Hydroxyl free radical (.OH) formation reflected by salicylate hydroxylation and neuromelanin. In vivo markers for oxidant injury of nigral neurons.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
H Miyake
Publications and source records attributed to H Miyake.
[CT findings of pulmonary paragonimiasis westermani].
The CT findings of six patients (three symptomatic and three asymptomatic) with pulmonary paragonimiasis westermani were reviewed in correlation with the findings of radiography. Pleural changes were recognized in all cases on CT. In addition to pleural fluid collection and hydropneumothorax, which were demonstrated on plain radiograph, CT showed minimal pleural thickening and adhesion adjacent to the parenchymal lesions. CT showed round nodules of lower attenuation within a subpleural consolidation of triangular shape in two patients. Small air-filled cavities in a parenchymal lesion with central dense spots were demonstrated in two patients, and multiple cavities with irregular wall were seen in one patient. CT also demonstrated the parenchymal lesion with a tunnel-like cavity in one patient. These may represent the worm nodules, the worm within worm cysts, and the worm migration tract, respectively. These pulmonary lesions were located adjacent to the localized pleural thickening or adhesion in all six cases. CT was more useful than radiography in the diagnosis of pulmonary paragonimiasis westermani.
Adolescent↗
Effects of an NK1 receptor antagonist, FK888, on constriction and plasma extravasation induced in guinea pig airway by neurokinins and capsaicin.
The effects of FK888, an NK1 receptor antagonist, on airway constriction and airway plasma extravasation induced by neurokinins and capsaicin were investigated in guinea pigs. FK888 inhibited substance P (10(-8) M)- and neurokinin A (10(-9) M)-induced contraction of isolated guinea pig trachea, with IC50 values of 3.2 x 10(-8) and 4.2 x 10(-6) M, respectively. FK888 given i.v. inhibited substance P (13.5 micrograms kg-1)-induced airway constriction with an ED50 value of 0.40 mg kg-1 but did not inhibit neurokinin A (1.1 micrograms kg-1)- and capsaicin (3.1 micrograms kg-1)-induced airway constriction at a dose of 1 mg kg-1. On the other hand, FK888 given i.v. inhibited airway plasma extravasation induced by substance P (1.3 micrograms kg-1), neurokinin A (11 micrograms kg-1) and capsaicin (100 micrograms kg-1) with equal potency and ED50 values of 0.011, 0.0063 and 0.019 mg kg-1, respectively. When FK888 was given locally (into the airway directly) inhibitory activities were more potent than following i.v. administration. In this case FK888 inhibited substance P-, neurokinin A- and capsaicin-induced airway constriction with ED50 values of 3.2, 190 and 550 micrograms kg-1, respectively, suggesting that an about 100 times higher dose is required to inhibit neurokinin A- and capsaicin-induced airway constriction than substance P-induced constriction. FK888 given orally was also effective in substance P-, neurokinin A- and capsaicin-induced airway plasma extravasation with ED50 values of 4.2, 5.9 and 9.5 mg kg-1.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Effects of nitric oxide synthase inhibitors on duodenal alkaline secretion in anesthetized rats.
We examined the effects of NG-nitro-L-arginine methyl ester (L-NAME), the nitric oxide (NO) synthase inhibitor, on duodenal HCO3- secretion in anesthetized rats. L-NAME (1-5 mg/kg i.v.), given as a single injection, increased HCO3- secretion in a dose-dependent manner. This effect of L-NAME was mimicked by NG-monomethyl-L-arginine (50 mg/kg i.v.) and was significantly antagonized by the simultaneous administration of L-arginine (200 mg/kg i.v.) but not D-arginine. The increased HCO3- response to L-NAME was also significantly reduced in vagotomized animals. These findings suggest that the inhibition of NO biosynthesis leads to an increase of duodenal HCO3- secretion, partly mediated by the vagus nerves.
Amino Acid Oxidoreductases↗
Neurobehavioral effects of chronic occupational exposure to organic solvents among Japanese industrial painters.
To investigate the relationship between chronic exposure to organic solvents and changes in central nervous system function, industrial painters were compared with an age- and education-matched referent group of nonexposed workers. Eighty-one male painters completed a symptom questionnaire. Twenty painters underwent both questionnaire and neuropsychological examinations. From the results of pairwise comparisons of the symptoms, dry and scaly skin, being easily depressed without reason, coldness of hands and legs, being easily irritated without reason, loss of appetite, dizziness, and unsteadiness occurred statistically significantly more often among the exposed subjects than among the referents. Performances on the Digit symbol test and vocabulary test scores (synonyms) in exposed subjects were significantly lower than those of controls. In multiple regression models, controlling for age, education, and alcohol intake, a significant relation was found between the duration of the solvent exposure and poor performance in both the Block design and Digit span tests. The relation between toluene exposure and poor performance in both the Santa Ana coordination test and the Benton visual retention test was also significant. The results suggest that a symptom inquiry and some behavioral tests are helpful for detecting the possible effects of exposure to low levels of organic solvents. However, no consistent pattern was observed in regard to the effects of organic solvent exposure on neurobehavioral function, which is coincident with the type I toxic central nervous system disorder as classified by the World Health Organization.
Adult↗
Acute neurobehavioral effects of co-inhalation of toluene and n-hexane on schedule-controlled behavior in rats.
Whether coexposure to toluene and n-hexane had any combined effects on the shock avoidance performance in rats was studied. Eighteen Wistar male rats with an avoidance rate of over 80% were selected and divided to three groups based on performance and body weight: (1) toluene, (2) n-hexane, and (3) toluene + n-hexane. Each group was exposed alternately first to air and then to a particular organic solvent for 4 hr at various concentrations (50, 100, 200, 400, or 800 ppm, in ascending order). The effects of each organic solvent were evaluated by comparing the performance of rats during and after exposure with their own performance under the sham exposure to air by three-way ANOVA. The main results were that (1) 200, 400, or 800 ppm toluene exposures increased lever press rates, (2) 50 ppm n-hexane exposure decreased lever press and avoidance rates in a transitory manner and 800 ppm n-hexane exposure increased the lever press rate, (3) the 50 ppm mixture (25 ppm toluene + 25 ppm n-hexane) decreased lever press and avoidance rates persistently during and after the 4-hr exposure and the 800 ppm mixture (400 ppm toluene + 400 ppm n-hexane) decreased lever press and avoidance rates unpredictably when compared to the results of 400 or 800 ppm of toluene or n-hexane alone. In conclusion, n-hexane showed narcotic effects at 800 ppm and modified the acute neurobehavioral effects of toluene in rats at 400 ppm toward unpredictable results.
Administration, Inhalation↗
Immunohistochemical localization of superoxide dismutase in congenital hydrocephalic rat brain.
The effects of active oxygen species in the development of congenital hydrocephalus have been investigated. Superoxide dismutase (SOD) is one of the scavengers of active oxygen species and there have been many recent reports on the relationship between neurological disorders by active oxygen species following reperfusion for ischemic brain and SOD. In this study, the localization of Cu-SOD and Zn-SOD in WIC-Hyd congenitally hydrocephalic rat brains was identified by the enzyme unlabeled antibody method. We examined the localization of SOD in the choroid plexus, hippocampus, and ependymal cells of the lateral ventricle and aqueduct of WIC-Hyd rats. SOD was hardly observed in the choroid plexus and faintly localized in the hippocampus and ependymal cells of the congenitally hydrocephalic brain, but was observed equally in the cytoplasm of the choroid plexus, hippocampus, and ependymal cells in control animals. In the hippocampus, less SOD was found in hydrocephalic rats than in controls. The SOD was slightly observed in the CA1 pyramidal cells in hydrocephalic rats. In the lateral ventricle and aqueductal ependyma, less SOD was found in hydrocephalic than in controls rats. The amount of Cu, Zn-SOD in the congenitally hydrocephalic rat brain was less than in the control, especially in the choroid plexus. Therefore, we suspect that the production of SOD is congenitally reduced in the congenitally hydrocephalic rat brain, and this may promote the impairment of the function of choroid plexus and cilia due to increased active oxygen species. The reduction of SOD in the choroid plexus, hippocampus and ependymal cells of ventricles or aqueduct may promote the development of hydrocephalus in the congenitally hydrocephalic rat.
Animals↗
Extrarenal Wilms' tumour.
Extrarenal Wilms' tumour is rare and its imaging has received scant mention in the literature. We describe a 2-year-old boy with a firm mass in the right flank. CT, MRI and ultrasonography showed an inhomogeneous solid mass located in the retroperitoneum, which was separate from the right kidney. Angiography showed an enlarged right gonadal artery and irregularly tortuous vessels in the tumour similar to intrarenal Wilms' tumour ("spider leg" or "creeping vine" appearance). Histopathological examination confirmed an extrarenal Wilms' tumour.
Child, Preschool↗
Incident angle dependence of proton response of CR-39 (TS-16) track detector.
The proton response of the TS-16 type of CR-39 plastic nuclear track detector has been studied with accelerated and fast neutron induced protons in vacuum and in air. The diameters of etched tracks were measured as a function of etching time and the etch rate ratio and the etch induction layer were determined from the growth curve of the diameter using a variable etch rate ratio model. In the case of the accelerated protons in vacuum an anomalous incident angle dependence of the response is observed.
Calibration↗
Cardiovascular profile of MPC-1304, a novel dihydropyridine calcium antagonist: comparison with other calcium antagonists.
The cardiovascular profile of a novel calcium antagonist, MPC-1304 and its active metabolites were investigated in experimental animals in vitro and in vivo, and were compared with those of other calcium antagonists or nitroglycerin (NTG). The ratio of negative chronotropic/negative inotropic effect of MPC-1304 was 23 times higher than that of nifedipine in paced left and spontaneously beating right atria of guinea pigs. MPC-1304 and nifedipine did not change atrial-His (AH) conduction time or His-ventricular (HV) conduction time at hypotensive doses in open-chest dogs, whereas diltiazem prolonged AH time. MPC-1304 increased coronary blood flow, and strongly decreased myocardial oxygen consumption (MVO2) by decreasing blood pressure (BP) and heart rate (HR) in open-chest dogs. Left ventricular pressure (LVP) was not changed. Contractile force (dp/dt) was slightly increased by its action on afterload. MPC-1304 and nifedipine did not dilate the large coronary artery, but NTG did. MPC-1304 increased blood flow of the peripheral arteries, especially vertebral and CBF in anesthetized dogs. Cerebral blood flow (CBF) also increased. MPC-1304 decreased serum cholesterol levels and the plaque area of the aorta in cholesterol-fed rabbits. Because of this cardiovascular profile, MPC-1304 should be useful in treatment of hypertension as well as angina pectoris.
Animals↗
Distribution of radioactivity from 14C-formaldehyde in pregnant mice and their fetuses.
The distribution of 14C after the administration of 14C-formaldehyde was studied in pregnant mice by a whole body low temperature autoradiographic technique. The concentrations of formaldehyde and its metabolites in maternal and fetal blood and tissues were determined in unsectioned tissues by liquid scintillation spectrophotometry. The binding of 14C from 14C-formaldehyde to cells and DNA in maternal and fetal mouse liver was also measured. Radioactivity of 14C deriving from 14C-formaldehyde was found immediately after injection, and showed strong accumulation and retention three hours after injection. The organs that had high concentrations at all studied survival intervals were maternal liver, intestinal mucosa, bone marrow, kidneys, and salivary glands. Considerable amounts of radioactivity were found in the fetuses at six hours after injection, and the concentrations were almost the same as in the maternal tissues. The elimination of 14C-formaldehyde and metabolites from the placenta and fetus occurred more slowly than from maternal tissue.
Animals↗
Circadian variations of acute toxicity and blood and brain concentrations of inhaled toluene in rats.
To investigate circadian variations in the acute toxicity of toluene, rats were exposed to it (2000 ppm or 4000 ppm) both in the dark (the animals' active phase) and the light (the inactive phase) for 4 hours. The performance decrements of rats were greater in the light phase than in the dark phase in all time zones of exposure to toluene. In the dark phase, the performance recovered almost to that pre-exposure, whereas a significant delay of recovery was noted in the light phase. The differences in the number of lever presses between exposure to 2000 ppm toluene and control (air) exposure were also greater in the light phase than in the dark phase. Significant differences according to the time of exposure were also found in toluene concentrations in blood and the brain. Both blood and brain concentrations in the light phase were higher than those in the dark phase at four hours after exposure to 2000 ppm toluene or at two hours after exposure to 4000 ppm toluene. These results suggest that there was a significant difference in circadian susceptibility after exposure to toluene, which might be caused by circadian differences in the pharmacokinetics of toluene in the light and dark phases.
Animals↗
Acute effects of trichloroethylene on blood concentrations and performance decrements in rats and their relevance to humans.
This study was designed to clarify the nature of effects of trichloroethylene (TCE) on the central nervous system, and to determine the critical concentrations in blood associated with specific behavioural changes. This was achieved by a follow up of the whole time course of TCE intoxication during and after exposure. The effects of a single four hour exposure to TCE on signalled bar press shock avoidance in rats were tested by methods previously applied to investigate the acute neurobehavioural effects of exposure to toluene. Even low exposure to TCE induced shock avoidance performance decrements in rats. Rats exposed to 250 ppm TCE showed a significant decrease both in the total number of lever presses and in avoidance responses at 140 minutes of exposure compared with controls. The rats did not recover their pre-exposure performance until 140 minutes after the exhaustion of TCE vapour. Exposures in the range 250 ppm to 2000 ppm TCE for four hours produced concentration related decreases in the avoidance response rate. No apparent acceleration of the reaction time was seen during exposure to 1000 or 2000 ppm TCE. The latency to a light signal was somewhat prolonged during the exposure to 2000 to 4000 ppm TCE. It is estimated that there was depression of the central nervous system with slight performance decrements and the corresponding blood concentration was 40 micrograms/ml during exposure. Depression of the central nervous system with anaesthetic performance decrements was produced by a blood TCE concentration of about 100 micrograms/ml. These results showed effects of TCE on the central nervous system that were considered to be a function of both the exposure concentration and the duration of exposure, which are closely related to the TCE concentration in blood.
Animals↗
A new point mutation in the deoxyribonucleic acid-binding domain of the vitamin D receptor in a kindred with hereditary 1,25-dihydroxyvitamin D-resistant rickets.
Hereditary 1,25-dihydroxyvitamin D [1,25-(OH)2D]-resistant rickets (HVDRR) is a rare disorder characterized by rickets, alopecia, hypocalcemia, secondary hyperparathyroidism, and normal or elevated serum 1,25-dihydroxyvitamin D levels. We describe a patient with typical clinical characteristics of HVDRR, except that elevated levels of serum phosphorus were present coincident with increased levels of serum intact PTH. The patient was treated with high dose calcium infusion after an ineffective treatment with 1 alpha-hydroxyvitamin D3; serum calcium and phosphorus as well as intact PTH and alkaline phosphatase levels were normalized. Evaluation of phytohemagglutinin-activated lymphocytes derived from this patient revealed that 1,25-(OH)2D3 was unable to inhibit thymidine incooperation, a result that contrasts with the capacity of 1,25-(OH)2D3 to inhibit uptake into normal activated lymphocytes. 1,25-(OH)2D3 did not induce human osteocalcin promoter activity after transfection of this DNA linked to a reporter gene into patient cells. Cointroduction of a human vitamin D receptor (VDR) cDNA expression vector with the reporter plasmid, however, restored the hormone response. Evaluation of extracts from the patient cells for VDR DNA binding revealed a defect in DNA binding. Analysis of genomic DNA from the patient's cells by PCR confirmed the presence of a point mutation in exon 2 of the VDR. This exon directs synthesis of a portion of the DNA-binding domain of the receptor. We conclude that the genetic basis for 1,25-(OH)2D3 resistance in this kindred with VDR-positive HVDRR is due to a single base mutation in the VDR that leads to production of a receptor unable to interact appropriately with DNA.
Binding Sites↗
[The state of the art of gastric antisecretory drugs].
This review article describes the effect and mechanism of various antisecretory drugs. Both histamine H2-receptor antagonists and gastric proton pump inhibitors are now world-widely used as the first choice for the treatment of acid-related diseases. Because of their potential effectiveness in inhibiting gastric acid secretion, new H2-antagonists and pump inhibitors are under development with the aim of mitigating of the side effects. The local antisecretory effects of FPL-52694, NC-1300-O-3 and ME 3407, which were demonstrated in Heidenhain pouch dogs, will provide clues for the development of new types of antisecretory drugs. Antigastrin drugs are also promising.
Animals↗
[Association of parents' occupational exposure to cancer in children. A case-control study of acute lymphoblastic leukemia].
The objectives of the present study were to evaluate the preconceptual, prenatal, and postnatal environmental factors as possible etiologic agents of childhood neoplasms. An exploratory case-control study was conducted on parents of children less than 15 yr of age with acute lymphocytic leukemia (ALL). Data were obtained on 147 identified cases by interview from their mothers and by mail questionnaire from their fathers. Hospital control cases were matched by sex and age, while population control cases were matched by place of residence, and sex. The following results were obtained. 1) As for the occupation of the parents, more fathers of the cases were engaged in occupations related to agriculture, medicine, and science than those of the controls, and more mothers of the cases were engaged in agriculture than those of the controls. 2) No significant relation could be demonstrated between ALL and occupations related to hydrocarbon and ionizing radiation. 3) The results of multivariate analysis showed that in comparison with the hospital control cases the preconceptual exposure to chemicals and the prenatal exposure to pesticides of the fathers and the prenatal exposure to benzine and spray pesticides of the mothers were risks of high significance. In comparison with population control cases, the prenatal exposure of benzine and exposure to paints of the mothers prior to disease onset were risks of high significance. The foregoing results suggest that exposure to occupational and environmental factors of the parents may play an etiologic role in childhood leukemia.
Adolescent↗
Lipoprotein(a) levels in Japanese children with IDDM.
Explore the source record for details and available documents.
Adolescent↗
Relationship between serum levels of methylguanidine and glycemic control in IDDM children.
OBJECTIVE: To examine the serum levels of methylguanidine in IDDM children and compare them with markers for glycemic control. Reports have indicated that active oxygen, which damages various tissues, increases in diabetes mellitus. The increase of active oxygen is one of the risk factors for diabetic complications. The synthesis of methylguanidine, a metabolic product of guanidine, is mainly regulated by active oxygen. RESEARCH DESIGN AND METHODS: Forty-eight children with IDDM (mean age 13.3 yr) and 17 age-matched nondiabetic control subjects were studied. Diabetic children were divided into a well-controlled group (HbA1c < 8%, n = 24) and a poorly controlled group (HbA1c > 8%, n = 24). Serum concentrations of methylguanidine were measured by enzymatic assay. RESULTS: Levels of methylguanidine in the poorly controlled group (1.31 +/- 0.08 microM) were significantly higher than those in both the well-controlled group (0.85 +/- 0.08 microM) and the control group (0.59 +/- 0.11 microM), respectively (P < 0.01). Methylguanidine levels showed a positive correlation with the levels of HbA1c (P < 0.01) or fructosamine (P < 0.01). No significant correlations were noted between methylguanidine levels and age, sex, duration of diabetes, or insulin dose. CONCLUSIONS: Our data indicate that the levels of methylguanidine in IDDM children might be affected by glycemic control and that the determination of serum methylguanidine levels could be a useful test for evaluating the state of diabetic control.
Biomarkers↗