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Biomedical subjects

T Kinouchi

Publications and source records attributed to T Kinouchi.

At least 91 records · Page 5Linked to original sources
PubMed1996

Mutagenicity of chemicals produced from sodium dodecylbenzenesulfonate by treatment with ozone and ultraviolet irradiation.

The interaction of formaldehyde and glyoxal produced from linear dodecylbenzenesulfonate (DBS) in aqueous solution after simultaneous treatment with ozone and ultraviolet (UV) irradiation and the effect of DBS on the mutagenic activity of formaldehyde and glyoxal were investigated. The decomposition of DBS in aqueous solution resulted in the formation of the mutagens formaldehyde and glyoxal as intermediate products after the simultaneous treatment for 4 hr. Therefore, the aqueous solution containing decomposed DBS after the treatment for 4 hr was mutagenic for Salmonella typhimurium strains TA100 and TA104 in the presence and absence of S9 mix. However, the mutagenic activity was greater than the sum of the mutagenic activity of formaldehyde and glyoxal formed from DBS. The aqueous solution mixed with formaldehyde and glyoxal did not increase the mutagenicity above the sum of the mutagenic activity in the presence or absence of DBS. Furthermore, DBS at concentrations of 2.0 micrograms/plate or less did not affect the mutagenicity of the mixtures containing formaldehyde and glyoxal. In addition, there was little bacteriocidal effect of the mixed solution on the mutagenicity test strains. These results suggest that unidentified mutagenic intermediate products were produced from DBS after simultaneous treatment with ozone and UV irradiation for 4 hr.

Animals↗
PubMed1996

Giant hydronephrosis of bilateral duplex systems associated with ureteral ectopia: a case report.

Giant hydronephrosis is an uncommon clinical entity. Even more uncommon is the association of giant hydronephrosis with a double collecting system and ectopic ureter. Here, we report a case of giant hydronephrosis of the bilateral duplex systems associated with ureteral ectopia. The patient underwent upper pole nephrectomy and upper ureterectomy. To our knowledge, only four similar cases have been reported previously.

Adult↗
PubMed1996

[Neoadjuvant endocrine therapy in patients with locally advanced prostate cancer].

Recently, there has been an increasing interest in the application of preoperative endocrine therapy prior to radical prostatectomy. The main purpose of this treatment modality is to enhance surgical curability and increase survival. Endocrine therapy was performed before radical prostatectomy on 40 patients between 1986 and 1993; 15 had stage B2 and 25 had stage C disease. The median duration of preoperative endocrine therapy was 3.8 months. All patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was on average a 25.5% (0-71.8%) decrease in maximal cross-sectional area of prostate gland as determined by transrectal ultrasonography. Treatment-related histological effects, divided into three grades were as follows; excellent in 17, moderate in 11 and poor or no regression in 12. Pathological downstaging of disease status from the diagnosis made at the initial clinical examination was seen in 13 of the 40 patients (33%). At a median follow-up of 50 months (19-118 months), 36 of the 40 patients are disease-free and two died of cancer 43 and 50 months postoperatively. These findings suggest that preoperative endocrine therapy plays an important role in the management of locally advanced prostatic cancer.

Aged↗
PubMed1996

[Prostatic cancer with cystic formation: a case report].

A 60-year-old man was admitted to our hospital with the chief complaints of dysuria and sense of abdominal fullness. On digital rectal examination, an enlarged prostate with a smooth surface and elasticity was palpated. The concentration of prostate specific antigen (PSA) was elevated to 78 ng/ml. Pelvic computed tomographic (CT) scan and magnetic resonance imaging (MRI) revealed a large prostate, 8 cm in diameter, with a cystic mass, and extra-iliac lymph node swelling. On needle biopsy of the prostate and cyst, the histology was poorly differentiated adenocarcinoma, and the aspirate comprised bloody fluid with a negative test for cytology. He was diagnosed with prostatic cancer of T4N3M0. This is the 19th case of prostatic cancer with cystic formation reported in Japan.

Adenocarcinoma↗
PubMed1995

Mucosa-preferential DNA adduct formation by 2-amino-3-methylimidazo-[4,5-f]quinoline in the rat colonic wall.

The mechanism of mucosa-specific formation of DNA adducts, which was found recently in human intestines, was studied in male F344 rats treated with 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). There are three conceivable pathways for p.o. administered IQ to reach the target colonic mucosal cells: pathway 1, through the digestive canal which exposes from the lumenal direction; pathway 2, following enterohepatic circulation re-expose from the lumenal direction; and pathway 3, exposure via blood circulation. To investigate these possible pathways, the following surgical procedures were performed: (a) portal catheterization for IQ administration to eliminate pathway 1 and (b) choledochal catheterization for bile drainage to eliminate pathway 2. When both procedures are combined, only pathway 3 is active. Four types of IQ-DNA adducts were commonly observed in the colons of all experimental groups, with no qualitative difference between the mucosal and muscular layers. When IQ-HCl was administered by p.o. gavage at a dose of 100 mumol/kg body weight, approximately 70% of the IQ-DNA adducts in the colonic mucosa (13.1 +/- 4.3 adducts/10(7) nucleotides) was induced through pathway 1. Pathway 3 induced the remaining 30% of mucosal adducts, producing equal adduct levels in both layers. Pathway 2 did not work for adduct formation. The DNA adduct formation was unaffected in the presence of intestinal flora, indicating that detoxified IQ does not reactivate by floral enzymes. In conclusion, mucosa-specific DNA adduct formation in the colon is caused most likely by the absorption of carcinogens through the lumen.

Animals↗
PubMed1995

Conventional protein kinase C (PKC)-alpha and novel PKC epsilon, but not -delta, increase the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein from PKC cDNA transfected 3Y1 fibroblasts.

A large soluble N-terminal fragment of Alzheimer's disease amyloid precursor protein (secreted form of APP: APPs) is produced by constitutive processing in the middle of the amyloid beta-protein portion of APP. Recent studies indicate that the activation of endogenous protein kinase C (PKC) with phorbol ester raises the rate of secretion of APPs. We constructed rat fibroblast 3Y1 cells that stably overexpress PKC isoenzymes alpha, delta, or epsilon, and analyzed the amount of APPs released from these PKC transfectants. The levels of APPs released from 3Y1 cells overexpressing PKC alpha and -epsilon were higher than those from PKC delta-transfected and control cells expressing vector only. These results suggest that specific isoforms of PKC regulate the secretion of APPs through a signaling pathway.

Alzheimer Disease↗
PubMed1995

Arachidonate metabolites affect the secretion of an N-terminal fragment of Alzheimer's disease amyloid precursor protein.

Amyloid precursor protein (APP) is degraded within the amyloid beta-protein (A beta) domain and its large soluble N-terminal fragment (secreted form of APP: APPs) is secreted into the culture media of many kinds of cells. We report here a quantitative increase in APPs secretion in the medium of human glioblastoma A172 cells grown under serum-free conditions. When A172 cells were treated with inhibitors of the arachidonate cascade, a modulation of APPs secretion was observed; the addition of small amounts of indomethacin increased secretory cleavage, but higher doses suppressed it. Nordihydroguaiaretic acid (NDGA), an inhibitor of lipoxygenases, also inhibited APPs secretion. These results suggest that arachidonate metabolites of the leukotriene pathway may promote APPs release upon extracellular signaling via a signal transduction pathway, while metabolites of the prostaglandin pathway inhibit APPs secretion.

Amyloid beta-Peptides↗
PubMed1995

Mutagenicity of soy sauce treated with nitrite in the presence of ethanol or alcoholic beverages.

The mutagenicity induced by soy sauce after reaction with 50 mM nitrite at pH 3, 37 degrees C, for 60 min in the presence of 1.25-10% ethanol was reduced in proportion to the ethanol concentration. The mutagenicity of soy sauce treated with nitrite was also reduced in the presence of commercial alcoholic beverages, Japanese sake, wine, 'shochu', whiskey and brandy, but not beer, in proportion to the concentration. The mutagenicity of nitrite-treated tyramine, which is a major precursor of a mutagen in soy sauce treated with nitrite, was strongly reduced in the presence of ethanol, n-propanol or isopropanol and more strongly reduced in the presence of methanol, but was increased twofold in the presence of the sugars glucose or sucrose. The reduction of the mutagenicity of nitrite-treated tyramine required simultaneous treatment of tyramine with ethanol and nitrite. The mutagenicity of tyramine treated with nitrite was clearly reduced in the presence of shochu and whiskey, similarly to ethanol. Analysis by high-performance liquid chromatography revealed that the reduction of the mutagenicity of nitrite-treated tyramine in the presence of ethanol resulted from the reduced production of mutagenic 3-diazotyramine from tyramine.

1-Propanol↗
PubMed1995

Stability of 1-nitropyrene and 1,6-dinitropyrene in environmental water samples and soil suspensions.

This study examined the stability of mutagenic 1-nitropyrene (1-NP) and (1,6-dinitropyrene (1,6-diNP) in environmental water samples and various soil suspensions containing 0.1% peptone and in water samples containing no peptone. The water samples or the soil suspensions were mixed with NPs and incubated at 30 degrees C. The stability of NPs was expressed as mutagenic activity remaining in the test solutions. The mutagenicity decreased rapidly when 1-NP or 1,6-diNP was incubated in unautoclaved test solutions containing 0.1% peptone but not when incubated in autoclaved test solutions. The mutagenicity in the soil suspensions, especially in the sludge, decreased faster than in the water samples. This was due to the large number of colony-forming units (CFU) in the soil suspensions. In the water samples containing 0.1% peptone, the mutagenicity of NPs in the polluted Tamiya River water decreased faster than in the unpolluted Yoshino River water. The rate of decrease was dependent on the number of CFU in the water samples. A large number of CFU decreased the mutagenicity more rapidly than did a small number of CFU in samples. The disappearance of mutagenicity was dependent on the initial concentrations of NPs. The periods required for a 50% decrease in the mutagenicity of 1-NP at the low concentration (0.2 microgram/ml) was shorter than that at the high concentration (3 micrograms/ml). 1-Aminopyrene was detected in the 1-NP test solution after incubation when it was analyzed by high-pressure liquid chromatography. In the water samples containing no peptone, the mutagenicity of 1-NP (0.2 microgram/ml) decreased gradually during 30 days of incubation. After incubation for 1540 days, the remaining mutagenicity of 1-NP in the water samples was almost the same as that in autoclaved water samples. On the other hand, the mutagenicity of 1,6-diNP (10 ng/ml) decreased and the remaining mutagenicity, except in the Yoshino River water, was less than 20% after 30 days of incubation and was completely lost during the 1540-day incubation. However, the mutagenicity of 1,6-diNP in autoclaved water samples was very stable and almost all mutagenicity, except in sea water, remained after 1540 days of incubation at 30 degrees C. These results suggest that the microflora in the environment plays an important role in the primary degradation and decontamination of relatively low concentrations of NPs.

Biodegradation, Environmental↗
PubMed1995

Molecular cloning of the leuB gene from Bacteroides fragilis by functional complementation in Escherichia coli.

Clones containing the Bacteroides fragilis leuB-complementing gene were isolated by screening of a B. fragilis genomic library constructed in Escherichia coli. One recombinant clone, designated pOT865, with the smallest DNA insert (4.5 kb) could complement three independent leuB mutations in E. coli and the leuB-complementing determinant in pOT865 was localized to a region of 1.5-kb DNA. The results of Southern blot analysis suggested that a single copy of the cloned gene was present in the B. fragilis genome. The cloned fragment appeared to contain a sequence that could function as promoter in E. coli and direct the synthesis of a 42-kDa protein. These results suggest that the cloned segment contains the structural gene for beta-isopropylmalate dehydrogenase (leuB).

3-Isopropylmalate Dehydrogenase↗
PubMed1995

Purification and characterization of a fibrinogen-degrading protease in Bacteroides fragilis strain YCH46.

A novel fibrinogenolytic protease was purified from Bacteroides fragilis strain YCH46. The protease was extracted from cells by ultrasonic treatment and was purified 425-fold with a recovery of 2.1% by sequential procedures using azocasein as a substrate. The purified protease showed a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis with an estimated molecular weight of 100 kDa, which was consistent with the value obtained by gel filtration, indicating a monomeric native structure. Its optimal pH, Km, and Vmax for azocasein were 7.5, 0.2%, and 286 U/min/mg, respectively. The protease activity was completely inhibited by addition of 1 mM Hg2+, Cu2+, Zn2+, diisopropyl fluorophosphate, N-ethylmaleimide or p-chloromercuribenzoate but not by the inhibitors of metalloprotease or aspartic protease, suggesting that the enzyme is a serine-thiol-like protease. The protease hydrolyzed azocasein, casein, fibrinogen, gelatin, and azocoll, but not bovine serum albumin, ovalbumin, fibrin, fibronectin, immunoglobulins, transferrin, hemoglobin or types I, III, and IV collagen. The enzyme also hydrolyzed the chromogenic substrates alanyl-alanine p-nitroanilide, L-valyl-alanine p-nitroanilide, alanyl-alanyl-valyl-alanine p-nitroanilide, and glycyl-proline p-nitroanilide, but was inert toward L-alanine p-nitroanilide, alanyl-alanyl-alanine p-nitroanilide, and N-alpha-benzoyl-DL-arginine p-nitroanilide. The protease completely hydrolyzed the alpha-chain of fibrinogen at 37 C within 10 hr and at the same time the time required for clotting of protease-treated fibrinogen by thrombin was prolonged. The fibrinogenolytic activity of a crude extract of B. fragilis was stronger than that of other species of the Bacteroides fragilis group tested: B. ovatus, B. distasonis, B. eggerthii, B. uniformis, and B. thetaiotaomicron. These results suggest that the fibrinogenolytic protease is an important biological factor in Bacteroides infection.

Amino Acid Sequence↗
PubMed1995

Bioactivation of cysteine conjugates of 1-nitropyrene oxides by cysteine conjugate beta-lyase purified from Peptostreptococcus magnus.

To determine the role of cysteine conjugate beta-lyase (beta-lyase) in the metabolism of mutagenic nitropolycyclic aromatic hydrocarbons, we determined the effect of beta-lyase on the mutagenicities and DNA binding of cysteine conjugates of 4,5-epoxy-4,5-dihydro-1-nitropyrene (1-NP 4,5-oxide) and 9,10-epoxy-9,10-dihydro-1-nitropyrene (1-NP 9,10-oxide), which are detoxified metabolites of the mutagenic compound 1-nitropyrene. We purified beta-lyase from Peptostreptococcus magnus GAI0663, since P. magnus is one of the constituents of the intestinal microflora and exhibits high levels of degrading activity with cysteine conjugates of 1-nitropyrene oxides (1-NP oxide-Cys). The activity of purified beta-lyase was optimal at pH 7.5 to 8.0, was completely inhibited by aminooxyacetic acid and hydroxylamine, and was eliminated by heating the enzyme at 55 degrees C for 5 min. The molecular weight of beta-lyase was 150,000, as determined by fast protein liquid chromatography. S-Arylcysteine conjugates were good substrates for this enzyme. As determined by the Salmonella mutagenicity test, 5 ng of beta-lyase protein increased the mutagenicity of the cysteine conjugate of 1-NP 9,10-oxide (10 nmol per plate) 4.5-fold in Salmonella typhimurium TA98 and 4.1-fold in strain TA100. However, beta-lyase had little effect on the cysteine conjugate of 1-NP 4,5-oxide (10 nmol per plate). Both conjugates exhibited only low levels of mutagenicity with nitroreductase-deficient strain TA98NR. In vitro binding of 1-NP oxide-Cys to calf thymus DNA was increased by adding purified beta-lyase or xanthine oxidase.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

[Multicentricity and concomitant tumors in renal cell carcinoma: analysis by serial section of resected kidneys].

Nephron-sparing surgery was initially limited to the patients with localized renal cancer (RCC) present bilaterally or in a solitary kidney. Recently there is controversy in the indication for partial nephrectomy or enucleation to incidentally defined small RCC with normal opposite kidney. We examined the incidence of multicentricity in 43 kidneys removed for RCC with a diameter of less than 80 mm. The mean diameter of the predominant tumors was 45 mm (range 12 to 80 mm). The kidneys were serially sectioned at 5 mm intervals. Three of 43 kidneys (7%) had multiple RCC. The size of the concomitant tumors ranged from 2 to 15 mm. The multicentricity had no relation to pathological grade, stage, vascular invasion or infiltration pattern. In addition, the other 4 kidneys had 2 adenomas, 1 angiomyolipoma and 1 fibroma. Therefore we observed a 16% incidence of small renal nodules and a 7% multicentricity of RCC in the nephrectomized kidneys with normal opposite kidney.

Adenoma↗
PubMed1995

Preoperative endocrine therapy in patients with locally advanced prostate cancer.

Recently, there has been increased interest in the application of preoperative endocrine therapy prior to radical prostatectomy for locally advanced cancer in order to enhance surgical curability and increase survival. Between 1986 and 1993, 40 patients with prostate cancer were given endocrine therapy before radical prostatectomy. Fifteen patients had stage B2 disease and 25 stage C. The median duration of preoperative endocrine therapy was 3.8 months, and all the patients subsequently underwent radical prostatectomy, pelvic lymphadenectomy and castration. There was an average 25.5% (0-71.8%) decreases in the maximal cross-sectional area of the prostate gland as determined by transrectal ultrasonography. Twenty-four of 25 patients with elevated levels of serum prostate-specific antigen (PSA) showed normal values after preoperative endocrine therapy. Evaluation of treatment-related histological effects, divided into three grades, revealed that 17 patients had pronounced, 11 moderate and 12 poor or no regression. Thirteen of the 40 patients (33%) demonstrated pathological downstaging of disease status from the diagnosis made at the initial clinical examination. After a median follow-up period of 36 months (3-100 months), 36 of the 40 patients are disease-free; two died of cancer 43 and 50 months after surgery, respectively. These results suggest that preoperative endocrine therapy may play an important role in the management of locally advanced prostatic cancer.

Adenocarcinoma↗
PubMed1995

[The antiemetic effect, safety and usefulness of tropisetron capsule in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin].

The antiemetic effect, safety and usefulness of once daily administration of tropisetron 5 mg capsule for 3 to 5 consecutive days was investigated in 37 cases of 12 stations in total, suffering from nausea and vomiting induced by a lower multiple dose of cisplatin. The efficacy ratings assessed every 24 hours on day 1, 2, 3, 4 and 5 were 88.6%, 85.7%, 82.9%, 74.1% and 76.9%, respectively. The final efficacy rating was 82.9% (29/35 cases). Although no adverse event was observed, increases in GOT and GPT, whose cause and relation to the investigational drug were unknown, were noted in 2 cases. Cases rated as useful or better were 82.9% (29/35 cases) of the overall. The above results reveal that tropisetron 5 mg capsule is significantly effective and highly safe in the treatment of nausea and vomiting induced by lower multiple dose of cisplatin. Tropisetron 5 mg capsule is thus deemed extremely useful antiemetic drug.

Antiemetics↗
PubMed1995

[The metabolic mode of circulating parathyroid hormone].

The circulating immunoreactive parathyroid hormone (PTH) exists in more than one form in plasma. These immunoreactive forms of PTH consists of intact hormone (large molecular weights) and lower molecular weight hormonal fragments from both the carboxyterminal and aminoterminal portions of PTH molecules. The most of the secreted intact PTH is cleaved or degraded in kidney and liver with forming C-terminal PTH. A little amounts of PTH are metabolized in bone or in other tissues bearing PTH/PTHrP receptor. This chapter reviews the mode of PTH metabolism in the peripheral tissues.

Animals↗
PubMed1995

Reactivities of mouse monoclonal antibody K2.7 to renal cancers in complement dependent cytotoxicity and antibody dependent cell-mediated cytotoxicity.

Immunohistochemical analysis by indirect immunoperoxidase staining demonstrated that monoclonal antibody (mAb) K2.7, derived from a mouse immunized with a renal cell carcinoma (RCC) cell line OS-RC-2, reacted with 89 of 95 renal cancer tissues (94%). Only 1 gastric and uterine cancer tissue showed positive staining among 87 cancer specimens from 9 different organs. Among normal human tissues, the renal tubule, testis, epithelium of the uterine endometrial gland and Fallopian tube, grey matter of cerebrum and cerebellum, and foreskin showed positive staining. Serological analysis by protein A mixed hemadsorption (PA) assay demonstrated that mAb K2.7 reacted with 25 of 31 RCC cell lines (81%), but with only 2 of 50 other cell lines from different organs. The specific antitumor activities of mAb K2.7 against RCC cell lines were investigated in vitro by complement dependent cytotoxicity (CDC) and antibody dependent cell-mediated cytotoxicity (ADCC) assays. In the CDC assay, all of the 9 RCC cell lines reactive serologically with mAb K2.7 were killed by mAb K2.7 with normal human serum, and the killing activity of mAb K2.7 correlated well with the reactivity of mAb K2.7 in the PA assay. mAb K2.7 showed the same killing activity against each of 3 RCC cell lines with sera from 9 patients with low and high stage renal cancers, as well as with normal human serum. In the ADCC assay, mAb K2.7 with peripheral blood leukocytes (PBLs) from 4 healthy donors showed cytotoxic activity against RCC cell lines. Peripheral blood leukocytes from the same 9 renal cancer patients also showed significant killing activity against the 3 RCC cell lines. These findings suggest the potential utility of mAb K2.7 for specific immunotherapy of renal cancer.

Animals↗