were formed by deconjugation, did not change during the incubation. To determine the degree of contribution of the IC to the total acetylating capacity, we measured acetyltransferase activity of the IC and various organs in Wistar rats. The liver had the highest N-acetyltransferase activity among the seventeen organs examined. Considerable activity was also detected in the kidney, small intestine, lung, and testis, but the IC showed very low activity. The acetylating capacity of the IC was 0.27% of the total capacity in rats, and that of the liver was more than 80%. These results suggest that the nitrohydroxypyrenes formed from 1-NP in the liver were conjugated to glucuronic acid and excreted via the bile duct into intestine. Hydrolysis of these glucuronide conjugates by bacterial beta-glucuronidase liberated into intestine, free nitrohydroxypyrenes, which were direct-acting mutagens. The released aglycons were then rapidly nitro-reduced by intestinal microflora, but contribution of the intestinal microflora to acetylation of the reduced metabolites is very low.

Acetyltransferases↗
PubMed1987

Purification and characterization of a protease from Bacteroides gingivalis 381.

An intracellular membrane-free, trypsinlike protease was isolated from cells of Bacteroides gingivalis 381. The protease was extracted from the cells by ultrasonic treatment and was purified about 250-fold with a recovery of 2% by sequential procedures. The properties of the protease were as follows: its optimal pH was 8.5; its activity was almost completely lost on incubation at 50 degrees C for 15 min; its activity was inhibited by diisopropylfluorophosphate, p-toluenesulfonyl-L-lysine chloromethyl ketone hydrochloride, leupeptin, Mn2+, Cu2+, and Zn2+; it hydrolyzed casein, azocasein, N-alpha-benzoyl-DL-arginine-p-nitroanilide (BAPNA), bovine serum albumin, azocoll, and gelatin, but not N-alpha-benzoyl-DL-lysine-p-nitroanilide or human serum immunoglobulin A; its molecular weight was estimated as 45,000 by gel filtration and 50,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis; and its Km values for azocasein and BAPNA were 1.11% and 0.19 mM, respectively.

Bacteroides↗
PubMed1987

[A case of signet ring cell carcinoma of the urinary bladder].

A 51-year-old man was hospitalized with complaints of gross hematuria and terminal micturition pain. Cystoscopy revealed a low columnar tumor at the dome of the bladder. Ultrasonography and X-ray CT also demonstrated the same shape of tumor and no evidence of invasion to adjacent organs. Gastrointestinal examination, including upper gastrointestinal series and barium enema failed to reveal any primary tumor. The serum CEA level was 2.3 ng/ml, which was not elevated. Total cystectomy with ileal conduit and adjuvant chemotherapy consisting of cyclophosphamide, adriamycin and cisplatinum was performed. He died of a recurrent tumor 2 years and 2 months after the operation. Besides our experience of primary signet ring cell carcinoma of the urinary bladder, a review of the literature is reported.

Adenocarcinoma, Mucinous↗
PubMed1987

Genotoxicity of a variety of nitroarenes in DNA repair tests with human hepatocytes.

The genotoxicities of 8 nitroarenes, i.e., 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene, 2,7-dinitrofluorene, 3-nitrofluoranthene, 1-nitro-3-hydroxypyrene and 1-nitro-3-acetoxypyrene, were examined in DNA repair tests using human isolated hepatocytes. Out of the tested nitroarenes, 5 compounds, i.e., 1-nitropyrene, 1,3-dinitropyrene, 1,6-dinitropyrene, 1,8-dinitropyrene and 1-nitro-3-acetoxypyrene, clearly elicited positive responses of DNA repair. Among the chemicals which elicited positive responses, the levels of unscheduled DNA synthesis induced by the three dinitropyrene isomers were much higher than those of the other nitroarenes. Three chemicals, i.e., 2,7-dinitrofluorene, 3-nitrofluoranthene and 1-nitro-3-hydroxypyrene, elicited negative responses. The negative responses of 2,7-dinitrofluorene and 3-nitrofluoranthene, which had been positive in DNA repair tests with rodent hepatocytes, suggest some species differences between humans and rats in the metabolic activity of hepatocytes toward these agents.

Carcinogens↗
PubMed1987

Detection of mutagenic compounds in the urine of mice administered pyrene during exposure to NO2.

The urine of mice injected intraperitoneally with pyrene during exposure to NO2 was found to contain highly mutagenic compounds by means of the Ames test using Salmonella typhimurium strain TA98. The mice were exposed to 20 ppm NO2 for 3 days before intraperitoneal injection of pyrene (800 mg/kg of body weight). The pyrene-treated mice were further exposed to NO2 for an additional 24 hr, and the urine from the mice was collected in ice-cooled containers and stored frozen in the dark. The collected samples were treated with beta-glucuronidase and passed through activated Sep-Pack C18 cartridges. After elution with methanol, the effluent was concentrated and the residue was dissolved in dimethyl sulfoxide (DMSO). The DMSO solution was fractionated by high-performance liquid chromatography and the mutagenicity of each fraction was assayed with S. typhimurium strain TA98. The mutagenic compounds 3-hydroxy-1-nitropyrene, 6-hydroxy-1-nitropyrene, 8-hydroxy-1-nitropyrene, and 1-hydroxypyrene were identified in the mutagenic fractions by mass spectrometry and UV-visible spectrophotometry with synthetic reference substances. These mutagenic compounds may have been formed by either nitration of hydroxylated pyrene, or hydroxylation of 1-nitropyrene, which is formed in vivo from pyrene and NO2, or the simultaneous occurrence of these two reactions in the mouse body.

Animals↗
PubMed1987

[Review of ureteral carcinoma as seen in mapping of the cystectomized bladder].

The incidence of unexpected ureteral carcinoma on mapping and recurrence of upper urinary tract urothelial cancer was examined in 160 patients who had undergone total cystectomy for vesical cancer and complete mapping of the specimens between May, 1978 and June, 1986 at our Center. Unexpected carcinoma in the ureteral stump was found in 5 patients (3.1%) and recurrent cancer in the upper urinary tract developed in 2 (1.3%) of the 160 patients. The incidence was higher in the recurrent bladder cancer cases, and also higher in patients with non-visible, high grade and superficial tumors of the bladders.

Aged↗
PubMed1986

Induction of squamous cell carcinoma in the rat lung by 1,6-dinitropyrene.

The carcinogenicity of 1-nitropyrene [(1-NP) CAS: 5522-43-0] and 1,6-dinitropyrene [(1,6-DNP) CAS: 42397-64-8] was examined by their direct injection in a beeswax-tricaprylin vehicle into the lung of male F344/DuCrj rats. Of 28 rats given 0.15 mg of 1,6-DNP, 21 (75%) developed squamous cell carcinomas, 2 (7%) developed undifferentiated carcinomas, and 2 (7%) had squamous metaplasias in the lung by 72 weeks. In 32 rats that received 1.5 mg of 1-NP, neither carcinoma nor squamous metaplasia was induced. In all 19 rats (100%) given 0.5 mg of 3-methylcholanthrene [(MCA) CAS: 56-49-5], squamous cell carcinomas were induced earlier than in rats treated with 1,6-DNP. In 1 of 31 rats (3%) given the beeswax-tricaprylin vehicle only, squamous metaplasia was induced. Distant metastases of induced tumors were observed in 4 rats treated with 1,6-DNP and in 1 rat receiving MCA. Two lung tumors induced by 1,6-DNP were successively transplanted into the same strain of rats for 3 generations.

Animals↗
PubMed1986

Metabolic activation of 1-nitropyrene and 1,6-dinitropyrene by nitroreductases from Bacteroides fragilis and distribution of nitroreductase activity in rats.

Nitrated polycyclic aromatic compounds, 1-nitropyrene (1-NP) and 1,6-dinitropyrene (1,6-diNP), are environmental mutagens and carcinogens. Nitroreductases purified from an anaerobic bacterium, Bacteroides fragilis, catalyzed the metabolic activation of these compounds to produce DNA- and tRNA-bound adducts in vitro. Formation of the adducts was inhibited by p-chloromercuribenzoic acid, which is an inhibitor of nitroreductases from B. fragilis. The enzyme and coenzyme (NADPH) were essential for the adduct formation. These results suggest that nitroreduction is a necessary step in the metabolic activation of nitropyrenes. 1-NP bound specifically to poly(G) and poly(dG), and 1,6-diNP bound to poly(G), poly(dG), and poly(X). The other purine polynucleotides were weak acceptors. However, the reactive products of nitropyrenes formed by nitroreductases could not bind to pyrimidine polynucleotides. Enzymatic hydrolysis of 1-NP-bound DNA and subsequent analysis by high-performance liquid chromatography showed one major and two minor adducts in the hydrolysate. The peak of the major adduct corresponded to that of N-(deoxyguanosin-8-y1)-1-aminopyrene, which is the same as an adduct formed by xanthine oxidase, a mammalian nitroreductase. Nitroreductase activity in the various organs and intestinal contents of Sprague-Dawley rats was assayed in the presence of NADPH or NADH under nitrogen gas. Nitroreductase activity was widely distributed in the organs of the rats; in particular, that of the liver and of the small intestine was relatively high, but that of the respiratory organs such as lung and alveolar macrophages was very low. Intestinal contents had high nitroreductase activity, which was proportional to the number of bacteria, especially anaerobic bacteria, in the intestine. These results suggest that the nitroreductase activity of the normal bacterial flora is very high in rats and that the intestinal bacteria play a major role in the metabolism of nitropyrenes in vivo.

Animals↗
PubMed1986

Metabolism of 1-nitropyrene in germ-free and conventional rats.

The distribution, covalent binding and metabolism of radioactive 1-nitropyrene (1-NP) were examined following its oral administration to conventional and germ-free male Wistar rats. With both groups of animals, the liver, kidney, bladder, adipose tissue and gastrointestinal tract had the highest specific radioactivity. However, the maximum concentration of radioactivity occurred at 12 hr in conventional rats as compared to 24 hr in germ-free animals. This difference may be due to the faster transit time of the intestinal contents through conventional rats. At 48 hr after treatment, the covalent binding of 1-NP metabolites was greatest in liver and kidney of conventional rats, while in germ-free rats, substantial binding was also found in the gastrointestinal tract. The mutagenic activity in Salmonella typhimurium TA98 of fecal extracts and urine from conventional rats was greater in the presence of an S9 mix, whereas similar extracts from germ-free animals were more mutagenic in the absence of S9. The major fecal metabolites in germ-free rats were (in order of decreasing concentration): 3-nitropyrenol greater than 1-NP greater than 4,5-dihydroxy-4,5-dihydro-1-NP greater than 6-nitropyrenol greater than 8-nitropyrenol. With the exception of 1-NP, similar metabolites were found in the urine as their glucuronide conjugates. In the feces from conventional rats, substantial nitro reduction and N-acetylation occurred with the major metabolites being: 1-NP greater than 1-aminopyrene greater than 8-acetylaminopyrenol greater than 6-acetylaminopyrenol greater than 3-acetylaminopyrenol. The major metabolites identified in the urine from conventional rats were glucuronide conjugates of 6- and 8-acetylaminopyrenol, while the major biliary conjugates identified were glucuronide conjugates of 4,5-dihydroxy-4,5-dihydro-1-NP and 3-, 6-, and 8-nitropyrenol, although the relative proportion of glucuronide conjugates of 6- and 8-aminopyrenol and 6- and 8-acetylaminopyrenol increased in later stages of the biliary excretion. The polar and beta-glucuronidase-refractory metabolites, which may be sulfate and glutathione conjugates, remain to be identified.

Animals↗
PubMed1985

Human renal cell carcinoma: establishment and characterization of a new cell line (OS-RC-2).

A cell line, designated as OS-RC-2, has been established from a renal cell carcinoma in a 52-yr-old Japanese male patient and maintained for 23 mo. through 60 in vitro passages. The OS-RC-2 formed monolayers of polygonal epithelial cells and lacked contact inhibition. Doubling time of cells was about 60 h at the 30th passage. Electron microscopic findings indicated numerous long microvilli on the cell surface and many glycogen granules in the cytoplasm of this cell line, which are characteristic structures of renal cell carcinoma. Chromosomal analysis revealed that a small portion of this cell line had a hypodiploid modal number of 40 and a large portion had a hypotetraploid modal number of 75. The characteristics of the karyotype were one detected marker chromosome and the translocation between the Chromosomes 2 and 13. Cell line OS-RC-2 was serially transplantable into nude mice, and histopathological findings of heterotransplanted tumor showed a close similarity to those of the original tumor. Histocompatibility antigens of OS-RC-2 were HLA-A9, Bw52, which were identical to those of the peripheral blood lymphocytes of the patient.

Adenocarcinoma↗