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Biomedical subjects

Y Nagaki

Publications and source records attributed to Y Nagaki.

At least 37 records · Page 2Linked to original sources

Idiopathic sclerosing inflammation of the upper eyelid.

Idiopathic sclerosing inflammation has commonly been found in the diffuse orbital tissues. We report the inflammation of the right upper eyelid in a 65-year-old man. Computed tomography and magnetic resonance imaging showed a diffuse mass localized only in the right upper eyelid. Histologic study of the excised specimen revealed dense collagenous tissue with sparse infiltration of mixed inflammatory cells. Immunohistochemical study showed that the inflammatory cells were largely composed of T cells (UCHL-1), histiocytes (PG-M1) and scattered plasma cells (immunoglobulins). No L26-positive B cells were found. We believe that idiopathic sclerosing inflammation of the upper eyelid, as demonstrated in our patient, may be rare.

Aged↗

Highly selective aldose reductase inhibitors. 3. Structural diversity of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids.

Accumulation of intracellular sorbitol, the reduced product of glucose, catalyzed by aldose reductase (AR) (EC 1.1.1.21), is thought to be the cause of the development of diabetic complications. Our attention is focused on finding compounds which inhibit AR without significantly inhibiting aldehyde reductase (ALR) (EC 1.1.1.2). The uracil or 2,4-dioxoimidazolidine skeleton having the benzothiazolyl or 4-chloro-3-nitrophenyl group as an aryl part indicated not only extremely high AR inhibitory activity but also AR selectivity. The ratio of IC50(ALR)/IC50(AR) of 3-[(5-chlorobenzothiazol-2-yl)methyl]-1,2,3,4-tetrahydro-2,4- dioxopyrimidine-1-acetic acid (47d) was more than 17 500. The uracil skeleton with the benzothiazolyl moiety seemed to be the best combination for selective AR inhibition.

Acetates↗

Central retinal vein occlusion in a woman receiving bromocriptine.

We evaluated a unilateral retinal vascular abnormality in a 34-year-old woman receiving bromocriptine mesylate for the suppression of postpartum lactation. After using bromocriptine, 2.5 mg twice daily for 1 week, the patient complained of metamorphopsia in the left eye. A central retinal vein occlusion was found. We believe that central retinal vein occlusion in patients receiving bromocriptine, as demonstrated in our patient, is rare.

Adult↗

Highly selective aldose reductase inhibitors. II. Optimization of the aryl part of 3-(arylmethyl)-2,4,5-trioxoimidazolidine-1-acetic acids.

Accumulation of intracellular sorbitol, the product of glucose reduction catalyzed by aldose reductase (AR) [EC 1.1.1.21], is thought to be the main culprit in the development of diabetic complications. A series of 3-arylalkyl-2,4,5-trioxoimidazolidine-1-acetic acids was prepared and tested for inhibitory activities towards AR and aldehyde reductase (ALR) [EC 1.1.1.2]. These derivatives showed strong inhibitory activity against AR without markedly inhibiting ALR. In particular, the compounds with 3-nitrophenyl, 4-chloro-3-nitrophenyl, and chloro-substituted benzothiazolyl groups as the aryl part showed powerful AR-inhibitory activity. The chloro-substituted benzothiazolyl compound showed an AR selectivity of more than 5,000 fold.

Aldehyde Reductase↗

Highly selective aldose reductase inhibitors. 1. 3-(Arylalkyl)-2,4,5-trioxoimidazolidine-1-acetic acids.

A series of 3-(arylalkyl)-2,4,5-trioxoimidazolidine-1-acetic acids (1) was prepared and tested for aldose reductase (AR) and aldehyde reductase (ALR) inhibitory activities. These compounds showed strong inhibitory activity against AR without significant inhibitory activity for ALR. The ratio of IC50(ALR)/IC50(AR) was > 1000 in some compounds. On the basis of pharmacological tests such as the recovery of reduced motor nerve conduction velocity and toxicological profile, 3-(3-nitrobenzyl)-2,4,5-trioxoimidazolidine-1-acetic acid (NZ-314) was selected as the candidate for clinical development.

Acetates↗

Primary cornea guttata in Japanese patients with cataract: specular microscopic observations.

To evaluate the prevalence of primary cornea guttata (the first stage of Fuchs' dystrophy) in Japanese patients, we retrospectively examined specular photomicrographs of patients' cataracts. Primary cornea guttata in subjects without corneal inflammation was defined as dark areas, seen on specular microscopy, and irregular refractile dots, observed with slit-lamp microscopy. In 107 patients with cataract (211 eyes), primary cornea guttata was found in 4 women (7 eyes), aged 56 to 76 years. One eye of patient 4, who had a history of angle-closure glaucoma and laser iridotomy, had bullous keratopathy. We also examined 16 relatives (32 eyes) of these 4 affected patients (probands), and found 2 women (4 eyes) with primary cornea guttata. No hereditary influence was identified. We believe that the incidence of primary cornea guttata (Fuchs' dystrophy) in Japan is lower than that in North America.

Adult↗

Cross-species transplantation of photoreceptors with tacrolimus hydrate (FK506) treatment.

Photoreceptors from normal neonatal or transgenic neonatal mice with normally developing retinas were transplanted into the subretinal spaces of normal rats. The animals with transplants received either immunosuppressive treatment with tacrolimus hydrate for the first two weeks after transplantation or no treatment. At 4 weeks after transplantation, graft survival occurred only in rats treated with tacrolimus. In 7 of the 12 treated eyes, photoreceptors survived at least 4 weeks after transplantation. Relatively mature outer segments were found only in 2 eyes in which the retinal grafts formed rosettes.

Animals↗

Effect of Neurotropin on the activation of the plasma kallikrein-kinin system.

Bradykinin (BK), an important mediator of allergic reactions and pain induction, is released by the activation of the plasma kallikrein-kinin (K-K) cascade. Neurotropin is a biological material obtained from inflamed rabbit skin inoculated with vaccinia virus and is widely used clinically in Japan as an effective agent for these disorders. Since its mechanism of action is not clearly known, we have investigated the effects of Neurotropin on the human plasma K-K system. In dextran sulfate-activated plasma, Neurotropin inhibited the formation of BK, the cleavage of high molecular weight kininogen (HK) and the formation of kallikrein-C1 inhibitor and activated coagulation factor XII (FXIIa)-C1 inhibitor complexes. Experiments using purified enzyme of the K-K cascade indicated that Neurotropin inhibited surface-mediated activation of coagulation factor XII (FXII) and the activation of prekallikrein by FXIIa. Neurotropin also inhibited the binding of FXII and HK to the activating surface. These data suggest that the ameliorating effects of Neurotropin in allergic disorders and pain syndromes may be related to this ability to inhibit activation of the K-K cascade and consequently the formation of BK.

Animals↗

Neurotoxin-binding activity in the supernatant fraction of the electric organ from Torpedo californica.

We found neurotoxin-binding activities in the supernatant fraction obtained by ultracentrifugation of a homogenate of the electric organ dissected from the electric ray, Torpedo californica. While about half of the activity was estimated as due to acetylcholine receptors in dispersed microparticles, the remainder was unassigned. A part of the latter, detected with alpha-bungarotoxin, eluted ahead of the alpha-bungarotoxin-acetylcholine receptor complex on a Sepharose CL-6B column in the presence of 1% Triton X-100. Another component eluted after this complex. Although these activities were immunologically related to AChR, they were different from AChR in their size and reactivity with Concanavalin A. We are currently seeking to characterize these toxin-binding components at present. The existence of such activities is interesting since they may possibly function in regulating signal transduction at the neuromuscular junction.

Animals↗

Carbohydrate structures of acetylcholine receptor from Torpedo californica and distribution of oligosaccharides among the subunits.

The structure of carbohydrates in acetylcholine receptor (AChR) from Torpedo californica is reported. Oligosaccharides released quantitatively from the whole molecule by N-oligosaccharide glycopeptidase digestion were fractionated by thin-layer chromatography and further purified by high-performance liquid chromatography. We show that more than 70% of the total oligosaccharide chains in Torpedo AChR are of the high-mannose type with the structures (Man)8(GlcNAc)2 and (Man)9(GlcNAc)2. The structure of these oligosaccharides were determined by proton nuclear magnetic resonance spectroscopy. These two types of oligosaccharides were shown to be distributed different proportions in all subunits of Torpedo AChR. We also show that several kinds of complex-type oligosaccharides comprising the rest of the carbohydrate in the protein exist mainly in the gamma and delta subunits. The structure of the carbohydrate moiety that is distributed on the four subunits of AChR was also examined by susceptibility to endo-beta-N-acetylglucosaminidase and sialidase and by binding affinity to lectins, e.g. concanavalin A, leucoagglutinating phytohemagglutinin, and wheat germ agglutinin.

Animals↗

Branch retinal vein occlusion in the right eye and retinal hemorrhage in the left in a patient with classical Tsutsugamushi disease.

PURPOSE: To report branch retinal vein occlusion and retinal hemorrhages associated with tsutsugamushi disease. METHODS: Case report of a 60-year-old woman who complained of fever, chills, headache, lymphadenopathy, and blurred vision in the right eye following an insect bite to the lower right forehead. RESULTS: Serological findings showed elevated titers for the strains of Rickettsia tsutsugamushi. Ophthalmologic examination disclosed bilateral conjunctival injection, flame-shaped hemorrhage in her right fundus, and scattered hemorrhage in her left fundus. Fluorescein angiography demonstrated dye leakage and dilation of capillaries. CONCLUSIONS: Branch retinal vein occlusion associated with classical tsutsugamushi disease, as demonstrated in our patient, may be rare.

Antibodies, Bacterial↗

Effects of alpha(2)-adrenergic agonists on lipopolysaccharide-induced aqueous flare elevation in pigmented rabbits.

PURPOSE: To evaluate the effects of the alpha(2)-adrenergic agonists (clonidine, apraclonidine, and guanfacine) on lipopolysaccharide (LPS)-induced aqueous flare elevation in pigmented rabbits. METHODS: Anterior uveitis was induced with an intravenous injection of LPS (0.5 microg/kg) in an ear vein. The reproducibility of experimental uveitis induced by LPS (0.5 microg/kg) was also determined. Clonidine (0.01, 0.05, 0.25, or 1%), apraclonidine (1%), or guanfacine (1%) was topically instilled in the right eye 30 and 5 minutes before and 30 minutes after LPS application (N = 6 animals, respectively). Clonidine (0.25%) was topically administered three times at 30-minute intervals from 240 or 120 minutes before, or 120 or 240 minutes after LPS application (N = 6 animals, respectively). Then 1 mg/kg of yohimbine was injected into an ear vein 30 minutes before each topical three-time instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% (N = 6 animals, respectively). Aqueous flare was measured with a laser flare-cell meter. Aqueous flare elevation was expressed as the area under the curve (AUC) in arbitrary units. Rabbits received the first LPS intravenous injection, and the control values of the AUC were obtained. Three months later, the alpha(2)-agonist and the second LPS administration were given to the same animals. RESULTS: The AUCs (5,184 +/- 1,255 units) after the first application of LPS were similar to those (5,033 +/- 1,290) after the second application 3 months after the first administration. Topical instillation of clonidine inhibited LPS-induced aqueous flare elevation in a dose-dependent manner (0.01-0.25%). Topical instillation of clonidine 1%, apraclonidine 1% or guanfacine 1% inhibited LPS-induced aqueous flare elevation by 98 +/- 2.0% (mean +/- SD), 86 +/- 14% and 94 +/- 5.7%, respectively. Pretreatment with intravenous yohimbine prevented the inhibitory effect on flare elevation induced by each agent. CONCLUSION: The present findings suggested that topical instillation of some alpha(2)-agonists may have an inhibitory effect on ocular inflammation, which is mediated in part by alpha(2)-receptors.

Administration, Topical↗

Effects of tetramethylpyrazine on prostaglandin E(2)- and prostaglandin E(2) receptor agonist-induced disruption of blood-aqueous barrier in pigmented rabbits.

PURPOSE: To evaluate the effect of tetramethylpyrazine on the elevation of aqueous flare and intraocular pressure (IOP) induced by prostaglandin (PG) E(2) and PGE(2) receptor (EP) agonists. METHODS: PGE(2) or EP agonists (11-deoxy PGE(1), EP(2) agonist; 17-phenyl trinor PGE(2), EP(1) and EP(3) agonist; or sulprostone, EP(1) and EP(3) agonist), 25 microg/mL, were transcorneally administered to pigmented rabbits. Animals were pretreated with tetramethylpyrazine intravenously (10 or 30 mg/kg) or topically (0.1% solution). Aqueous flare was measured using a laser flare-cell meter, and the intensity was expressed as the area under the curve (AUC). Intraocular pressure was measured using a noncontact tonometer. RESULTS: After administration of PGE(2), aqueous flare and IOP increased and then gradually decreased. The AUC of eyes pretreated with tetramethylpyrazine, 10 or 30 mg/kg, intravenously, or topical 0.1% solution, was significantly smaller than that of the controls. The mean Delta IOP of eyes pretreated with tetramethylpyrazine, 30 mg/kg intravenously, was significantly lower than that of the controls. After administration of 11-deoxy PGE(1), aqueous flare increased and then gradually decreased. 17-phenyl trinor PGE(2) and sulprostone did not disrupt the blood-aqueous barrier. The AUC of eyes pretreated with tetramethylpyrazine, 10 or 30 mg/kg, intravenously, before 11-deoxy PGE(1) application was significantly smaller than that of the controls. CONCLUSION: The results indicated that tetramethylpyrazine inhibited PGE(2)- or 11-deoxy PGE(1)-induced elevation of aqueous flare and IOP.

Alprostadil↗

Effects of scutellariae radix extract and its components (baicalein, baicalin, and wogonin) on the experimental elevation of aqueous flare in pigmented rabbits.

PURPOSE: To evaluate the possible inhibitory effects of hot water extract of Scutellariae radix and its major components (baicalein, baicalin, and wogonin) on experimental elevation of aqueous flare in pigmented rabbits. METHODS: To produce aqueous flare elevation in rabbits, prostaglandin E(2) (PGE(2)), 25 microg/mL, was applied to the cornea with the use of a glass cylinder, or lipopolysaccharides (LPS), 0.5 microg/kg, were injected into an ear vein. Animals were pretreated by the oral administration of 150 g/day of food containing 0.02%, 0.07%, or 0.2% (w/w) extract of Scutellariae radix for 5 days, or by intravenous injection of baicalein, baicalin, or wogonin, 60 microg/kg or 600 microg/kg, 30 minutes before experimental uveitis was induced. Aqueous flare was measured with a laser flare-cell meter. Aqueous flare intensity was expressed as the area under the curve (AUC) in arbitrary units. RESULTS: The AUC of PGE(2)- and LPS-induced aqueous flare elevation was 1,343 and 5,066 arbitrary units, respectively. Pretreatment by oral administration of 0.07% or 0.2% extract of Scutellariae radix did not inhibit PGE(2)-induced aqueous flare elevation (AUC: 1,252 and 1,210, respectively), but it did inhibit LPS-induced aqueous flare elevation (AUC: 2,248 and 1,973, respectively). Pretreatment by intravenous injection of 600 microg/kg of baicalein, baicalin, or wogonin inhibited LPS-induced aqueous flare elevation (AUC: 2,289, 2,163, and 1,509, respectively). Pretreatment with 60 microg/kg of wogonin also inhibited LPS-induced aqueous flare elevation (AUC: 1,980). CONCLUSION: Hot water extract of Scutellariae radix may have an inhibitory effect on experimental anterior uveitis induced by LPS in pigmented rabbits.

Animals↗

Effect of topical betaxolol on acute rise of aqueous flare induced by prostaglandin E(2) in pigmented rabbits.

PURPOSE: To evaluate the effects of topical betaxolol on experimental ocular inflammation. METHODS: Transcorneal diffusion of 25 microg/mL (7.09 x 10(-2) mmol/L) of prostaglandin E(2) (PGE(2)), placed in a glass cylinder, was employed to induce aqueous flare elevation in pigmented rabbits. Betaxolol was administered topically before PGE(2) application. Aqueous flare was measured with a laser flare cell meter. RESULTS: Four-, two-, and one-time topical instillations of betaxolol inhibited the PGE(2)-induced aqueous flare elevation by 44% +/- 8%, 32 +/- 7%, and 8 +/- 6%(mean +/- SD), respectively. The inhibition of flare elevation was dependent on the number of betaxolol instillations. CONCLUSION: Topical betaxolol has an inhibitory effect on PGE(2)-induced aqueous flare elevation in rabbit eyes.

Acute Disease↗

Orbital lymphoma of mucosa-associated lymphoid tissue in a patient with rheumatoid arthritis.

A 75-year-old male with rheumatoid arthritis complained of proptosis of the left eye. On examination, 6-mm left proptosis was seen. A hyperemic and swollen optic disc was visible in the left fundus. Laboratory test results showed positive rheumatoid factor. Computed tomography and magnetic resonance imaging showed a mass lesion in the left orbit. Histopathologic study of the excised specimen revealed centrocyte-like cells and lymphoplasmocytoid cells. Immunohistochemical study showed positive staining of CD 20 (B cells) and lambda light chain (immunoglobulin). The combination of rheumatoid arthritis and lymphoma of mucosa-associated lymphoid tissue in the orbit, as demonstrated in our patient, is rare.

Aged↗

Seasonal allergic conjunctivitis induced by Japanese pear pollen.

PURPOSE: To evaluate the ocular findings in patients with Japanese pear (Pyrus pyrifolia Nakai) pollinosis. METHODS: Twenty-two farmers working on artificial pollination in Japanese pear orchards were examined for ocular itching, conjunctival conditions, presence of eosinophils in the conjunctival specimen, and nasal symptoms. Serum IgE antibody to Japanese pear pollen was determined in 16 farmers. RESULTS: Of the 22 subjects, 3 (Nos. 3, 4, and 13) exhibited ocular itching, conjunctival hyperemia, eosinophils in the conjunctival specimen, and positive serum IgE antibodies to Japanese pear pollen. In these patients, the conjunctivitis disappeared after treatment with topical cromoglycate. CONCLUSION: The present study demonstrated that seasonal allergic conjunctivitis may be induced by Japanese pear pollen (entomophilous flower pollen).

Adult↗

Bilateral angle closure glaucoma and visual loss precipitated by antidepressant and antianxiety agents in a patient with depression.

A 71-year-old woman with depression had been treated with an antidepressant (maprotiline) and antianxiety agents (clotiazepam and alprazolam). She had previously complained of ocular pain and blurred vision. However, thorough ocular examination was not performed at those times. On examination, visual acuity was no light perception OD and hand motion OS. Intraocular pressures were 33 mm Hg OU. Moderately dilated pupils, atrophic irises, shallow anterior chambers and closed angles were seen in both eyes. Despite treatment, her visual acuity decreased to no light perception bilaterally. Psychiatrists and ophthalmologists should be aware that antidepressants and antianxiety agents can precipitate angle closure glaucoma in susceptible eyes.

Adrenergic beta-Antagonists↗