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Biomedical subjects

Y Mimura

Publications and source records attributed to Y Mimura.

At least 55 records · Page 3Linked to original sources

[Endogenous uveitis in disseminated intravascular coagulation induced by endotoxin].

A study was made of endogenous uveitis in experimental disseminated intravascular coagulation (DIC) in rabbits. Endotoxin was injected intravenously twice with a 24-hour interval. The time courses of the following were examined: 1) aqueous flare using a laser flare-cell meter 2) the number of leukocytes in the peripheral blood 3) the tumor necrosis factor (TNF) activity in the serum and 4) histopathological changes in the eye, lung, liver and kidney. Aqueous flare increased at 1 hour and was maximal at 6 hours, accompanied by a rapid increase in TNF activity at 1 hour following the first endotoxin administration. The number of leukocytes decreased to 963 +/- 266 cells/mm3 at 1.5 hours with subsequent leukocytosis within 12 hours. After the second injection of endotoxin, the aqueous flare peaked in 30 minutes and was twice as high as the first peak. Leukocyte number and TNF activity showed the same behavior. However, TNF activity was 20% that of the first peak. Histopathological examination indicated fibrin formation in the small vessels of systemic organs within 3 hours following the second administration of endotoxin. Endotoxin induced uveitis was induced in experimental DIC, and leukocytes and TNF activity may thus perform important roles.

Animals

Effects of oxygen supply on protein metabolism in surgically injured rats. Oxygen as a nutrient.

The effect of various inspired oxygen concentrations on protein metabolism after surgery was investigated in rats. Surgical injury was produced by transecting the stomach. Rats were divided into three groups, i.e., a hyperoxic group, a hypoxic group, and a normoxic control group, which were supplied with 40%, 10%, and 21% oxygen, respectively, for 7 days after operation. All rats were fed intravenously (257 kcal/kg/day, kcal/N: 185.5) and whole-body protein turnover was measured using the constant infusion of 15N glycine technique developed by Picou and Taylor-Roberts. For six days after operation, the cumulative nitrogen balance was negative for the hypoxic rats, while hyperoxic rats showed a positive balance that was significantly higher than in control rats (p less than 0.01). Protein synthesis and breakdown rates increased markedly and the rate of synthesis exceeded that of breakdown in the hyperoxic group, but in the hypoxic group synthesis remained unchanged while breakdown increased moderately. These results indicate that oxygen, as a nutrient, is effective for improving postoperative protein metabolism.

Animals

Effects on herpes simplex virus type 1 of combined use of interferon-beta and anti-herpetic agents in vitro.

It has been shown that the use of interferon (IFN) alone has little or no therapeutic effect in the treatment of herpetic keratitis. However, IFN used in combination with anti-herpetic agents has high therapeutic efficacy. This interaction between IFN and anti-herpetic agents has not been elucidated clearly. In this study, the interaction between human fibroblast interferon (HuIFN-beta) and anti-herpetic agents, 5-iodo-2'-deoxyuridine (IDU), aciclovir (ACV) and 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG), was studied in vitro using VERO cells. After the formation of a monolayer of VERO cells, HuIFN-beta of various concentrations was added to the maintenance medium. After 24 hours incubation, the medium was removed and herpes simplex virus (HSV) type 1 was inoculated on the VERO cells. Then, anti-herpetic agents were added to the medium in various concentrations. After 48 hours incubation, plaques were counted and the reduction rate in numbers of plaque was calculated. It was found that the combination of HuIFN-beta with IDU, ACV or DHPG worked synergistically in the inhibition of HSV replication.

Acyclovir

Synthesis and conformational analysis of Aib-containing peptide modelling for N-glycosylation site in N-glycoprotein.

A tetrapetide containing an Aib residue, Boc-Asn-Aib-Thr-Aib-OMe, was synthesized as a peptide model for the N-glycosylation site in N-glycoproteins. Backbone conformation of the peptide and possible intramolecular interaction between the Asn and Thr side chains were elucidated by means of n.m.r. spectroscopy. Temperature dependence of NH proton chemical shift and NOE experiments showed that Boc-Asn-Aib-Thr-Aib-OMe has a tendency to form a beta-turn structure with a hydrogen bond involving Thr and Aib4 NH groups. Incorporation of Aib residues in the peptide model promotes folding of the peptide backbone. With folded backbone conformation, carboxyamide protons of the Asn residue are not involved in hydrogen bond network, while the OH group of the Thr residue is a candidate for a hydrogen bond in DMSO-d6 solution.

Amino Acid Sequence

N.m.r. study on conformation of Ac-Thr(alpha-GalNAc)-Ala-Ala-OMe as a model for mucin type glycoprotein.

This study report on the results of high resolution 1H n.m.r. investigations on Ac-Thr(alpha-GalNAc)-Ala-Ala-OMe 1 as a mucin type model glycopeptide of antifreeze glycoprotein (AFGP) in both dimethyl sulfoxide (DMSO) and H2O. The temperature dependence of amide proton chemical shifts strongly suggested the presence of the intramolecular hydrogen bond between the amide proton of GalNAc and the carbonyl oxygen of the Thr residues. Due to this bond, the orientation of the sugar residue of 1 appears to be fairly restricted relative to its peptide backbone. Despite the lack of the clear evidence for such intramolecular hydrogen bond in H2O, 1H coupling constant data suggested the structural similarity of 1 in DMSO and H2O, indicating the presence of the intramolecular hydrogen bond even in H2O, which may play an important role in determining the orientation of the sugar moiety with respect to the peptide backbone in glycoprotein.

Amino Acid Sequence

Production of prostaglandin E2 rather than E1 in experimental ocular inflammation of rabbit.

The chopped anterior uvea of rabbit was allowed to react with exogenous [1-14C] arachidonic acid or prostaglandin (PG)H2. Several cyclooxygenase products such as PGD2, PGE2 and PGF2 alpha were produced. In the presence of glutathione PGE2 was a major product. When uveitis was induced by injection of bovine serum albumin into the vitreous body, there was a marked invasion of leukocytes. PGE2 in the aqueous humor increased about 3-fold as determined by radioimmunoassay using anti-PGE2 antibody cross-reacting with PGE1. Extracts from the inflamed aqueous humor and the incubation medium of chopped anterior uvea or peripheral polymorphonuclear leukocytes were analyzed by reverse-phase high-performance liquid chromatography, which allowed separation of PGE2 and PGE1. In all these preparations PGE2 was an almost sole immunoreactive PG, and PGE1 was hardly detectable in sharp contrast to an earlier report (Eakins et al.: Nature 239: 248 (1972].

Animals

[The dynamics of leucocytes and complements in endotoxin induced uveitis].

The dynamics of leukocytes, complement and tumor necrosis factor (TNF) were studied in endotoxin induced uveitis (EIU) in rats. Endotoxin was administered to footpads and the time courses of the following were examined: 1) the number of leukocytes in peripheral blood 2) the number of leukocytes and protein concentration of aqueous humor 3) complement (CH50, C1, C3, C5) in serum and aqueous humor 4) TNF in serum 5) histological changes in the eyes, lungs, liver, and skin. The number of leukocytes in peripheral blood decreased to one third that of controls during three to six hours after endotoxin administration, but increased thereafter along with the number of leukocytes and protein concentration in aqueous humor. More leukocytes were observed than in controls in the small vessels of the iris, lung, liver and skin, some of which attached to the vascular endothelium. Serum C3 increased and serum C5 transiently decreased after endotoxin administration. Serum TNF reached a peak (3500 IU/ml) at 1.5 hours and rapidly decreased subsequently. It is suggested that the adhesion of leukocytes to vascular endothelium and the activation of complement system may play important roles in the development of EIU.

Animals

[Nutritional support in critically ill patients; with special reference to fat emulsion and carnitine].

Energy metabolism of fat emulsion was studied in rats with septic condition. The results indicate that fat emulsion was rapidly eliminated from the blood stream and metabolized readily even in such condition. Based on these findings, we have actively employed fat emulsion clinically as an energy source of septic patients. In septic rats, it was demonstrated that levels of carnitine decreased and that this decrease was based upon a decrease of synthesis. When carnitine was administered together with fat emulsion, the energy metabolism returned to approximately normal level. This reports also describes the absorption and utilization of orally administered fat in septic rats.

Animals

Insulin resistance of adjuvant-induced granuloma pouch formation in genetically diabetic KK-CAy mice.

The characteristics of adjuvant-induced pouch granuloma in genetically diabetic KK-CAy mice with hyperinsulinemia were investigated. Both the dose-response relationship and the time-course experiments showed that the wet weight of pouch granuloma in diabetic KK-CAy mice was lower than in ddY normal mice. Insulin treatment enhanced granuloma formation in KK-CAy mice, and it restored the suppressed DNA content in the granuloma tissue to the level in ddY mice. Although the DNA content was dose-dependently increased by insulin, the ratio of DNA content to granuloma weight was constant. In severely diabetic mice, the granuloma weight was not different from that in normoglycemic mice, despite significantly higher blood insulin levels and greater body weight. Insulin stimulated granuloma formation in severely diabetic KK-CAy mice only when higher doses (1 mg/kg) were given. This evidence suggests that suppression of granuloma formation in diabetic KK-CAy mice is due to insulin resistance and that restoration requires pharmacological doses of insulin.

Animals

Side effects in the treatment of herpetic keratitis.

Various side effects due to antiherpetic drugs observed in the last ten years in our department were studied. A total of 132 patients were treated with 5-iodo-2'-deoxyuridine (IDU), 69 with trifluorothymidine (F3T), 58 with acyclovir (ACV) and 33 with adenine arabinoside (ara-A). Patch tests were routinely done when patients exhibited contact dermatitis. Of the patients treated with IDU, 3 (2.3%) showed contact dermatitis, 2 (1.5%) follicular conjunctivitis and 1 (0.8%) punctate keratopathy. Of the patients treated with F3T, 7 (10.1%) exhibited contact dermatitis and 1 (1.4%) follicular conjunctivitis. In the group treated with ACV, 2 (3.4%) patients showed punctate keratopathy. The patients who received ara-A did not show any side effects. We found that F3T caused contact dermatitis more frequently in Japanese people than Europeans. These side effects were resolved by switching to another anti-herpetic drug without the occurrence of cross-allergy. Therefore, switching to another drug is strongly recommended when patients exhibit side effects in the treatment of herpetic keratitis. Other complications were allergy to atropine and to drug preservative.

Acyclovir

Anti-herpes simplex virus (HSV) effect of 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in rabbit cornea.

The anti-herpes simplex virus (HSV) effect and cytotoxicity of a new nucleoside analogue, 9-(1,3-dihydroxy-2-propoxymethyl)guanine (DHPG) in rabbit cornea were studied. In tests of the anti-HSV effect of DHPG, even 0.03% ointment, given 5 times per day for 2 days, prevented lesion formation. The preventive effect of DHPG was much stronger than that of acyclovir (ACV) or 5-iodo-2'-deoxyuridine (IDU). In tests on the therapeutic effect of DHPG against dendritic ulcers, 0.3% ointment, given 5 times per day for 4 days, had a dramatic therapeutic effect. The effect was stronger than that of 3% ACV or 0.5% IDU ointment. Application of 0.3%, 1% or 3% DHPG ointment to normal rabbit corneas, 5 times per day for 2 weeks resulted in no histopathological abnormalities. The above results show that DHPG is superior to ACV or IDU for treatment of HSV infections.

Acyclovir

Superoxide in ocular inflammation: human and experimental uveitis.

A possible involvement of superoxide in the pathogenesis of uveal inflammation in man and experimental animals was investigated. Superoxide production by the leukocytes of Behcet patients was significantly higher in the attack phase than in the remission phase. Leukocyte superoxide generation was also enhanced in guinea pigs with S-antigen-induced experimental autoimmune uveoretinitis (EAU). If the animals were treated with superoxide dismutase (SOD) at the onset of EAU, aqueous humor cell count was significantly lower than that of control (i.e., without SOD treatment). Infiltration of the inflammatory cells in the anterior retina was markedly reduced in SOD-treated animals. A similar protective effect of SOD against tissue damage was also observed in a bovine serum albumin-induced passive Arthus type uveitis in rabbits. These results suggest that superoxide may play a role in causing tissue damage in animal models of ocular inflammation and possibly in Behcet disease.

Animals

Potentiation by retinoic acid of ornithine decarboxylase induction by phytohemagglutinin or phorbol 12-myristate 13-acetate in guinea pig lymphocytes.

Retinoic acid potentiated the increases in ornithine decarboxylase (L-ornithine carboxy-lyase [EC 4.1.1.17]) activity, [3H]difluoromethylornithine binding to ornithine decarboxylase, intracellular levels of polyamines and DNA synthesis in guinea pig lymphocytes stimulated with phytohemagglutinin. The stimulatory effect on the ornithine decarboxylase induction was dependent on the dose of retinoic acid and on the time of addition of the drug. Retinoic acid has to be added not later than 2 h after phytohemagglutinin to elicit the potentiation. Retinyl acetate also potentiated ornithine decarboxylase induction caused by phytohemagglutinin. Both of these retinoids augmented ornithine decarboxylase induction caused by phorbol 12-myristate 13-acetate. The half-life of ornithine decarboxylase activity estimated after addition of actinomycin D was longer in cells treated with phytohemagglutinin or phorbol 12-myristate 13-acetate together with retinoic acid than in cells treated with the mitogen alone. The half-life after addition of cycloheximide was not affected by retinoic acid. These results suggest that the retinoids are stimulators rather than inhibitors of ornithine decarboxylase induction caused by phytohemagglutinin or phorbol 12-myristate 13-acetate in guinea pig lymphocytes and that retinoic acid potentiates the enzyme activity at the transcriptional or posttranscriptional, but not at the post-translational stage.

Animals