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Biomedical subjects

O Wada

Publications and source records attributed to O Wada.

At least 91 records · Page 5Linked to original sources
PubMed1990

Inhibitory effects of carcinogenic tryptophan pyrolysis products on phytohemagglutinin-induced blast transformation of human lymphocytes.

In order to evaluate the effect of carcinogenic heterocyclic amines on the stimulus-reaction system of human cells, we examined the effect of 5 kinds of carcinogenic heterocyclic amines including 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), 2-amino-dipyrido[1,2-a:3',2'-d]imidazole (Glu-P-2), 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) on human lymphocyte (4 x 10(5) cells/ml) blast transformation induced by 0.125% phytohemagglutinin (PHA). Both Trp-P-1 and Trp-P-2 exhibited an inhibitory effect on the lymphocyte proliferation stimulated by PHA at the final concentration of 1.0-5.0 and 1.0-10 microM, respectively. The concentrations of Trp-P-1 and Trp-P-2 causing 50% inhibition were 3.1 and 5.1 microM, respectively. However, the other carcinogenic heterocyclic amines examined did not show any inhibitory effect on lymphocyte mitogenesis even at a final concentration of 10 microM. Viabilities of lymphocytes were more than 90% (n = 3 x 5) when 5 kinds of carcinogenic heterocyclic amines (0.1 ml) were respectively added at the final concentration of 10 microM to the lymphocyte culture medium (4 x 10(5) cells/0.9 ml).

Amines↗
PubMed1990

Detection of carcinogenic glutamic acid pyrolysis products in cigarette smoke condensate.

Carcinogenic glutamic acid pyrolysis products were measured in condensate of cigarette mainstream smoke by HPLC. These carcinogens were found to be present in all brands of filter-tipped cigarette analyzed. The mean levels of 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole and 2-aminodipyridol[1,2-a:3',2'-d]imidazole in the cigarette mainstream smoke were 0.66 and 0.63 ng/cig respectively.

Carcinogens↗
PubMed1990

[Pharmacokinetics of trace elements by noncompartmental analysis in rats (Part 1): Significance of the pharmacokinetic parameters].

Six-week-old male Wistar rats were administrated the radioisotopes of five trace elements (iron, zinc, copper, manganese and iodine) intravenously in order to elucidate the significance of their pharmacokinetics by noncompartmental analysis. The mean residence time (MRT) and variance of residence time (VRT) increased in the order Mn, Cu, I, Fe and Zn. Neither MRT nor VRT indicated any statistical significance between I and Fe. These results suggested that Mn and Cu were voided rapidly from the plasma, whereas Zn persisted in the plasma for the longest time among these elements. Though I and Fe showed quite different plasma disappearance curves, both were considered to diminish at almost the same speed. The volume of distribution at steady state (Vdss) increased in the order Cu (32 ml), Fe (62 ml), I (149 ml), Mn (185 ml) and Zn (1012 ml). The distribution coefficient (Kd) of these elements increased in the same order as Vdss did. For Cu and Fe, Vdss was intermediate between the plasma volume and total body fluid volume of the rat, while, for the others, Vdss was greater than the total body fluid volume. In particular, Vdss of Zn was the greatest among these elements. Hence, the present study suggested that the plasma concentrations of Cu and Fe may reflect their body contents fairy well, though those of I, Fe and Zn can hardly do so. Vdss and Kd are, therefore, considered to be useful as supplementary diagnostic indices to understand the plasma concentrations of trace elements. Systemic clearance (CLs) increased in the order Fe (0.02 ml/min), Zn (0.07 ml/min), I (0.21 ml/min), Cu (0.37 ml/min) and Mn (4.61 ml/min). The CLs of Mn was similar to the hepatic plasma flow rate of the rat in size, indicating that the Cls of Mn may be one of the greatest among trace elements. It appeared, therefore, that when administered intravenously, Mn may be transferred from the plasma to the tissues more easily than the other elements.

Animals↗
PubMed1990

Antagonism of gamma-aminobutyric acidA receptor-mediated responses by amino-gamma-carbolines.

The amino-gamma-carbolines 3-amino-1-methyl-5H-pyrido[4,3-b]indole and 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole were demonstrated to be potent convulsants. Administered i.p. in rats, these compounds penetrated the blood-brain barrier rapidly and appeared in the cerebrospinal fluid. When administered i.c.v., they induced convulsions with short onset latencies, suggesting that these compounds themselves have convulsant activities. In in vitro experiments using the whole cell clamp method, they suppressed gamma-aminobutyric acid (GABA)-induced Cl- current isolated on the dissociated mouse sensory neurons in dose-dependent manners through their actions as antagonists at GABAA receptors. The relative potency of the suppressive effects on GABA-induced Cl- current was compatible with that of the convulsant activities in mice. Furthermore, Ro15-1788 did not affect their convulsant activities. These results suggested that the amino-gamma-carbolines induced convulsions through their actions as antagonists at GABAA receptors and not through their actions as inverse agonists or antagonists at benzodiazepine receptors. Structure-activity relationships indicated that the 3-amino-group is important for the activities of amino-gamma-carbolines as GABAA receptor antagonists.

Animals↗
PubMed1990

[Ultrasonographic assessment of intravesical urine volume].

The assessment of intravesical urine volume is very important in the management of the patients with lower urinary tract obstruction or incontinence. As the non-invasive method for measuring residual urine volume, accuracy and usefulness of ultrasonographic measurement was evaluated in a total of 116 occasions in comparison with the conventional catheter technique. The values of the maximum transverse (W), cranio-caudal (H) and antero-posterior distance (D) of the inflated bladder were obtained by trans-abdominal scanning. These parameters were used for the ellipsoid formula (pi/6 x W x H x D). The ultrasonographic measurement of urine volume showed a high coefficiency against the conventional catheterized volume (r = 0.9543). Although a mean standard error was 56.3% of the actual volume, the amount of residual urine at the target of 50 ml and 100 ml could be accurately assessed by ultrasound with an accuracy of 90.5%. The method was also valid in follow-up study to monitor the changes of residual urine volume. The ultrasonographic assessment of intravesical urine volume is, thus, a non-invasive, useful tool in the management of the patients with voiding disturbance.

Evaluation Studies as Topic↗
PubMed1990

[A case control study of breast cancer, mammary cyst and dietary, drinking or smoking habit in Japan].

A matched pair analysis was done among patients with breast cancer, those with mammary cyst and those without any abnormality in mammary gland by ultrasonic echogram (U.S.) to investigate the relationship between dietary or smoking habit and mammary disease. Breast cancer was diagnosed pathologically, and mammary cyst by U.S.. 49 cancer-normal pairs and 36 cyst-normal pairs were obtained. Breast cancer had significant relationships with a large intake of bread (risk ratio (RR) = 1.60, 95% confidence interval (CI) = 1.03-2.49), margarine (RR = 2.17, CI = 1.20-3.49), cakes (RR = 1.83, CI = 1.18-2.84), soft drinks with sugar (RR = 8.00, CI = 1.33-48.29), meat (RR = 1.48, CI = 1.04-2.10) and a small intake of alcohol (RR = 0.20, CI = 0.06-0.63). Mammary cyst was significantly related with a large intake of fat (RR = 1.56, CI = 1.02-2.38). The result indicates that in Japan women with westernized dietary habit have a larger risk of breast cancer.

Adult↗
PubMed1989

Evidence that chromium is an essential factor for biological activity of low-molecular-weight, chromium-binding substance.

Biologically active Low-molecular-weight, chromium-binding substance (LMCr) has been isolated from the liver of rabbits injected with potassium bicarbonate and cow's milk. This substance enhances glucose oxidation and lipogenesis from glucose in rat adipocytes [Yamamoto A. et al. (1987) Eur. J. Biochem. 165, 627-631; (1988) J. Nut. 118, 39-45]. LMCr was shown to lose its activity almost completely as an effectant of glucose metabolism when Cr was deleted under acidic conditions and separated from LMCr by EDTA-chelation and successive molecular-sieve chromatography. Reincorporation of Cr3+ into apo-LMCr resulted in 50-90% recovery of its original activity. These findings suggest that the biological activity of LMCr resides in Cr.

Adipose Tissue↗
PubMed1989

Suppression of GABA-induced chloride current by 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2).

The effect of a convulsive agent, 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), on the GABA-induced chloride current (ICl) in dissociated mouse sensory neurons was investigated using the whole cell clamp method. Trp-P-2 reversibly suppressed the GABA-induced ICl in a dose-dependent manner. The IC50 for Trp-P-2 on the ICl evoked by 3 microM GABA was 11.1 microM. Ro15-1788 had no effect on the suppressive action of Trp-P-2. These results suggest that the observed effect of Trp-P-2 is mediated by its action as an antagonist at GABAA receptors.

Alanine↗
PubMed1989

Exposure level monitor of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole, a dietary carcinogen, in rabbits.

The present investigation describes a method for the detection of minute amounts of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1), a carcinogenic tryptophan pyrolysate, bound to the hemoglobin of erythrocytes and plasma from rabbits dosed orally with the dietary carcinogen. The method consists of the acid-induced release of the dietary carcinogen adducts as the free carcinogen and their extraction with methylene chloride and subsequent quantitation by high-performance liquid chromatography (HPLC). With this method, Trp-P-1 levels in plasma, platelets, and red blood cells were monitored for 12 weeks to determine a suitable indicator for estimating the exposure levels of the dietary carcinogen. The results suggest that Trp-P-1 in red blood cells that bound covalently to the hemoglobin is the most suitable for monitoring the long-term exposure levels.

Administration, Oral↗
PubMed1989

Exposure level monitor of a carcinogenic glutamic acid pyrolysis product in rabbits.

In order to determine a suitable indicator for estimating the exposure levels of the dietary carcinogen 2-amino-6-methyldipyrido[1,2-a:3',2'-d]imidazole (Glu-P-1), a carcinogenic glutamic acid pyrolysis product, the levels of Glu-P-1 bound to blood components were monitored for 8 weeks by a high-performance liquid chromatography method after the dietary carcinogen was administered as single oral doses (0.2-50 mg) to rabbits. In all rabbits dosed with Glu-P-1, Glu-P-1 in erythrocytes was detectable even on day 42 after administration. Glu-P-1 in plasma disappeared faster than did Glu-P-1 in erythrocytes. Glu-P-1 levels in rabbit hemoglobin were linearly related to administered doses at all points of time investigated. The results suggest that Glu-P-1 covalently bound to hemoglobin is very suitable for monitoring long-term exposure levels.

Administration, Oral↗
PubMed1989

Carcinogenic tryptophan pyrolysis products in airborne particles and rain water.

This is the first report that carcinogenic tryptophan pyrolysis products are present in airborne particles and rain water. The airborne particles were collected from August 1988 through October 1988 at 4 locations in Japan. The amounts of 3-amino-1,4-dimethyl-5H-pyrido[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2) in the air were 0.23 +/- 0.17 pg/m3 air (mean +/- SD, n = 18) and 0.16 +/- 0.15 pg/m3 air (n = 18), respectively. Moreover, these carcinogens were detected in rain water. These results indicate that Trp-P-1 and Trp-P-2 are ubiquitous environmental components.

Air Pollutants↗
PubMed1989

Carcinogenic tryptophan pyrolysis products in human lens.

Mutagenic and carcinogenic tryptophan pyrolysis products, 3-amino-1,4-dimethyl-5H-pyrido-[4,3-b]indole (Trp-P-1) and 3-amino-1-methyl-5H-pyrido[4,3-b]indole (Trp-P-2), have been identified in human cataractous lenses, but not in young bovine lenses. The amounts of Trp-P-1 and Trp-P-2 in senile cataractous lenses were 156.34 +/- 35.63 fmol (mean +/- S.D., n = 10) and 128.27 +/- 40.45 fmol (n = 10), respectively, while those of Trp-P-1 and Trp-P-2 in diabetic cataractous lenses were 158.29 +/- 40.06 fmol (n = 10) and 150.34 +/- 23.77 fmol (n = 10), respectively. In both senile and diabetic cataractous lenses, the concentrations of Trp-P-1 and Trp-P-2 in the insoluble protein fraction (fmol mg-1 protein) were significantly higher than those in the water-soluble protein fraction. Moreover, proteinase-K treatment of lens protein before extraction with methylene chloride significantly increased the recoveries of Trp-P-1 and Trp-P-2. These results clearly indicate that carcinogenic tryptophan pyrolysis products, gamma-carboline derivatives, are present in human cataractous lenses and that these fluorescent carcinogens are significantly concentrated in the insoluble lens proteins.

Adult↗
PubMed1989

Significant increase of IQ-type heterocyclic amines, dietary carcinogens in the plasma of patients with uremia just before induction of hemodialysis treatment.

The concentrations of 2-amino-3-methylimidazo(4,5-f) quinoline (IQ) and 2-amino-3,8-dimethylimidazo(4,5-f)quinoxaline (MeIQx), a family of mutagenic and carcinogenic heterocyclic amines, in the plasma of normal subjects (10 cases), patients with uremia receiving maintenance hemodialysis treatment (9 cases) and patients with uremia just before induction of hemodialysis treatment (5 cases) were determined by a high-performance liquid chromatography method. The plasma levels of IQ and MeIQx in uremic patients just before induction of hemodialysis treatment were 12.6 +/- 4.1 nM (mean +/- S.D., n = 5) and 10.0 +/- 2.3 nM (n = 5), respectively. In patients with uremia receiving maintenance hemodialysis treatment, IQ and MeIQx were detected in 4 and 2 out of 9 cases, respectively and the levels of those in the plasma were 4.1 nM (n = 4) and 1.7 nM (n = 2), respectively. However, IQ and MeIQx could not be detected in all normal subjects. These results indicate that uremic patients just before induction of hemodialysis treatment are actually exposed to higher levels of the carcinogenic heterocyclic amines, as compared with normal subjects and uremic patients receiving maintenance hemodialysis treatment.

Adult↗
PubMed1989

The decomposition and aggregation of rat lens protein induced by selenite in vitro and in vivo.

A single subcutaneous injection of sodium selenite at the dose of 20 mumol/kg body weight induced bilateral nuclear cataracts in suckling rats. This selenite-induced cataract incidence can be increased by pretreating animals with a glutathione synthesis inhibitor. Sodium dodecyl sulfate polyacrylamide electrophoresis of urea-soluble proteins from selenite-induced cataractous lenses showed the appearance of high molecular weight aggregates and decomposed products of lens proteins. These products were found in association with the emergence of a 45 K band. Incubation of water-soluble lens proteins with selenite in vitro produced changes similar to those demonstrated in selenite-induced cataractous lenses. Furthermore, selenite induced the gradual development of opalescence and the oxidation of sulfhydryl in the lens protein solution. Therefore, we presume that the oxidation of lens protein sulfhydryl by selenite is associated with both aggregate formation and the decomposition of lens proteins, and that these changes may provide a partial explanation for the mechanism of selenite cataract.

Animals↗
PubMed1989

[Effects of lithium deficient diet on avoidance behavior].

To determine whether lithium deficiency has an effect on lever-press avoidance behavior, low lithium diets were given to mice and the effects of these diets on conditioned lever press avoidance response were compared with that of a commercial diet containing 110 ng Li/g diet. Three low-lithium diets were prepared in this experiment and the lithium contents of the diets were 6.6, 36.6 and 76.6 ng Li/g diet. The mice used in this experiment had been maintained on a practical diet and trained by Sidman's situation previously. After checking that the conditioned response was established, they were divided into four groups. Three groups of mice each were given one of the low lithium diets, indicated above, and these were assigned into the lithium-deficient groups. Some mice were given the practical diet and this group was used as controls. The avoidance behavior was analyzed by the method reported previously by the authors. After changing the diet to a low-lithium one, the avoidance behavior was significantly suppressed in lithium-deficient groups and this appeared to be proportional to the level of lithium deficiency in the diet. Furthermore, this suppression in the avoidance behavior was recovered by lithium supplementation in the same experimental diet. These findings suggest that low-lithium intake may suppress acquired avoidance behavior in mice.

Animals↗
PubMed1989

[Present and future of carcinogenic tryptophan pyrolysis products in the environment].

Food has been considered an important factor for the genesis of cancer in man, as important as cigarette smoking. Diet influences the incidence of human cancer in many ways, directly and indirectly. Various kinds of carcinogens such as polynuclear aromatic hydrocarbons, N-nitro compounds and mycotoxins have been reported to be present in various foods. During the last decade, a new series of heterocyclic amines has been isolated as potent mutagens and later shown to be potent carcinogens in animals. Among them, carcinogenic tryptophan pyrolysates have been investigated from various points of view and useful pieces of information about them have been collected. Now, it is a matter of urgency to evaluate the effects of these carcinogens on humans. From this aspect, this review describes the information about carcinogenic tryptophan pyrolysates which has been collected and also future problems, especially those the hygienist will have to solve.

Carbolines↗
PubMed1989

Effects of dietary pyrazinamide, tryptophan, or nicotinic acid and gamma-ray irradiation on levels of NAD and NADP in various organs of mice.

The effects of large amounts of tryptophan, pyrazinamide, or nicotinic acid in diets on the contents of total NAD (NAD + NADH) and NADP (NADP + NADPH) of various organs were investigated in mice with or without gamma-irradiation. Female C3H/HeN mice were fed one of the following 4 kinds of experimental diets for one week: 1) control diet (20% casein diet containing 3 mg niacin per 100g diet); 2) diet supplemented by 0.5% L-tryptophan (T-diet); 3) diet supplemented by 0.5% L-tryptophan (T-diet); 4) diet supplemented by 0.1% nicotinic acid (NA-diet). Half of the mice in each group were subsequently irradiated with 8 Gy of gamma-ray (60 Co) after 4 h of fasting. Then, the contents of total NAD and NADP in thymus, spleen, kidney, liver, and blood were determined in all animals. The results indicated that NAD content of spleen was higher in PT-group (21.5%) and NA-group (23.2%) than in that of control group. In thymus, however, NAD content of only the PT-group was significantly greater (13.1%) than control. NAD level of kidney was also significantly higher (32.6%) in PT-group. By gamma-irradiation, NAD contents of thymus and spleen of all groups tended to be decreased, but those of kidney and liver were not always reduced. In the latter two organs, significant NAD reduction was shown only in kidney of PT-group and in liver of PT- and NA-groups. Even after irradiation, NAD levels of spleen and thymus in PT- and NA-groups tended to be kept higher than those in irradiated control group.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗