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Biomedical subjects

O Wada

Publications and source records attributed to O Wada.

At least 73 records · Page 4Linked to original sources
PubMed1992

Occurrence of carcinogenic amino-alpha-carbolines in some environmental samples.

The carcinogenic amino-alpha-carbolines, 2-amino-9H-pyrido[2,3-b]indole and AalphaC, have been measured in airborne particles, rain water, soil and cigarette-smoke-polluted indoor air by high-performance liquid chromatography. These carcinogens were found in all kinds of environmental samples examined, although MeAalphaC was not detected in soil. Considering the present results, together with the previous findings that these carcinogens were present in foodstuffs, cigarette smoke and diesel-exhaust particles, amino-alpha-carbolines are likely to be ubiquitous environmental pollutants. Our data also support the hypothesis that amino-alpha-carbolines are formed through combustion of various materials such as food, grass and petroleum.

Journal Article↗
PubMed1992

Formation of PhIP in a mixture of creatinine, phenylalanine and sugar or aldehyde by aqueous heating.

A mixture of 100 mM creatinine and 100 mM L-phenylalanine was heated at 60 or 37 degrees C in the presence of sugar or aldehyde. A mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formed in the model system was determined by reversed-phase HPLC. Any sugars tested induced the formation of PhIP when heated at 60 degrees C, though PhIP was not detected in a mixture without sugar. Among the sugars tested, D-erythrose and D-glyceraldehyde were more productive than pentose (D-arabinose and D-ribose) and hexose (D-glucose and D-galactose) in the yield of PhIP. Moreover, PhIP was formed even when a mixture of creatinine, L-phenylalanine and D-glucose or D-ribose was incubated at 37 degrees C for a long time. Both formaldehyde and acetaldehyde also induced the formation of PhIP, though PhIP was not detected in a mixture without sugar or aldehyde even when heated at 100 degrees C. These results indicate that PhIP can be formed at low-temperature heating and that either sugar or aldehyde is essential for PhIP formation in the model system. Our data also suggest that aldehydes may be a key reactant in the formation of PhIP in aqueous heating of the mixture of creatinine and L-phenylalanine.

Acetaldehyde↗
PubMed1992

Dobutamine improves afterload-induced deterioration of mechanical efficiency toward maximal.

We studied the effect of increased afterload on the ratios of O2 consumption (VO2) to external work (EW), VO2 to the systolic pressure-volume area (PVA), and PVA to EW at control state and with dobutamine in the left ventricles of open-chest dogs. Left ventricular volume was measured with a volumetric conductance catheter and coronary flow with an electromagnetic flowmeter. Hexamethonium bromide and atropine sulfate were administered before changes in end-systolic pressure (Pes) with an infusion of nitroprusside or angiotensin II. Dobutamine enhanced ventricular end-systolic elastance by 100%. In the control, with increases in Pes, EW/VO2 remained unchanged, PVA/VO2 increased by 48%, and EW/PVA decreased by 26%. Dobutamine increased both EW/VO2 and EW/PVA at any given Pes but decreased PVA/VO2. During dobutamine, EW/VO2 increased significantly with increases in Pes. The ratio of measured EW/VO2 to the theoretically predicted maximal EW/VO2 value for a given end-diastolic volume and contractility was 0.83 at a Pes of 70 mmHg, and this ratio decreased by 33% with increases in Pes in the control. During dobutamine, measured EW/VO2 values were almost equal to each corresponding theoretical maximal value, and the average decrease in the ratio with increases in Pes was 7%. Thus the enhanced inotropic state by dobutamine can restore the afterload-induced deterioration of EW/VO2 toward the normal maximal level.

Animals↗
PubMed1992

New redistribution index of nutritive blood flow to skeletal muscle during dynamic exercise.

BACKGROUND: Cardiac output is effectively redistributed to working muscle by regional changes in vascular resistance. However, there has been no suitable method to quantify blood flow distribution to large working and nonworking muscles involved in ergometer or treadmill exercise. METHODS AND RESULTS: To quantify the redistribution of blood flow, we compared thallium activity in a bicycle pedaling leg with that in the contralateral resting leg in 10 normal subjects. The regional thallium activity was expressed as a percentage of the whole-body radioisotope activity. Comparison of thallium activity between legs was performed at rest and at the work rates of anaerobic threshold and peak exercise during one-leg exercise. Thallium distribution of both legs was essentially the same at rest. At the anaerobic threshold, thallium activity increased about threefold to fourfold in the exercising thigh and about twofold in the exercising calf. The thallium distribution in these muscles at peak exercise was the same as at the anaerobic threshold. In the nonexercising calf, thallium distribution during exercise decreased significantly, and it was unchanged in the nonexercising thigh. Consequently, the ratio of thallium activity between the exercising and nonexercising thighs increased from 1.1 +/- 0.1 to 4.0 +/- 0.9 at the anaerobic threshold and to 3.3 +/- 0.6 at peak exercise. Similarly, the ratio between the exercising and nonexercising calves increased from 1.0 +/- 0.0 to 3.8 +/- 1.3 at the anaerobic threshold and to 3.5 +/- 1.0 at peak exercise. The ratios at peak exercise, however, did not differ significantly from those at the anaerobic threshold. CONCLUSIONS: These findings suggest that the redistribution of blood flow occurs predominantly during mild to moderate exercise; therefore, blood flow in the leg during strenuous exercise would depend primarily upon an increased cardiac output. Thus, the thallium activity ratio of exercising and nonexercising legs reflects the difference in vascular tone of each leg and could provide a noninvasive and quantitative index of blood flow redistribution.

Adult↗
PubMed1992

Inhibitory effects of organotin compounds on histamine release from rat serosal mast cells.

Tributyltin inhibited compound 48/80-induced histamine release from rat serosal mast cells in a dose-related manner. Triphenyltin and tripropyltin also showed a strong inhibitory effect on the histamine release and the degree of the inhibition was the same as that of tributyltin. The inhibitory effects of other organometals were much smaller than those of the organotins. Tributyltin and triphenyltin also showed a tendency to inhibit histamine release induced by concanavalin A + phosphatidylserine and calcium ionophore A 23187. The present results suggest that certain triorganotin compounds may have a specific inhibitory effect on histamine release by acting on the same process in each of the three stimulus responses.

Animals↗
PubMed1992

[Esophago-bronchial fistula caused by chemotherapy with bronchial artery infusion for pulmonary metastases from urinary tract cancer].

We treated a patient who had had postchemotherapeutic pulmonary metastases from urinary tract cancer by bronchial artery infusion (BAI) chemotherapy. Pulmonary lesions showed a 33.0% reduction after the treatment. However, esophago-bronchial fistula (EBF) occurred after the second BAI. The patient died of recurrent aspiration pneumonia and sepsis in the sequelae of the repair surgery. The fistula was considered to have resulted from an increase in the blood flow to the esophageal branch originating from the bronchial artery after the first BAI, which had consequently damaged the local tissue due to accumulation of anti-cancer drugs. In order to avoid these complications, the secondary change of blood flow should be examined precisely by preceding angiographical mapping, and the concentration and the infusion speed of the cytotoxic drugs, should be under adequate control.

Adult↗
PubMed1992

Elevation of levels of carcinogenic tryptophan pyrolysis products in plasma and red blood cells of patients with uremia.

The 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 measured in plasma and red blood cells (RBC) of patients with uremia and normal subjects by using a high-performance liquid chromatography (HPLC) method. In both uremic patients and normal subjects, these carcinogens have been detected in RBC as well as plasma. Trp-P-1 and Trp-P-2 levels in plasma of uremic patients were significantly higher than those of normal subjects. Moreover, these carcinogen levels in RBC (per hemoglobin) were significantly elevated in uremic patients in spite of the presence of severe anemia. These results suggest that patients with uremia are continuously exposed to higher levels of these carcinogens as compared with normal subjects. Our data also support the idea that these carcinogens in plasma and RBC are suitable for monitoring exposure levels in humans.

Adult↗
PubMed1992

Characterization of G-proteins in rat glomeruli.

G-proteins in rat glomeruli were examined using bacterial toxin-catalyzed ADP-ribosylation and specific immunoblots. ADP-ribosylation catalyzed by cholera and pertussis toxin demonstrated the existence of Gs and Gi proteins in the glomerular membranes. Immunoblots further revealed two types of Gs alpha (45 and 52 kDa), Gi alpha 1 and/or Gi alpha 2 (40-41 kDa), Gi alpha 3 (40 kDa) and G beta (35-36 kDa) but not Go alpha in the membranes of the glomeruli. The predominant subspecies of Gs alpha was a 52 kDa protein. However, detectable amounts of G-proteins did not exist in cytosolic extracts of the glomeruli. We conclude that several subspecies of Gs and Gi proteins are present in rat glomerular membranes.

Adenosine Diphosphate↗
PubMed1991

Quality control program on biological monitoring by Japan Federation of Occupational Health Organizations.

Since 1980, the Japan Federation of Occupational Health Organizations has been conducting an external quality control survey for biological monitoring under a contract with the Ministry of Labour of the Japanese Government. The number of participating organizations has increased from 91 in 1980 to 179 in 1987. The items in the program were lead and free erythrocyte protoporphyrin concentrations in blood, and lead, coproporphyrin, delta-aminolevulinic acid, chromium, hippuric acid, methylhippuric acid, total trichloro-compounds, mandelic acid, and phenol concentrations in urine. Evaluation was based on a scoring system. The scores were on the slope of major axis for probable ellipse, the slope of regression line, square root of error mean square for regression, performance indices, and the difference between 'true' and observed values of each sample. There was a gradual improvement in the evaluation scores as a function of time. The improvement was paralleled by the adoption of modern analytical methods such as flameless atomic absorption spectrometry for blood-lead measurement and high-performance liquid chromatography for urinary hippuric acid determination in many participants. These methods are simple in operation and reliable in performance. It was considered very probable that the program promoted the adoption.

Environmental Monitoring↗
PubMed1991

Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction.

The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

Collateral Circulation↗
PubMed1991

Detection of carcinogenic amino-alpha-carbolines and amino-gamma-carbolines in diesel-exhaust particles.

Diesel-exhaust particles are known to contain mutagenic and carcinogenic chemicals. The aim of this study was to determine whether carcinogenic amino-alpha-carbolines and amino-gamma-carbolines are present in diesel-exhaust particles. These carcinogens which were originally isolated from pyrolysates of proteins and amino acids have been detected in diesel-exhaust particles obtained from two test vehicles as well as in standard materials of automobile-exhaust particles obtained from National Institute for Environmental studies. The levels of these carcinogens were far less than those of polycyclic aromatic hydrocarbons such as benzo[a]pyrene. However, the presence of these amino-alpha-carbolines and amino-gamma-carbolines in diesel-exhaust particles suggests that these compounds are environmental pollutants and also that diesel-exhaust is one of the sources of these carcinogens in the outdoor environment.

Journal Article↗
PubMed1991

Urinary excretion levels of carcinogenic glutamic acid pyrolysis products and their N-acetyl derivatives in humans.

UNLABELLED: The carcinogenic glutamic acid pyrolysis products 2-amino-6-methyldipyrido [1, 2-a: 3', 2'-d]imidazole (Glu-P-1) and 2-amino-dipyrido [1, 2-a: 3', 2'-d] imidazole (Glu-P-2), and their N-acetyl derivatives were measured in 24-h urine of individual subjects by high-performance liquid chromatography. These compounds were detected in all urine samples analyzed, although the contents varied widely among subjects. The mean levels of Glu-P-1, N-acetyl-Glu-P-1, Glu-P-2 and N-acetyl-Glu-P-2 in 24-h urine were 0.53, 0.41, 2.12 and 4.60 pmol, respectively. In vitro experiments revealed N-acetyltransferase activity with Glu-P-1 and Glu-P-2 in the cytosolic fractions from rat kidneys and human autopsy kidney specimens as well as those from liver specimens, suggesting that extrahepatic tissues may also play significant roles in the N-acetylation of these carcinogens. These results show that Glu-P-1 and Glu-P-2, after being partially N-acetylated in metabolic organs such as liver and kidney, are excreted into urine together with their N-acetyl derivatives. It is suggested that daily excretion of carcinogenic glutamic acid pyrolysis products and their N-acetyl derivatives into urine can be a suitable biological monitor for exposure to these carcinogens. ABBREVIATIONS: Glu-P-1, 2-amino-6-methyldipyrido [1, 2-a: 3', 2'-d] imidazole; Glu-P-2, 2-aminodipyrido [1, 2-a: 3', 2'-d] imidazole; N-acetyl-Glu-P-1, 2-acetylamino-6-methyldipyrido [1, 2-a: 3', 2'-d] imidazole; N-acetyl-Glu-P-2, 2-acetylaminodipyrido[1,2- a:3', 2'-d]imidazole; HPLC, high-performance liquid chromatography.

Acetylation↗
PubMed1991

Carcinogenic tryptophan pyrolysis products in the environment.

The purpose of this study is to evaluate the risk of carcinogenic tryptophan pyrolysis products to human health. During the last decade, a new series of heterocyclic amines has been isolated as potent mutagens and later shown to be potent carcinogens in experimental animals. Among them, 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), carcinogenic tryptophan pyrolysis products, have been investigated from various points of view and useful pieces of information about them have been collected. These carcinogens are widely distributed in the environment such as airborne particles, rain water, cigarette smoke and cooked foods, and they possess various pharmacotoxicological activities such as convulsant activities and potent inhibitory effects on platelet function and dopamine metabolism. Recent investigations revealed that these compounds are present in human samples such as plasma, urine and bile, indicating that humans are actually exposed to these compound. It is a matter of urgency to establish a suitable method for monitoring the exposure levels of these compounds to humans.

Animals↗
PubMed1990

Simultaneous determination of amino-alpha-carbolines and amino-gamma-carbolines in cigarette smoke condensate by high-performance liquid chromatography.

A method for the simultaneous detection of amino-alpha-carbolines (2-amino-alpha-carboline and 2-amino-3-methyl-alpha-carboline) and amino-gamma-carbolines (3-amino-1,4-dimethyl-5H-pyrido [4,3-b]indole and 3-amino-1-methyl-5H-pyrido [4,3-b]indole) by high-performance liquid chromatography has been developed. It consists of a three-step purification using three different columns with fluorometric detection. With this method, we have demonstrated that both amino-alpha-carbolines and amino-gamma-carbolines are present in cigarette smoke condensate. The method may be useful for detecting these carcinogens in various materials.

Carbolines↗
PubMed1990

Identification of carcinogenic tryptophan pyrolysis products in human bile by high-performance liquid chromatography.

The 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 demonstrated to be present in human bile through use of a high-performance liquid chromatography (HPLC) method. The method consists of the acid-induced release of the carcinogens from bile components and their extraction with methylene chloride and subsequent quantification by HPLC. In seven subjects who had received catheterization of the bile duct and external biliarydrainage, the average amounts of Trp-P-1 and Trp-P-2 excreted daily in the bile were 408 fmol/day (n = 7) and 864 fmol/day (n = 7), respectively. In one subject, furthermore, significant daily changes of these carcinogen levels in bile and plasma were confirmed during 2 weeks of observation. These results indicate that one of the excretory pathways of these carcinogens is via bile. Our data also may suggest that Trp-P-1 and Trp-P-2 are derived from everyday foods.

Bile↗
PubMed1990

Monoclonal antibody to 2-amino-3-methylimidazo(4,5-f)quinoline, a dietary carcinogen.

In order to investigate relationships between human carcinogenesis and dietary carcinogens, one hybridoma cell line secreting a monoclonal antibody against 2-amino-3-methylimidazo(4,5-f)quinoline (IQ), a dietary carcinogen, was produced by fusing splenocytes from Balb/c mice immunized with IQ-Lysine(Lys)-Ascaris protein conjugate. The subclass of monoclonal anti-IQ antibody was determined by double immunodiffusion using culture medium and identified as IgG1. Monoclonal anti-IQ antibody was purified from ascites fluids of Balb/c mice with affinity chromatography on Protein A-Sepharose CL4B and analyzed concerning its cross-reactivity and sensitivity with RIA. Finally, we showed that our monoclonal antibody recognized IQ, 2-amino-3,4-dimethylimidazo(4,5-f)quinoline (MeIQ) and several beta-carbolines more intensely and that the sensitivity to IQ was 23 nmol in 50% displacement.

Animals↗
PubMed1990

Carcinogenic tryptophan pyrolysis products in cigarette smoke condensate and cigarette smoke-polluted indoor air.

The 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 measured in condensate of cigarette mainstream smoke by high-performance liquid chromatography. These carcinogens have been detected in indoor air as well as in the air of the outdoor environment. Levels of these carcinogens in indoor air were much higher than those in outdoor air. The source of these carcinogens in indoor air was determined to be cigarette smoke by the application of smoking machine studies. Concentrations of these carcinogens in indoor air increased markedly with an increase in cigarettes smoked. The results in this investigation suggest that cigarette smoking is a source of carcinogenic tryptophan pyrolysis products in the indoor environment. Our data also suggest that smokers are persistently exposed to the carcinogenic heterocyclic amines together with potent carcinogens such as polynuclear aromatic hydrocarbons and N-nitroso compounds.

Journal Article↗