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Y Nagae

Publications and source records attributed to Y Nagae.

33 records · Page 2Linked to original sources

Effect of estrogen on induction of micronuclei by mutagens in male mice.

The effect of estrogen on the induction of micronucleated polychromatic erythrocytes (MPCE) by mutagens was examined in male mice. In the dose-response study, a dose-related inhibition of the mitomycin C (MMC)-induced MPCE frequency by estradiol (E2) treatment was observed. In the time study, inhibitory effects of E2 on MPCE frequency by MMC were observed when MMC was administered at 0 or 1 day after injection of E2. The most effective protocol for inhibition was when E2 and MMC were used on the same day. Of mutagens other than MMC, only vincristine (VCR) showed a significant decrease in MPCE frequency when used together with E2. Benzo[a]pyrene (BaP) and 5-fluorouracil (5-FU) showed no significant decrease in MPCE frequency. The data suggest that the induction of micronuclei by mutagens is inhibited by treatment with estrogen, and this could result in a sex difference in the sensitivity of mice employed in the micronucleus test. Mechanisms of the inhibitory effects of estrogen are discussed; these might include a suppression of erythropoiesis and a possible effect on the cell membrane permeability of erythroblasts.

Animals↗

Effect of estrogen replacement on liver function in ovariectomized rats.

The effect of estrogen (17 beta-estradiol; E2) replacement on the liver function was examined in ovariectomized rats. Ovariectomy decreased serum transaminase activity and physiological dosage levels of E2 replacement returned the activity up to or above non-ovariectomized levels. Under the conditions of this experiment the elevated serum transaminase levels in the E2 replacement were not coincident with histological changes suggestive of liver dysfunction. The elevations of both serum glutamic oxaloacetic transaminase (GOT) and serum mitochondrial GOT were accompanied by increased hepatic tissue activity, suggesting that the elevated serum levels can be attributed to the accelerated synthesis of the enzymes. On the other hand, the elevation of serum glutamic pyruvic transaminase was not accompanied by increased tissue activity in the original organs, namely liver, kidney, heart and skeletal muscle. Ovariectomy decreased serum albumin and inhibited development of rough endoplasmic reticulum in the liver, and E2 replacement returned them up to or above the non-ovariectomized levels.

Alanine Transaminase↗

[The effect of recombinant epidermal growth factor in corneal angiogenesis].

Recent advances in genetic engineering techniques have enabled large-scale manufacture of human epidermal growth factor (hEGF), making possible the clinical use of this particular agent in treating a variety of corneal epithelial disorders. In view of future application to humans, it has to be determined whether hEGF could induce neovascularization in the cornea upon topical instillation, since the angiogenic effect of mouse EGF on the cornea in vivo has been reported. For this, a sheet of slow-release form polymer (EVA) containing hEGF was surgically implanted into the rabbit corneal stroma in search for subsequent corneal neovascularization. EVA sheets contained one of the following agents: (1) 250ng hEGF, (2) 500ng hEGF, (3) 250ng bFGF (positive control), (4) vehicle alone (negative control). On 5 and 14 days after implantation, the corneas were excised, sectioned, and stained with hematoxylin and eosin for histological evaluation. Slit lamp examination revealed that marked neovascularization developed in the corneas when EVA sheets containing bFGF were implanted. A number of polymorphonuclear leukocytes were accumulated around the implants. However, neovascularization did not occur in the corneas when EVA sheets containing either concentrations of hEGF or vehicle alone were implanted. Only a few polymorphonuclear leukocytes infiltrated. This result indicates that as much as 500ng hEGF does not induce corneal neovascularization.

Animals↗

Effect of erythropoietin on the micronucleus test.

The micronucleus test is used widely as an in vivo short-term assay for potential carcinogens. In the present study, results of the micronucleus test were affected by the rate of erythropoiesis in the bone marrow erythropoietin, a growth factor for the erythroblast, which was used to induce erythropoiesis. The highest frequency of micronucleated polychromatic erythrocytes (MPCE) and a dose-response relationship between erythropoietin doses and MPCE frequency were seen 30 hr after injection of 1,1-dimethylhydrazine (DMH) to mice administered 24 hr previously with erythropoietin. The effect of erythropoietin was maximal when erythropoietin was given 24 hr before DMH, indicating that accelerating the multiplication of erythroblasts will increase the frequency of micronuclei induced by mutagens. Induction of MPCE in the bone marrow by four other compounds--benzo(a)pyrene, 2-naphthylamine, mitomycin C, and vincristine--was also increased by pretreatment with erythropoietin.

1,2-Dimethylhydrazine↗

The micronucleus test and erythropoiesis. Effects of erythropoietin and a mutagen on the ratio of polychromatic to normochromatic erythrocytes (P/N ratio).

It is considered that a decrease of the ratio of polychromatic erythrocytes (PCE) to normochromatic erythrocytes (NCE) (P/N) in the micronucleus test is an indicator of bone marrow toxicity induced by mutagens. However, the exact meaning of fluctuation in the P/N ratio is not yet known. We have studied this point by counting the total number of erythrocytes and nucleated cells in the bone marrow following various treatments. The P/N ratio decreased gradually with time after administration of mitomycin C. Our data suggest that the decrease of P/N ratio was attributable to an increase in the numbers of the denominator, i.e. NCE, caused by rapid differentiation and multiplication or denucleation of erythroblasts which remained in the bone marrow instead of entering the peripheral blood stream. A decrease of P/N ratio was also observed in the early phase after administration of erythropoietin, an agent which induces differentiation and multiplication of erythroblasts. This phenomenon might result from an increase of PCE delivery into the blood circulation. However, following the initial decrease, the P/N ratio increased gradually 48 h after administration of erythropoietin. It is supposed that this increase probably resulted from an increase in PCE in the bone marrow due to the direct effects of erythropoietin on erythropoiesis. The drastic change in erythropoiesis in the bone marrow induced by either mutagen or erythropoietin treatment will affect the fluctuations of the P/N ratio or the number of micronucleated erythrocytes per non-micronucleated erythocytes in the micronucleus test. This contrasts with the original explanation for such fluctuations which attributed them to replenishment of the marrow by peripheral blood.

Animals↗

Effect of dietary alpha-linolenate/linoleate balance on mean survival time, incidence of stroke and blood pressure of spontaneously hypertensive rats.

Following the suckling period, stroke-prone spontaneously hypertensive rats (SHR-SP) were fed semi-purified diets supplemented either with safflower seed oil (rich in linoleic acid) or with perilla seed oil (rich in alpha-linolenic acid). The mean survival time of male SHR-SP fed the perilla diet was longer than that fed the safflower diet by 17% (p less than 0.001) while the difference was 15% in female SHR-SP (p less than 0.05). The mean survival times of female SHR-SP were more than 40% longer than those of male SHR-SP in both dietary groups. Post-mortem examinations of brains revealed apoplexy-related symptoms as the major cause of the death in both dietary groups. The systolic blood pressure was lower by ca. 10% (21 mmHg) in the perilla group than in both the safflower group and conventional diet group. The eicosapentaenoate (20:5 n-3)/arachidonate (20:4 n-6) ratio of platelet phospholipids in spontaneously hypertensive rat (SHR), a measure of platelet aggregability, was much higher in the perilla group than in the safflower group. Thus, increasing the dietary alpha-linolenate/linoleate ratio resulted in an increased mean survival time of SHR-SP rats, possibly by lowering blood pressure and platelet aggregability.

Animals↗

Ligneous conjunctivitis: a case report.

BACKGROUND: Ligneous conjunctivitis is a rare condition characterized by chronic, recurrent conjunctivitis associated with pseudomembrane, and it may involve other mucous membranes in the mouth, nasopharynx, trachea, and vagina. We examined and treated a case of presumed ligneous conjunctivitis. CASE: The patient was a 10-year-old boy. His chief complaints were visual impairment, discomfort, and discharge, but no itching in his eyes. His upper eyelids appeared thick without swelling. He had a past history of surgery for lid entropion. His two siblings had similar follicular conjunctivitis. OBSERVATIONS: This case exhibited several characteristics of ligneous conjunctivitis, such as large follicles, recurrent pseudomembrane and normal level IgE in the serum. Indispensable characteristics of vernal keratoconjunctivitis, strong itching, and extensive papillary formation, were not found. In spite of the lack of woody hardness of the conjunctiva, other clinical findings led to the diagnosis of ligneous conjunctivitis. Definite histological diagnosis was not obtained, because of the lack of common histological characteristics among previously reported cases with ligneous conjunctivitis. The boy had developed corticosteroid glaucoma after instillation of dexamethasone 0.1% for 7 months at a previous time. We successfully treated this case with combined instillation of fluorometholon and cyclosporin after trabeculotomy. CONCLUSIONS: Ligneous conjunctivitis must be considered as one type of differential diagnosis of vernal keratoconjunctivitis. Cyclosporin is an effective alternative for the treatment of ligneous conjunctivitis, especially in a case with a possible history of corticosteroid glaucoma.

Child↗