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Biomedical subjects

Y Kurata

Publications and source records attributed to Y Kurata.

At least 199 records · Page 11Linked to original sources

Promotion by L-ascorbic acid of urinary bladder carcinogenesis in rats under conditions of increased urinary K ion concentration and pH.

Dietary administration of 5% L-ascorbic acid plus 3% K2CO3 to male F344 rats clearly enhanced the development of preneoplastic and neoplastic lesions of the urinary bladder initiated with N-butyl-N-(4-hydroxybutyl)nitrosamine. Promotion of carcinogenesis by L-ascorbic acid and K2CO3 was associated with changes in urinary parameters: elevation of pH, increased K+ concentration, and increase in total ascorbic acid.

Animals↗

Determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry.

A method for the determination of isofloxythepin in biological fluids by gas chromatography-mass spectrometry is described. Isofloxythepin was readily converted into the trimethylsilyl ether by treatment with N,O-bis(trimethylsilyl)trifluoroacetamide. This derivative was separated on a 5% OV-101 column and determined, employing newly prepared isofloxythepin-d7 as an internal standard. Clean-up of isofloxythepin in blood and urine was efficiently achieved by back-extraction with hexane or hexane-toluene (9:1) under acidic and basic conditions, while isofloxythepin glucuronide in biological fluids was isolated by ion-exchange chromatography on Dowex 50W-X4 resin. The detection limit of isofloxythepin by this method was 50 pg. The blood and urine levels of isofloxythepin after oral administration of the drug to dogs were monitored by the proposed method.

Animals↗

Influences of strain and diet on the promoting effects of sodium L-ascorbate in two-stage urinary bladder carcinogenesis in rats.

The influences of strain and diet on the promoting effects of sodium L-ascorbate (SA) on two-stage urinary bladder carcinogenesis was investigated in male F344 and Lewis rats. Two kinds of commercial basal diets, Oriental MF and Clea CA-1, were used. Rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their drinking water for 4 weeks and then basal diet with 5% SA or without SA for 32 weeks. Treatment with SA increased the induction of neoplastic lesions of the urinary bladder in rats initiated by 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine. The promoting effect of SA for urinary bladder carcinogenesis was: F344 strain-Oriental MF diet greater than Lewis strain-Clea CA-1 diet greater than F344 strain-Clea CA-1 diet = Lewis stain-Oriental MF diet. In both strains or with both diets, SA-treatment increased the urinary pH and the concentrations of sodium ion and total ascorbic acid. These results demonstrate that strain and diet strongly influence susceptibility to the SA-promoting effects in rat urinary bladder carcinogenesis.

Animals↗

Inhibition of Ca2+ inward current in rabbit sinoatrial node by bunazosin, an alpha-adrenoceptor antagonist.

The electrophysiological effects of bunazosin, a novel alpha-adrenoceptor antagonist, were examined on isolated spontaneously beating sinoatrial node preparations of the rabbit by means of a double-microelectrode voltage clamp method. Bunazosin (above 10 microM) reduced the beating frequency, and the maximum rate of rise and the amplitude of action potentials. The slope of the diastolic depolarization (phase 4) was also decreased by the drug whereas the action potential duration at 50% repolarization was prolonged. Bunazosin decreased the slow inward current (Isi) and the time-dependent potassium outward current (IK). However, the major effect was the reduction of Isi. The results indicate that bunazosin, an alpha-adrenoceptor antagonist, depresses the action potential and automaticity of the sinoatrial node by inhibition of Ca channels.

Action Potentials↗

Combined chronic toxicity and carcinogenicity studies of morpholine oleic acid salt in B6C3F1 mice.

Morpholine oleic acid salt (MOAS) was administered to groups of 50 male and 50 female B6C3F1 mice in the drinking-water at levels of 0, 0.25 and 1.0%. Both sexes given 1.0% MOAS and females given 0.25% showed growth retardation. Significant increases in blood-urea nitrogen concentrations were only observed in the 1.0% male group. The incidence of squamous-cell hyperplasia of the forestomach epithelium was significantly higher in the males given 1.0% than in the controls. The male mice given 0.25% MOAS had a significantly reduced incidence of hepatocellular carcinoma in comparison with the control group and this trend was indicated also in the 1.0% group. This experiment did not demonstrate any carcinogenic effect of MOAS in mice at levels up to 1.0% in the drinking-water.

Animals↗

Absence of promotion potential for calcium L-ascorbate, L-ascorbic dipalmitate, L-ascorbic stearate and erythorbic acid on rat urinary bladder carcinogenesis.

The effects of treatment with calcium L-ascorbate, L-ascorbic dipalmitate, L-ascorbic stearate and erythorbic acid on two-stage urinary bladder carcinogenesis in F344 rats after initiation with N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) were examined. Carcinogen was administered at a dose of 0.05% in drinking water for 4 weeks and thereafter the test chemicals were given as a 5% supplement in the diet for the following 32 weeks. No increase in the induction of preneoplastic lesions, papillomas or carcinomas was apparent and it was concluded that none of the test chemicals possess promoting activity for urinary bladder carcinogenesis.

Animals↗

Dose-dependent effects of butylated hydroxyanisole, butylated hydroxytoluene and ethoxyquin for promotion of bladder carcinogenesis in N-butyl-N-(4-hydroxybutyl)nitrosamine-initiated, unilaterally ureter-ligated rats.

Dose-dependent effects of 3 antioxidants, butylated hydroxyanisole (BHA, 2.0, 1.0 and 0.5%), butylated hydroxytoluene (BHT, 1, 0.5 and 0.25%) and ethoxyquin (0.5, 0.25 and 0.125%) on the development of preneoplastic lesions in the bladder of N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)-treated rats were investigated. Feeding of the antioxidants after pretreatment of 0.05% BBN commenced and unilateral ureteric ligation was combined at week 3 of the experiment. Surviving rats were killed at the end of week 24. BHA and BHT, but not ethoxyquin increased dose-dependently the incidence and number of preneoplastic lesions, papillary or nodular hyperplasia of the urinary bladder in rats treated with BBN. Particularly, the incidence and number of PN hyperplasia in rats treated with 2.0% BHA and 1.0% BHT were significantly higher than those of the control group. Thus, promoting activities of BHA and BHT, but not ethoxyquin for the urinary bladder were confirmed in this system of BBN-initiated, unilaterally ureter-ligated rats.

Animals↗

13-week subchronic toxicity study with morpholine oleic acid salt administered to B6C3F1 mice.

The effect of subchronic administration of morpholine oleic acid salt (MOAS) was studied in B6C3F1 mice. The dose levels of MOAS used were 0%, 0.15%, 0.3%, 0.6%, 1.25%, and 2.5% in drinking water. Reduced weight gains were noted in both sexes in the 2.5% group as compared to controls, but reductions were not significant. Water consumption values showed a dose-related tendency for a decrease in both females and males. Urine analysis showed significant elevation of specific gravity in the males in the 0.6%, 1.25%, and 2.5% groups and the females in the 1.25% and 2.5% groups. Significant elevation of plasma urea nitrogen was observed in males of the 1.25% and 2.5% groups and in females of the 0.6%, 1.25%, and 2.5% groups. The relative weight of the kidneys showed a dose-dependent increase that was statistically significant for the 1.25% and 2.5% MOAS groups in both sexes. Except for cloudy swelling of the proximal tubules of the kidneys in mice on the 2.5% regimen, no treatment-related histopathological alterations were observed in organs of either sex.

Animals↗

Reciprocal modifying effects of isomeric forms of aminophenol on induction of neoplastic lesions in rat liver and kidney initiated by N-ethyl-N-hydroxyethylnitrosamine.

The effects of four isomeric forms of aminophenols, ortho-, meta-, para-aminophenol and acetaminophen (o-, m-, p-AP and AAP, respectively) on liver and kidney carcinogenesis initiated by N-ethyl-N-hydroxyethylnitrosamine (EHEN) were tested. Rats were given 0.1% EHEN (in their drinking water for 2 weeks) and then diet containing these compounds at concentrations of 0.8% for 49 weeks. Administration of o-AP and AAP significantly decreased the number and area of preneoplastic foci staining immunohistochemically for glutathione S-transferase placental type (GST-P) per unit area of liver section as compared with the values for rats given EHEN alone. o-AP and AAP also significantly decreased the incidence of hepatocellular carcinoma. In contrast, p-AP and AAP significantly increased quantitative values for kidney preneoplastic lesions and renal cell adenoma. It is suggested that the cytotoxic effects of these chemicals preferentially suppressed the proliferation of preneoplastic liver cells, but stimulated the mitotic activity of preneoplastic tubular lesions in the kidney.

Acetaminophen↗

Platelet glycoprotein IIb as a target antigen in two patients with chronic idiopathic thrombocytopenic purpura.

We have investigated the target antigens recognized by anti-platelet antibodies in patients with chronic idiopathic thrombocytopenic purpura (ITP) using an immunoblot procedure which could electrically separate the glycoprotein (GP) IIb/IIIa complex into GPIIb and GPIIIa. Various platelet proteins, having molecular weights of 167, 160, 145, 135, 124, 102, 92 and 80 kD, were recognized by circulating antibodies in 11 of 40 ITP patients. We identified the 145 kD antigen band, seen in two ITP patients, as GPIIb using thrombasthenic platelets as a source of target antigens. In one patient the anti-GPIIb antibody reacted with autologous GPIIb. These studies provide direct evidence for the presence of autoantibodies against GPIIb in some ITP patients.

Adult↗

Pancreatic vagal nerve is receptive to somatostatin in rats.

To investigate whether somatostatin, one of the pancreatic islet hormones, influences the afferent firing activity of the vagus innervating the pancreas and whether there is any relevant morphological basis for the electrophysiological event, cyclic somatostatin-14 was injected into the rat pancreatic artery. The somatostatin injection at a physiological (0.61 pmol) or a pharmacological (3.05 pmol) dose significantly increased the afferent firing discharge rate of the pancreatic vagus in rats anesthetized with urethan and chloralose. The present histological examination disclosed a glomuslike neurovascular body in the rat peripancreatic sinusoidal vein. The body included many small corpuscles, and the corpuscle contained a structure like the afferent nerve ending. The immunohistochemical study revealed that the structure preferentially bound exogenous somatostatin. These electrophysiological and histological findings suggest that the vagal pancreatic nerve is receptive to somatostatin and that there exists a local neural monitoring system for somatostatin secreted from the islets.

Afferent Pathways↗

[One-year chronic dietary toxicity study of d.d-T80-prallethrin in rats].

d.d-T80-prallethrin, a pyrethroid insecticide for sanitary use, was administered to Crj : CD (Sprague Dawley) rats at concentrations of 120, 600 or 3,000 ppm in diet for one year to assess the chronic toxicity potential and the reversibility. The summarized results obtained are as follows: 1. Chronic toxicity study 3,000 ppm : Decreases in body weight gain, food consumption, and water intake were observed. Slight alopecia in the neck and/or back was noticed during the first and second weeks, but the animals were recovered thereafter. Slight anemic changes such as decreases in hemoglobin concentration, hematocrit value, MCV and MCH were observed in the females at 52 week. Blood biochemistry revealed increases in total cholesterol (in the males and females at 13, 26 and 52 weeks), phospholipid (in the males and females at 13, 26 and 52 weeks), albumin (in the males at 13 and 26 weeks, in the females at 52 week), total protein (in the males at 26 week, in the females at 52 week), A/G ratio (in the males at 13 week, in the females at 26 week), creatinine (in the males at 52 week), urea nitrogen (in the females at 52 week), GOT (in the males and females at 52 week) and GPT (in the males and females at 52 week), and decreases in triglyceride (in the females at 26 and 52 weeks) and alkaline phosphatase (in the males at 13 and 52 weeks). In urinalysis, an increase in bilirubin was observed in the males at 52 week. Gross-pathology revealed a lower incidence of accentuated lobular pattern of liver (in the males at 26 week) and a higher incidence of enlarged liver (in the males at 52 week). In organ weight, increases in liver (in the males and females at 26 and 52 weeks), kidney (in the males at 26 and 52 weeks) and thyroid weights (in the males at 26 and 52 weeks, in the females at 26 week), and decreases in spleen (in the females at 26 and 52 weeks) and adrenal weights (in the females at 52 week) were observed. Histopathological examination revealed a lower incidence of fatty metamorphosis in the liver of females at 52 week. 600 ppm: An increase in liver weight was observed in the males at 26 week. 120 ppm: No effect was observed. 2. Reversibility study Almost all the above chronic toxicities were reversible.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

Increased circulating Ia-positive T cells in patients with idiopathic thrombocytopenic purpura.

Peripheral blood T cells from 40 patients with idiopathic thrombocytopenic purpura (ITP) were analysed for the presence of surface Ia antigens using monoclonal antibodies by indirect immunofluorescence. The percentage of Ia-positive (Ia+) T cells was significantly increased in patients with ITP (6.8 +/- 2.9%, P less than 0.005) as compared with normal controls (2.3 +/- 0.9%). There was an inverse correlation between the percentages of Ia+ T cells and platelet counts (r = 0.58, P less than 0.005) and a positive correlation between the percentage of these cells and platelet-associated IgG (PAIgG) values (r = 0.55, P less than 0.01). The percentage of Ia+ T cells was found to decrease within two weeks during therapy with high dose gamma-globulin or corticosteroid. We have previously reported the presence of T cells bearing both helper/inducer (H/I) and suppressor/cytotoxic (S/C) phenotypes (double labelled cells, DLC) in patients with ITP and an inverse correlation between the percentages of DLC and their platelet counts. In the present study, we showed that a major part of Ia+ T cells had both H/I and S/C phenotypes. We also examined the correlation between Ia+ T cells and autologous mixed lymphocyte reaction (AMLR). A defective AMLR was demonstrated in patients with ITP. Furthermore, an inverse correlation was found between the percentages of Ia+ T cells and the proliferative responses to AMLR (r = -0.49, P less than 0.01). These results suggest that increased circulating Ia+ T cells play a role in the abnormalities of the immunoregulatory system of ITP, especially in the regulation of autoantibody production.

Antibodies, Monoclonal↗

Catechol strongly enhances rat stomach carcinogenesis: a possible new environmental stomach carcinogen.

Catechol (CAS: 120-80-9) is present in the environment, being a major industrial chemical as well as a major phenolic component of cigarette smoke. Continuous oral treatment of rats with 0.8% catechol for 51 weeks after a single intragastric dose of 150 mg/kg of N-methyl-N'-nitro-N-nitrosoguanidine strongly enhanced both forestomach and glandular stomach carcinogenesis. In addition, and more importantly, catechol alone induced adenocarcinoma and adenomatous hyperplasia in the pyloric region of the glandular stomach. These results clearly indicate that this environmental contaminant merits classification as an enhancer of forestomach and glandular stomach carcinogenesis with complete carcinogenic potential for the glandular stomach. Its significance for gastric tumor development in man requires elucidation.

Adenocarcinoma↗

Analysis of antigen involved in circulating immune complexes in patients with idiopathic thrombocytopenic purpura.

Circulating immune complexes (CIC) were frequently observed in patients with idiopathic thrombocytopenic purpura (ITP). To analyse the pathogenic role of CIC, we studied the correlation between the disease activity and the CIC level, and whether platelet antigens were involved in CIC from ITP sera. Elevated CIC levels, measured by Clq, anti-C3 and spermatozoa micro-enzyme-linked immunosorbent assay, were found in 37%, 54% and 52% of the patients, respectively. However, there were no significant correlations (r = -0.11, -0.03 and -0.04, respectively) between the platelet count and the CIC level. Platelet antigens in CIC were detected with rabbit anti-human platelet serum. The CIC from 18%, 25% and 25%, respectively, of ITP sera contained platelet antigens, but the CIC from only 3%, 9% and 6% of SLE sera and from 3%, 2% and 5% of the sera of alloimmunized patients, respectively, contained these antigens. There were significant correlations (r = 0.51, 0.80 and 0.65, respectively) between the amount of platelet antigens and the CIC level in ITP sera. However, there were no correlations (r = -0.26, -0.29 and 0.08, respectively) between the platelet count and the amount of platelet antigens in the CIC. We detected platelet antigens in CIC from ITP sera, but surmise that these CIC perhaps do not play an important role in platelet destruction.

Antibody Specificity↗