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Biomedical subjects

K Dobashi

Publications and source records attributed to K Dobashi.

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

Tissue differences in antioxidant enzyme gene expression in response to endotoxin.

The effect of endotoxin on antioxidant gene expression and antioxidant enzyme activity in homogenates of the heart, liver, and kidney from Sprague-Dawley rats was compared by quantitation of m-RNA and enzyme activities. Alterations in the message level for Cu-Zn superoxide dismutase (SOD), Mn SOD, and catalase varied with the tissue type, length of exposure to endotoxin, and dose of endotoxin. In general, endotoxin treatment reduced Cu-Zn SOD expression in the heart and liver, but had no noticeable effect in the kidney. Mn SOD message levels were increased in the heart and kidney but decreased in the liver. Catalase expression was reduced in the kidney and increased marginally in the heart and liver. With regard to enzyme activity, endotoxin treatment reduced Cu-Zn SOD activity in the heart, liver, and kidney. Mn SOD activity showed little change in the heart, but increased in the liver and, to a lesser extent, in the kidney. Catalase activity showed little change in the heart and kidney but was decreased at 12 h in the liver. The differing responses of tissues to the oxidant stress of endotoxin exposure should be considered when evaluating the effect of endotoxin on antioxidant enzymes.

Animals↗
PubMed1996

Effect of cetirizine on antigen-induced tracheal contraction of passively sensitized guinea pigs.

BACKGROUND: Cetirizine dihydrochloride (cetirizine), a potent histamine H1-receptor antagonist, has been developed as an anti-allergy drug. OBJECT: The anti-allergic effects and mechanism of cetirizine were studied using in vitro assay systems. METHODS: We investigated the effect of cetirizine on antigen-induced contractions of isolated tracheal strips and on chemical mediator release from antigen-stimulated lung chips taken from passively sensitized guinea pigs. We examined the antigen-induced mobilization of Ca2+ in MC/9 mast cells sensitized with IgE. RESULTS: Cetirizine inhibited the antigen-induced contraction of isolated guinea-pig trachea concentration dependently. Pyrilamine, another histamine H1-receptor antagonist, delayed the response but did not change the maximum amplitude. Cetirizine at the concentration of 3 microM also inhibited the antigen-induced release of histamine, leukotriene D4, and leukotriene E4 from guinea pig lung chips. Furthermore, it inhibited the antigen-induced Ca2+ increase in MC/9 mast cells, whereas pyrilamine did not. CONCLUSION: These findings suggest that one anti-allergic mechanism of cetirizine may inhibit mediator release which is, at least partially, mediated by a decrease in the transient Ca2+ influx in mast cells.

Animals↗
PubMed1996

Allergic responses reduce the relaxant effect of beta-agonists but not potassium channel openers in guinea-pig isolated trachea.

This study was conducted to determine whether the relaxant effect of adenosine triphosphate (ATP)-sensitive potassium channel (KATP) openers on airway smooth muscle are reduced during the hyporesponsiveness of beta-adrenergic receptors. Isometric tension was measured and dose-response curves were constructed for levcromakalim (a KATP opener), Y-26763 (another KATP opener), isoprenaline and theophylline in guinea-pig isolated trachea that was challenged with ovalbumin or pretreated in vitro with either isoprenaline or the KATP openers. Antigen challenge in vitro significantly reduced the potency but not the efficacy of isoprenaline in tracheal strips from actively sensitized guinea-pigs. The concentration of drug that produced a half-maximum inhibition (IC50) was 0.014 +/- 0.004 microM in the challenge group versus 0.006 +/- 0.001 microM in the control group (p < 0.05; n = 9). The IC50 of levcromakalim (1.73 +/- 0.17 microM; n = 6) and of theophylline (110 +/- 3.1 microM; n = 6) were unaffected. Exposure to 4 microM isoprenaline for 30 min evoked beta-adrenergic hyporesponsiveness: the IC50 of isoprenaline rose significantly from 0.010 +/- 0.001 to 0.017 +/- 0.002 microM (p < 0.01; n = 6). No effect was observed on the relaxant actions of levcromakalim and theophylline. In contrast, prior incubation with either levcromakalim or Y-26763 (300 microM for 30 min) significantly reduced the subsequent potency and efficacy of levcromakalim, but did not alter the effects of isoprenaline and theophylline. We conclude that the relaxant effect of the adenosine triphosphate-sensitive potassium channel openers was independent of beta-adrenergic hyporesponsiveness in airway smooth muscle of guinea-pigs.

Adrenergic beta-Agonists↗
PubMed1996

[Rapid progression of adenocarcinoma of the lung in a patient with high levels of granulocyte colony-stimulating factor].

A 51-year-old man was referred and admitted to our hospital for further examination of an abnormal shadow on a chest X-ray film. One month before admission, a chest X-ray film had shown no abnormality. On admission, chest X-ray films and computed tomograms showed a tumor shadow in the right hilum, obstructive pneumonia in the right upper lobe, and a right-sided pleural effusion. Cytological examination of the pleural offusion revealed adenocarcinoma. The patients was given supportive care. The tumor grew rapidly and by the 13th hospital day it occupied whole right upper lobe. The patient died on the 21st day after admission. The white blood cell count had increased to 26540/mm3 as the adenocarcinoma grew. Serum granulocyte colony-stimulating factor (G-CSF), which increases the number of neutrophils in blood in vivo was examined. The serum G-CSF level reached 112 pg/ml. On immunohistochemical examination, the tumor cells stained positively with anti-G-CSF monoclonal antibody. The growth of this tumor was more rapid than expected for adenocarcinoma of the lung. These findings suggest that G-CSF induced growth of the tumor.

Adenocarcinoma↗
PubMed1995

Effects of interferon-gamma on cell differentiation and cytokine production of a human monoblast cell line, U937.

The U937 cell, a human monoblast cell line, has been used as a model to study the function of human monocytes. We investigated the effects of interferon-gamma (IFN-gamma) on superoxide anion (O2-) production, cell surface antigens, and cytokine production of U937 cells. IFN-gamma treatment enhanced O2- production of fMLP or PMA-stimulated U937 cells. IFN-gamma increased the ratio of CD23 and CD11b positive cells. The fluorescence intensity of CD14 and CD25 was enhanced by IFN-gamma treatment. U937 cells produced IL-1 alpha, IL-1 beta, IL-6, and TNF-alpha by lipopolysaccharide (LPS) stimulation. IFN-gamma treatment enhanced TNF-alpha production, but decreased IL-6 production. These results suggest that IFN-gamma differentiates U937 cells to monocyte-like cells and it regulates the production systems of IL-6 and TNF-alpha separately in U937 cells.

Antigens↗
PubMed1995

Suppression of anti-Candida activity of murine neutrophils by progesterone in vitro: a possible mechanism in pregnant women's vulnerability to vaginal candidiasis.

Sex steroid hormones were examined for their effect on mycelial growth of Candida albicans, and the inhibitory activity of casein-induced murine peritoneal neutrophils against mycelial growth of C. albicans was examined in vitro using a crystal violet staining method or a [3H]glucose incorporation method. Four steroid hormones, danazol, estradiol, estriol and testosterone had no effect on mycelial growth of C. albicans, but progesterone appeared to convert the growth form of C. albicans from hyphal to yeast. Danazol (10(-6) M) and progesterone (10(-5) M) suppressed anti-Candida activity of neutrophils of non-treated mice, while testosterone, estradiol, and estriol did not. The anti-Candida activity of neutrophils of estradiol-pretreated mice was clearly suppressed by progesterone even at 10(-6) M which corresponded to its plasma concentration in pregnant women in the third trimester. The physiological significance of this suppressive effect of progesterone was discussed in relation to the vulnerability of pregnant women to vaginal candidiasis.

Animals↗
PubMed1995

Effect of an alpha 2-adrenoceptor antagonist, midaglizole, on bronchial responsiveness to histamine in patients with mild asthma.

The purpose of this study was to investigate the effects of midaglizole (MID) and interactions of MID with beta 2-agonists on bronchial hyperresponsiveness (BHR). Thirteen patients with mild asthma were randomized with respect to whether they were taking oral beta 2-agonists, and the investigators were blinded to patients' regular drug regimens. Histamine challenge test was performed before and after oral administration of MID for 1 week (300 mg/day). There was a significant increase in PC20 values in asthmatic subjects on regular therapy with beta 2-agonists (p < 0.05), whereas asthmatics not taking beta 2-agonists showed no significant change in PC20. These results suggest that MID may participate in improved BHR in the presence of beta 2-agonists and play some role in enhancing the effects of beta 2-agonists.

Administration, Oral↗
PubMed1995

Protective effect of an alpha 2-adrenoceptor antagonist, midaglizole, against allergen-provoked late asthmatic responses.

We investigated the effects of midaglizole (MID) on the allergen-provoked early and late asthmatic response (EAR, LAR) in a randomized, single-blind protocol. Four subjects with allergic asthma inhaled the following combinations: (1) allergen alone (control phase); (2) (a) pre- and posttreatment with MID (oral administration of 200 mg), (b) pretreatment with MID (200 mg), or (c) posttreatment with MID (200 mg). MID significantly inhibited the LAR in the three treatment phases (p < 0.05). However, the EAR was not inhibited significantly. These results suggest that MID may participate in the inhibition of the allergen-provoked LAR and may play an important clinical role as an anti-LAR agent.

Adrenergic alpha-Antagonists↗
PubMed1995

Relationships between biochemical abnormalities and anthropometric indices of overweight, adiposity and body fat distribution in Japanese elementary school children.

OBJECTIVE: To determine the anthropometric indices linked to the biochemical risk factors for atherosclerosis in Japanese obese elementary school children, ages ranging from 6 to 12 years. DESIGN: Cross-sectional study of obese children based on fasting blood samples. SETTING: Outpatient clinic of University Hospital. SUBJECTS: 65 consecutive patients with simple obesity (38 boys and 27 girls), and age-matched controls, 184 boys and 205 girls. MAIN OUTCOME MEASURES: Percent obesity and body mass index as indices of being overweight; percent body fat and the sum of four skinfold thicknesses as indices of adiposity; waist-to-hip circumference ratio and waist-to-thigh circumference ratio as indices of body fat distribution. The anthropometric indices were standardized by calculating standard deviation scores based on data from control children. RESULTS: In the obese boys, all six anthropometric indices studied correlated closely with serum biochemical indices, and strong correlations were observed among the indices of overweight, adiposity and body fat distribution. In contrast, only the indices of body fat distribution, not those of overweight or of adiposity, were correlated with serum biochemical indices in the obese girls. No relationship was found between the indices of body fat distribution and the other anthropometric indices in the obese girls. Thus, the profile of the obese girls differed from that of their male counterparts. CONCLUSION: The results suggest that body fat distribution is related to certain biochemical complications of childhood obesity, and that androgyny in fat patterns induces metabolic derangements in children.

Adipose Tissue↗
PubMed1994

Purification and immunoelectron microscopic localization of cellular glutathione peroxidase in rat hepatocytes: quantitative analysis by postembedding method.

To measure quantitatively the intracellular distribution of cellular glutathione peroxidase (GPX) in rat hepatocytes, ultrathin sections were stained by a postembedding immunogold technique. GPX had a specific activity of 1670 Units/mg protein, and was purified 2050-fold from rat liver by means of heat denaturation, ammonium sulfate fractionation, and a series of chromatographic procedures including thiol-Sepharose 4B. The purified GPX was shown to be electrophoretically pure, and was a homotetramer of 22 kDa subunits. Monospecific polyclonal antibodies were raised in rabbits by immunization. By immunoblot analysis, both the light mitochondrial the and cytosolic fractions of rat liver homogenate gave a single band with an identical mobility to that of the purified enzyme. Under the light microscope, hepatocytes showed nuclear staining and granular cytoplasmic staining, corresponding to certain intracellular structures. The labeling density (number of gold particles/microns 2) for GPX obtained by immunoelectron microscopy was 11.9 in the nuclei, 19.6 in mitochondria, 3.32 in peroxisomes, 1.95 in lysosomes, and 9.81 in the cytoplasmic matrix. These results suggest that cellular GPX is present in various compartments of rat hepatocytes, and that the GPX occurs in relatively higher amounts in mitochondria.

Animals↗
PubMed1994

Serum antioxidant status in streptozotocin-induced diabetic rat.

To determine whether decrease in serum antioxidants contributes to the increased oxidative stress, we measured the antioxidant activity (AOA), total peroxyl radical-trapping antioxidant parameter (TRAP), and their component individual antioxidants in the serum of diabetic rats. AOA was assayed as the ability of serum to inhibit lipid autoxidation in brain homogenates. TRAP was assayed as the ability to delay lipid peroxidation induced by an azo initiator. Antioxidants measured were ceruloplasmin, unsaturated iron binding capacity (UIBC) and albumin as components of AOA; and uric acid, protein sulfhydryl and alpha-tocopherol as components of TRAP. AOA was decreased markedly in the diabetics due to the decrease in ceruloplasmin, UIBC and albumin. On the other hand, the directly measured TRAP in the diabetics was unaltered. Uric acid and alpha-tocopherol were increased in the diabetics. However, decrease in unidentified scavengers offset the increase brought about by those antioxidants These results suggest that the decreased metal binding capacity contributes to the increased oxidative stress in the diabetic rats.

Animals↗
PubMed1994

Influence of aging and sex on specific IgE antibody production.

The influence of aging and sex on specific IgE production was evaluated in a non-allergic population aged from 18 to 99 years. Specific IgE against mite antigen and Japanese cedar pollen (JCP) were measured by fluorescence enzyme immunoassay. The incidence and titer of positive anti-mite and anti-JCP IgE antibodies decreased with age, particularly in the aged group. There were slight sex-related changes in IgE production. No significant correlation was noted between anti-mite and anti-JCP IgE antibody levels in the same individual subjects. These findings suggest that the production of specific IgE, as an immunoglobulin class, declines with aging.

Adolescent↗
PubMed1994

[Clinical analysis of benign tumors of the lung].

Benign tumors of the lung occur in low frequency, but its differential diagnosis from malignant tumors such as lung cancer is important. This paper presents as analysis of clinical features of 26 cases operated on for benign tumor of the lung. Histologically there were 15 hamartomas, 8 sclerosing hemangiomas, 2 inflammatory pseudotumors and one clear cell tumor. The roentgenographic appearances were well defined circumscribed solitary nodules in 17 cases (65%), and lobulation and spiculation in 9. Histological diagnosis of benign tumors was not obtained in all cases preoperatively. Minimal resection procedures were performed in 22 cases (85%). No postoperative complications developed.

Adolescent↗
PubMed1993

Immunohistochemical study of copper-zinc and manganese superoxide dismutases in the lungs of human fetuses and newborn infants: developmental profile and alterations in hyaline membrane disease and bronchopulmonary dysplasia.

To determine the late gestational development of copper-zinc (CnZn) and manganese (Mn) superoxide dismutases (SOD) in human lung, immunohistochemical localization was performed for each SOD. The lung samples were taken from five aborted fetuses, four fetuses in which intrauterine death occurred, one full-term neonate, two premature infants with hyaline membrane disease and one premature infant with bronchopulmonary dysplasia (BPD). Morphometry was performed, and the percent area of positive staining was computed. The bronchial epithelium was intensely stained from the early stages of gestation (i.e. 17 weeks), while the staining intensity for both CuZnSOD and MnSOD in the peripheral airways increased gradually during lung development. The mean percent area of the staining for CuZn-SOD and MnSOD from 16 to 38 weeks was increased 30-fold and 8-fold, respectively, and further increases were observed postnatally. CuZnSOD staining was markedly decreased in lungs with respiratory disorders. However, proliferating type II pneumocytes were intensely stained for MnSOD in the BPD lungs, making the staining area 3-fold larger than that in the control lungs. These results clearly depict age-related increases in staining for both CuZnSOD and MnSOD and an alteration in SOD distribution associated with neonatal respiratory disorders.

Bronchopulmonary Dysplasia↗