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Biomedical subjects

N Miyata

Publications and source records attributed to N Miyata.

At least 19 recordsLinked to original sources

Uveitis associated with human T-cell lymphotropic virus type I.

Seroepidemiologic, clinical, and virologic studies were performed to determine whether human T-cell lymphotropic virus type I was closely associated with uveitis in two hospitals. One hospital was in an endemic area of the virus (Miyakonojo, Miyazaki) and the other hospital was in a less endemic area (Kurume). In the endemic area, the seroprevalence of the virus in patients with uveitis without defined causes (35.4%, 62 of 175 patients) was significantly higher than that in patients with nonuveitic ocular diseases (16.1%, 42 of 261 patients), or in patients with uveitis with defined causes (10.3%, eight of 78 patients). The seroprevalence in younger patients (20 to 49 years of age) with uveitis without defined causes in the area was 44.8% (30 of 67 patients), whereas it was only 9.3% (ten of 107 patients) in the other two groups. A similar observation was recorded even in the less endemic area (Kurume). Because the seroprevalence of the virus in the general population is known to be low in younger patients and to increase with age, these findings were interpreted to indicate that the association of human T-cell lymphotropic virus type I with uveitis was significant. Most patients, particularly those aged 20 through 49 years, had an intermediate uveitis characterized by a moderate inflammation in the vitreous body accompanied by an iritis and retinal vasculitis. The ocular symptoms in the patients differed from those of other types of uveitis common in Japan (Behçet's disease, Vogt-Koyanagi-Harada's disease, and toxoplasmosis, for example).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Induction of colon adenocarcinomas in CD rats and lung adenomas in ICR mice by 6-nitrochrysene: comparison of carcinogenicity and aryl hydrocarbon hydroxylase induction in the target organs of each species.

Species and organ specificity of 6-nitrochrysene (6-NC)-induced carcinogenicity and the potential correlation with aryl hydrocarbon hydroxylase (AHH) induction in the target organs were investigated in both sexes of ICR mice and CD rats. Animals received total 6-NC doses of 1.4 mumol/mouse and 14.8 mumol/rat. The first i.p. injection was performed within 24 h of birth, then the animals were subjected to 3 and 5 weekly injections in the mouse and rat cases, and the survivors were sacrificed at weeks 24 and 32, respectively. Adenocarcinomas and dysplasias and/or adenomas of the colon in rats and lung adenomas in mice were observed in animals treated with 6-NC. However, no such lesions were observed in animals treated with the vehicle dimethyl sulfoxide alone. AHH activities in the lung, colon, and liver of each animal after treatment with 6-NC or dimethyl sulfoxide were also investigated. Six-week-old animals received a single 6-NC injection i.p. at the dose of 0.8 mumol/mouse or 8.0 mumol/rat. Animals were sacrificed on day 1 or 7 following injections, when AHH levels were measured. The results indicated enzyme levels in all these organs to be elevated by 6-NC treatment, the induction rate in the mouse lung being the highest. These results showed that 6-NC is carcinogenic for the colon of rats, as well as the lung of mice, and that it also induces AHH activity in both target and nontarget organs.

Adenocarcinoma

Reduction properties of nitrated naphthalenes: relationship between electrochemical reduction potential and the enzymatic reduction by microsomes or cytosol from rat liver.

The nitroreductase activities of rat liver microsomes and cytosol towards various nitrated naphthalenes (1-, 2-mononitro-, 1,3-, 1,5-, 1,7-, 1,8-dinitro-1,3,5- and 1,3,8-trinitronaphthalenes) were characterized as follows. (1) The rates of reduction of nitrated naphthalenes in either microsomal or cytosolic incubation were found to increase in the order of trinitro- > dinitro- > mono-nitronaphthalene, although, in the case of microsomal nitroreduction, trinitronaphthalenes were reduced more rapidly than in cytosol. (2) The effective cofactors, electron donors, in the nitroreduction of nitrated naphthalenes in cytosol were NADH and hypoxanthine, but not NADPH. (3) The nitrated naphthalenes with a nitro group at a beta-position appear to be more easily reduced among the various isomers. The cytosolic nitroreductase activities towards the nitrated naphthalenes were closely related to the single-electron reduction potentials measured by cyclic voltammetry and hence, there was a good relationship between the logarithm of nitroreductase activities and the electrochemical reduction potentials. In microsomes, nitroreductase activities were rather less well related to electrochemical reduction potentials.

Animals

Functional changes in vascular smooth muscle and endothelium of arteries during diabetes mellitus.

To investigate the influence of diabetes mellitus on the responsiveness of the vascular smooth muscle, the effects of various vasoactive agents on the reactivity of the vascular smooth muscle from diabetic animals have been undertaken, focusing on the functional changes in the endothelium, alpha-adrenoceptors, beta-adrenoceptors, voltage-dependent Ca(2+)-channels, receptor-operated Ca(2+)-channels, phosphatidylinositol turnover and potassium channels. Among the functional changes, it is a common phenomenon that decreases in acetylcholine-induced production of cyclic GMP are due to the attenuation of release of endothelium-derived relaxing factor through an impairment of endothelium; this observation was found in both rats and rabbits with diabetes mellitus. These functional changes in diabetes may be responsible for the vascular complications such as coronary heart disease, cerebrovascular disease, and an acceleration in atherosclerosis.

Animals

Changes in responsiveness of the aorta to vasorelaxant agents in genetically diabetic rats: a study in WBN/Kob rats.

The effects of various vasorelaxant agents on aortas from control and genetically diabetic rats were examined. The concentration-response curves for the isoproterenol (ISO)-induced relaxation of both aortic strips with and without endothelium are shifted to the right in diabetic rats. The relaxation responses of diabetic aorta to forskolin and vasoactive intestinal peptide did not differ from those of controls. The relaxation responses of diabetic aorta to cromakalim and nicorandil did not differ from those of controls. These results indirectly indicate that ISO-induced relaxation responses of the aortic strips from genetically diabetic rats decreased, and that this decreased relaxation response of the strips to ISO may be due to decreased density or affinity of beta adrenoceptors on the endothelium and vascular smooth muscle.

Animals

Mutagenicity of nitro-azabenzo[a]pyrene and its related compounds.

The mutagenicity of nitrated benzo[a]pyrene (BP) and the related compounds, 1- and 3-nitrobenzo[a]pyrene (NBP), 1- and 3-nitro-6-cyanobenzo[a]pyrene (N-6-CBP), 1- and 3-nitro-6-azabenzo[a]-pyrene (N-6-ABP), 1- and 3-nitro-6-azabenzo[a]-pyrene-N-oxide (N-6-ABPO) and 1,6- and 3,6-dinitrobenzo[a]-pyrene (DNBP), was investigated. The mutagenic activities of 3-N-6-CBP and 3-N-6-ABP were 117 and 76 times, respectively, that of 3-NBP. In addition, 3,6-DNBP was more mutagenic than 1,6-DNBP. It is suggested that the mutagenic activation differs with the position of NO2 substitution in the chemical structure. A nitro derivative with NO2 substitution at the 3 position of the aromatic ring of BP was more mutagenic than that with the substitution at the 1 or 6 position. The reducibility of DNBPs was then determined by detecting 1- or 3-amino-6-nitrobenzo[a]pyrene (A-6-NBP), a metabolite of DNBP; 3,6- and 1,6-DNBP were reduced to 3- and 1-A-6-NBP at frequencies of 958 +/- 26 and 79 +/- 8, respectively, pmole per mg of protein, when the compound was incubated anaerobically with rat liver S9 mix at 37 degrees C for 15 min. NO2 substituted at the 3 position of the aromatic ring of BP was readily reduced by a microsome enzyme to form an amino derivative. The result suggests that these compounds have a structure-activity relationship between mutagenicity and NO2 substitution of BP.

Animals

Postsurgical inflammation after phacoemulsification and extracapsular extraction with soft or conventional intraocular lens implantation.

A one-year prospective study was conducted in 120 patients to assess the time course of changes in intraocular inflammation after three cataract surgery procedures: planned extracapsular extraction with poly(methyl methacrylate) (PMMA) intraocular lens (IOL) implantation (11 mm incision group), phacoemulsification with PMMA IOL implantation (7 mm incision group), and phacoemulsification with foldable silicone single-piece IOL implantation (4 mm incision group). Each group was carefully matched for patients' ophthalmologic and systemic backgrounds. Patients with hard nuclei were excluded. The degree of inflammation was evaluated by quantitating aqueous flare intensity and cell count with the laser flare-cell meter. In the early postoperative period, both aqueous flare intensity and cell count were highest in the 11 mm incision group followed, in decreasing order, by the 7 mm and 4 mm incision groups. Significant between-group differences were observed at one, two, and seven postoperative days for flare and one day through one week for cells. Both parameters in each group decreased to a similar level one month after surgery, but flare intensity in all groups remained significantly higher than that of age-matched normal controls up to six months postoperatively.

Aged

HTLV-I uveitis: a distinct clinical entity caused by HTLV-I.

Seroepidemiological, clinical and virological studies were carried out in an HTLV-I endemic area to find out if HTLV-I caused an intraocular inflammatory disorder, uveitis. The seroprevalence in patients with uveitis without defined etiologies (62/175, 35.4%) was significantly higher than that in patients with non-uveitic ocular diseases (42/261, 16.1%) or in patients with uveitis with defined etiologies (8/78, 10.3%). Moreover, the seroprevalence in young adults (20-49 years) with uveitis without defined etiologies was 30/67 (44.8%), whereas it was only 10/107 (9.3%) in the other two groups. The uveitis in HTLV-I carriers was characterized clinically by a moderate inflammation of the vitreous body accompanied by a mild iritis and retinal vasculitis. The proviral DNA of HTLV-I was detected by polymerase chain reaction from the inflammatory cells in the anterior chamber in 9 out of 9 seropositive patients with the uveitis, but not in any of the tested patients with other types of uveitis. These data, thus, indicate that HTLV-I causes a specific type of intraocular inflammation, uveitis.

Adult

NAD(P)H-dependent chromium (VI) reductase of Pseudomonas ambigua G-1: a Cr(V) intermediate is formed during the reduction of Cr(VI) to Cr(III).

An NAD(P)H-dependent Cr(VI) reductase (molecular weight = 65,000) was purified from a Cr(VI)-resistant bacterium, Pseudomonas ambigua G-1. Stoichiometric analysis of the enzymatic reaction showed that the enzyme catalyzed the reduction of 1 mol of Cr(VI) to Cr(III) while consuming 3 mol of NADH as an electron donor. Chromium(VI) was reduced to Cr(V) by one equivalent NADH molecule in the absence of the enzyme. Electron spin resonance analysis showed that Cr(V) species (g = 1.979) was formed during the enzymatic reduction. The amount of Cr(V) species formed was about 10 times larger than that of the nonezymatic reduction. These findings show that the Cr(VI) reductase reduced Cr(VI) to Cr(III) with at least two reaction steps via Cr(V) as an intermediate.

Chromatography, Liquid

Age-related changes in endothelium-dependent relaxation in aorta from genetically diabetic WBN/Kob rats.

Experiments were designed to investigate the effects of aging and hyperglycemia on relaxation of the aorta for both endothelium-dependent and -independent agents in Wistar (control) and WBN/Kob (genetically diabetic) rats. The concentration of glucose in serum was elevated significantly in aged (90-92 wk) but not young (13-15 wk) WBN/Kob rats. Endothelium-dependent relaxations of both control and WBN/Kob rats to acetylcholine were reduced by aging. The relaxations induced by acetylcholine in aortic strips were significantly attenuated in both young (nondiabetic) and aged (diabetic) WBN/Kob rats, compared with those from age-matched control vessels, respectively. The concentration-response curves for sodium nitroprusside in aortic strips from both aged control and aged WBN/Kob rats were shifted to the left when compared with those from young rats, respectively. However, the maximal relaxation responses to sodium nitroprusside showed no difference among all vessels studied. The relaxations induced by sodium nitroprusside in aortic strips from both young and aged WBN/Kob rats were similar to those from age-matched control rats, respectively. The relaxations induced by atrial natriuretic peptide showed no difference among all vessels studied. In genetically diabetic rats, functional changes in endothelium occurred before elevation of the levels of glucose in the serum. Thus impaired endothelium-dependent relaxation may play an important role in the high incidence of vascular complications in diabetes mellitus.

Acetylcholine

Effects of CD-349 and 8-BrcGMP on isoproterenol-induced relaxation in rabbit aorta precontracted with endothelin-1.

We investigated the effects of CD-349, a dihydropyridine derivative, on isoproterenol (Iso)-induced relaxation in rabbit aorta precontracted with endothelin-1 (ET-1). The Iso (10(-8)-10(-5) M)-induced relaxation responses in rabbit aorta precontracted with 1-2 x 10(-7) M ET-1 were augmented by pretreatment with CD-349 (10(-9)-10(-5) M) in a concentration-dependent manner. The effects of CD-349 on Iso-induced relaxation of the aortic strips precontracted with ET-1 were inhibited by treatment with methylene blue (10(-5) M) and oxyhemoglobin (10(-5) M), whereas they were augmented by treatment with N omega-nitro-L-arginine (10(-4) M). The Iso-induced relaxation responses were also augmented by pretreatment with 8-Br-guanosine 3',5'-cyclic monophosphate (cGMP) (3 x 10(-6)-3 x 10(-4) M) in a concentration-dependent manner. However, nifedipine (10(-5) M) and nicardipine (10(-5) M) had no effect on Iso-induced relaxation responses of the aortic strips precontracted with 10(-7) M ET-1. CD-349 also augmented forskolin (10(-8)-10(-5) M)-induced relaxation responses of rabbit aorta in a concentration-dependent manner. CD-349 (10(-7)-10(-5) M) increased the levels of cGMP but not of adenosine 3',5'-cyclic monophosphate (cAMP) in a concentration-dependent manner in rabbit aorta without endothelium. Both CD-349 (10(-5) M) and 8-BrcGMP (3 x 10(-5) M) augmented the Iso-induced elevations of cAMP in rabbit aorta without endothelium. These results indicate that CD-349 and 8-BrcGMP can augment Iso-induced relaxation responses by enhancing the accumulation of cAMP.

Animals

Electrical stimulation-evoked release of endogenous taurine from slices of the hippocampus, cerebral cortex and cerebellum of the rat.

Release of endogenous taurine by electrical stimulation of slices of the hippocampus, cerebral cortex, cerebellum and medulla oblongata of the rat was studied and compared with that of alanine and/or gamma-aminobutyric acid (GABA). Electrical stimulation caused a calcium-dependent release of taurine from slices of the hippocampus, cerebral cortex and cerebellum but not from slices of the medulla oblongata. The stimulus-evoked release of taurine in the hippocampus was rapid in onset and declined to baseline fast, which was essentially similar to the time course pattern of the stimulus-evoked release of GABA. In addition, there were distinct regional differences in the relative amounts of taurine released. Electrical stimulation did not release alanine from any regions examined. These results support the hypothesis that taurine plays a neurotransmitter role in the hippocampus, cerebral cortex and cerebellum of the rat.

Alanine

The metabolism of 1,6-dinitropyrene in rat hepatocytes.

This paper reports investigations using hepatocytes to study the metabolism and DNA binding of the environmental contaminant, 1,6-dinitropyrene. Since 1,6-dinitropyrene is not believed to be mutagenic per se, metabolites were synthesized and the metabolism of 1,6-dinitropyrene was subsequently studied in rat hepatocytes. The mode of activation of dinitropyrenes is reduction of one of the nitro groups. Nitroreduction has been shown previously to be oxygen sensitive and therefore the effect of oxygen on the metabolic pattern and DNA binding was investigated by comparing results from aerobic and anaerobic conditions. The binding of [14C]1,6-dinitropyrene equivalents to rat hepatocyte DNA was increased by 15% in the presence of oxygen. Although there was little difference in the rate of 1,6-dinitropyrene metabolism, with or without O2, there was a difference in the metabolic pattern. Under anaerobic conditions there was an increase in the level of the terminal reduction product 1-amino-6-nitropyrene.

Animals

Enhanced contractile effect of phorbol dibutyrate in portal veins from hypertensive rats.

The effects of phorbol 12,13-dibutyrate (PDBu) on portal veins from hypertensive (SHRSP0 and normotensive (WKY) rats were examined. PDBu contracted the strips from SHRSP and WKY in a concentration-dependent manner. However, both twitch contraction and tonic contraction of strips in response to PDBu were enhanced in SHRSP. Treatment with staurosporine reduced contractile response to PDBu in strips from SHRSP. It appears that the activity of protein kinase C in vascular smooth muscle is increased in SHRSP.

Alkaloids

Changes in responsiveness of the canine basilar artery to endothelin-1 after subarachnoid hemorrhage.

The effect of endothelin-1 (ET-1) on the basilar arteries from control and subarachnoid hemorrhage (SAH) dogs were examined. The maximal contraction of the basilar artery in response to ET-1 was markedly decreased in the SAH group. Treatment with 10(-8)M phorbol 12-myristate 13-acetate (PMA) reduced the contractile responses to ET-1 in the basilar arteries from control dogs. ET-1-induced contractions of the basilar arteries from control dogs were similar to those in strips from SAH dogs by the treatment with 10(-8) M PMA. Ca(2+)-induced contraction of the basilar arteries which were depolarized with isotonic K+ (64 mM) were significantly attenuated in SAH dogs. Treatment with PMA also reduced the contractile responses to Ca2+ in the basilar arteries from control dogs. These results indicate that decreased contractile responses of the basilar arteries to ET-1 and Ca2+ in the SAH group may be related to changes in the activity of the protein kinase C in vascular smooth muscle.

Animals

Clastogenicity of 1-nitropyrene, dinitropyrenes, fluorene and mononitrofluorenes in cultured Chinese hamster cells.

The chromosomal aberration test using a Chinese hamster lung cell line (CHL) was carried out on 1-nitropyrene (NP), 3 dinitropyrenes (DNPs), fluorene and 4 mononitrofluorenes with and without metabolic activation (rat S9 mix). The 3 DNPs (1,3-, 1,6- and 1,8-DNP) induced chromosomal aberrations in the absence of S9 mix. The frequencies of cells with aberrations after treatment for 48 h were 43% at 2 micrograms/ml of 1,3-DNP, 55% at 0.1 microgram/ml of 1,6-DNP and 45% at 0.025 microgram/ml of 1,8-DNP, indicating the order of clastogenic potency as 1,8- greater than 1,6- greater than 1,3-DNP. On the other hand, 1-NP, which is known to be a direct-acting mutagen in bacteria, was negative in the chromosomal aberration test without S9 mix, but clearly positive with S9 mix. This effect was dependent on the concentration of the S9 fraction in the reaction mixture. High-pressure liquid chromatography analysis showed that 1-NP was converted by S9 mix to several metabolites, including 1-aminopyrene (AP). The clastogenic activity of 1-AP, however, was equivocal without S9 mix, suggesting that active clastogens other than 1-AP exist. Fluorene induced chromosomal aberrations only in the presence of S9 mix (61.8% at 25 micrograms/ml). 1-, 2-, 3- and 4-nitrofluorene (NF) were more clastogenic in the presence of S9 mix than in the absence of S9 mix, suggesting that NFs were converted to more active clastogens by S9 mix.

Animals