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Biomedical subjects

Y Honda

Publications and source records attributed to Y Honda.

At least 109 records · Page 6Linked to original sources
PubMed2000

Prostaglandin D2 as a mediator of allergic asthma.

Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.

Allergens↗
PubMed2000

Synthesis of viral DNA and late capsid protein L1 in parabasal spinous cell layers of naturally occurring benign warts infected with human papillomavirus type 1.

We investigated human papillomavirus type 1 (HPV1)-specific transcription, viral DNA replication, and viral protein expression in naturally occurring benign tumors by in situ hybridization, 5-bromodeoxyuridine (BrdU) incorporation, and immunohistochemistry and obtained results different from other HPV-infected benign tumors characterized so far. Moderate amounts of transcripts with a putative coding potential for E6/E7, E1, and E2 were demonstrated from the first subrabasal cell layer throughout the stratum spinosum and granulosum. In addition very large amounts of E4 and L1 transcripts were present in the same epithelial layers. This finding was substantiated by the demonstration of L1 and E4 protein already in the bottom-most spinous cell layer. Furthermore massive amplification of the viral DNA as measured by BrdU incorporation and different methods of in situ hybridization took place in the lowest 5 to 10 suprabasal cell layers. These findings are in contrast to the assumption that late gene expression and viral DNA synthesis are restricted to the more differentiated cell layers of the epithelium and point to differences in the regulation of the vegetative life cycle between different papillomavirus types.

Adolescent↗
PubMed2000

Lomerizine, a Ca2+ channel blocker, reduces glutamate-induced neurotoxicity and ischemia/reperfusion damage in rat retina.

We examined the effects of a new Ca2+ channel blocker, lomerizine, on the intraocular hypertension-induced ischemia/reperfusion injury in rat retina and on the glutamate-induced neurotoxicity in rat cultured retinal neurons, and compared its effects with those of a Ca2+ channel blocker (flunarizine) and an N-methyl-D-aspartate receptor antagonist (MK-801). Morphometric evaluation at 7 days after ischemia/reperfusion showed that treatment with lomerizine (0.1 and 1 mg kg(-1), i.v.) prior to ischemia and again immediately after reperfusion dose-dependently reduced the retinal damage. Treatment with MK-801 (1 mg kg(-1), i.v.) before ischemia significantly reduced the resulting retinal damage. Flunarizine (0.1 and 1 mg kg(-1), i.v.) tended to reduce the retinal damage, but its effect did not reach statistical significance. In an in vitro study, pretreatment with lomerizine (0.1 and 1 microM) or flunarizine (1 microM) significantly reduced glutamate-induced neurotoxicity, the effects being concentration dependent. Lomerizine (1 microM) also exhibited protective effects against both the N-methyl-D-aspartate and kainate induced types of neurotoxicity. However, lomerizine (1 microM) had little effect on the neurotoxicity induced by ionomycin (1 microM) application. Glutamate-induced neurotoxicity was abolished by removing Ca2+ from the medium. These results indicate that lomerizine protects neuronal cells against retinal neurotoxicity both in vivo and in vitro, and that this Ca2+ channel blocker may be useful as a therapeutic drug against retinal diseases that cause neuronal injury, such as normal tension glaucoma (NTG).

Animals↗
PubMed2000

Efficacies of sirolimus (rapamycin) and cyclosporine in allograft vascular disease in non-human primates: trough levels of sirolimus correlate with inhibition of progression of arterial intimal thickening.

We investigated the efficacies of sirolimus (rapamycin) and cyclosporine for inhibition of graft vascular disease (GVD) in cynomolgus monkey recipients of aortic allografts. Increases in arterial intimal thickening in the midgraft (six consecutive cross-sections) after transplantation were quantified by serial intravascular ultrasound (IVUS) from day 21 to day 105. These data enabled correlations between changes in intimal indexes [II = (intimal area/vessel area) x 100] and trough levels of sirolimus and cyclosporine to be determined. Eighteen recipients received no immunosuppression for 6 weeks to allow alloimmune injury to occur. On day 45, monkeys were treated daily with sirolimus (n = 6) or cyclosporine (n = 6); six monkeys remained untreated. II increased significantly from day 63 to day 105 in untreated monkeys and monkeys treated with cyclosporine, whereas monkeys treated with sirolimus did not have a significant increase in II (P = 0.008, P = 0.006, P = NS; paired t-test). The change in II from days 63 to 105 was significantly greater in untreated monkeys compared to sirolimus-treated monkeys (P = 0.13; one-way ANOVA, P = 0.012 Tukey's post hoc test); other post hoc pairwise comparisons were not significant. Mean sirolimus and cyclosporine levels +/- SEM were 43 +/- 7 ng/ml and 562 +/- 20 ng/ml, respectively. Sirolimus trough levels, but not cyclosporine levels, correlated inversely with changes in II from day 42 to 105 (r2 = 0.73, P = 0.03). This non-human primate study shows that inhibition of intimal thickening by sirolimus depends on trough levels and provides the rationale for clinical trials of sirolimus for the control of GVD in organ transplant recipients.

Animals↗
PubMed2000

Identification of a telomeric boundary of the HLA region with potential for predisposition to human narcolepsy.

We report on a study performed to determine a boundary of the region with the potential to contribute to the predisposition to human narcolepsy (the susceptibility region) in the human leukocyte antigen (HLA) region. We investigated a Japanese narcolepsy family, in which a de novo chromosomal recombination occurred between the HLA-DRB1 and HLA-B genes in the proband. The recombinant chromosome carrying HLA-DRB1*1501 was transmitted to the affected child and grandchild, suggesting that a strong genetic factor(s) predisposing to the disorder was (were) present on the chromosome, and that the recombination breakpoint could be regarded as a boundary to the susceptibility region. To search for the breakpoint, we carried out allele typing at various polymorphic sites, e.g., microsatellite repeat polymorphisms, restriction fragment length polymorphisms, and single-nucleotide polymorphisms in the HLA region, and examined haplotypes with the polymorphic sites in the family members. Haplotype analyses revealed that the recombination breakpoint was present approximately 50 kb to the telomeric side of the palmitoyl-protein thioesterase-2 (PPT2) gene in the HLA class III region. From the gene map of the HLA region, the cyclic AMP response element-binding protein-related protein gene (CREB-RP) appeared to be located at the telomeric end in the 50-kb region. Therefore, the data presented here suggest that the susceptibility region for the disorder in the family is present on the centromeric side of the CREB-RP gene in the recombinant Chromosome 6 carrying HLA-DRB1*1501.

Female↗
PubMed2000

Polymerization of guaiacol by lignin-degrading manganese peroxidase from Bjerkandera adusta in aqueous organic solvents.

Lignin-degrading manganese (II) peroxidase (MnP) purified from the culture of a wood-rotting basidiomycete, Bjerkandera adusta, was used in the polymerization of guaiacol. MnP was found to catalyze polymerization of guaiacol in 50% aqueous acetone, dimethyl formamide, methanol, ethanol, dioxane, acetonitrile, ethylene glycol and methylcellosolve. Maximum yield of polyguaiacol was achieved in 50% aqueous acetone. The weight average molecular weight (Mw) of the polymer was estimated to be 30,300 by gel permeation chromatography. However, matrix-assisted laser desorption ionization time of flight mass spectroscopy (MALDI-TOF-MS) analysis gave a more reliable Mw of 1,690. IR, 13C-NMR, MALDI-TOF-MS and pyrolysis GC-MS analyses showed the presence of C-C and C-O linkages and quinone structure in polyguaiacol. It was also indicated that polyguaiacol has a methoxy-phenyl group as the terminal moiety. This suggests that polyguaiacol is a branched polymer in which guaiacol units are cross-linked at the phenolic group. Thermal gravimetric and differential scanning calorimetric analyses were also carried out. MnP also catalyzed the polymerization of o-cresol, 2,6-dimethoxyphenol and other phenolic compounds and aromatic amines. Mw of these polymers ranged from around 1,000 to 1,500.

Basidiomycota↗
PubMed2000

Antibacterial carbohydrate monoesters suppressing cell growth of Streptococcus mutans in the presence of sucrose.

The growth-inhibitory effect of 23 carbohydrate monoesters synthesized by lipases and proteases were assayed to obtain antibacterial agents that suppress the cell growth of Streptococcus mutans. Among the carbohydrate esters synthesized, galactose and fructose laurates showed the highest growth-inhibitory effect, while the other analogs of hexose laurates showed no antibacterial activity, indicating that configuration of the hydroxyl group in carbohydrate moiety markedly affects the antibacterial activity. The cell growth of S. mutans was suppressed by fructose laurates even in the presence of sucrose. Thus, enzymatic synthesis of carbohydrate esters with different core structures has great potential for developing antibacterial agents applicable to food additives.

Alcaligenes↗
PubMed2000

Carboxin resistance transformation of the homobasidiomycete fungus Pleurotus ostreatus.

A novel selection marker gene for transformation of the white-rot basidiomycete Pleurotus ostreatus was developed by introducing a point mutation in a gene which encodes the iron-sulfur protein (Ip) subunit of succinate dehydrogenase. The mutant gene, CbxR, encodes a modified Ip subunit with an amino-acid substitution (His239 to Leu) and confers resistance to the systemic fungicide, carboxin. The DNA sequence was integrated ectopically in the chromosome of the transformants. This is the first report of a homologous marker gene which is available for the molecular breeding of an edible mushroom.

Amino Acid Substitution↗
PubMed2000

Protective effects of ifenprodil against glutamate-induced neurotoxicity in cultured retinal neurons.

PURPOSE: To examine the effects of ifenprodil on glutamate-induced neurotoxicity in cultured retinal neurons. METHODS: Primary cultures obtained from the fetal rat retina (gestation day 17-19) were used for the experiment. Neurotoxicity effects on retinal cultures were quantitatively assessed by the trypan blue exclusion method. The cells were exposed briefly (10 min) to excitatory amino acids (EAA, 1 mM) and then were incubated for 1 h in an EAA-free medium. Ifenprodil (10 mM) was added for the 10-min exposure to EAA and the subsequent 60-min incubation in an EAA-free medium. RESULTS: Ifenprodil dose-dependently prevented cell death induced by glutamate or NMDA, but did not affect that induced by kainate. The protective effects of ifenprodil against glutamate neurotoxicity were significantly reduced by spermidine, a polyamine modulatory site agonist, but not by glycine, a strychnine-insensitive glycine site agonist. CONCLUSION: The findings suggest that ifenprodil protected the cultured retinal cells we used in this study against glutamate neurotoxicity by its inhibitory action on the polyamine modulatory site of the NMDA receptor.

Animals↗
PubMed2000

Superior oblique paresis with contralateral relative afferent pupillary defect.

BACKGROUND: The purpose of this study is to report a case of superior oblique paresis and contralateral relative afferent pupillary defect (RAPD) with normal vision in a patient with brainstem astrocytoma. METHODS: We correlated the patient's clinical findings with anatomical substrates on magnetic resonance imaging (MRI) findings. RESULTS: The patient had right-sided superior oblique paresis. There was a left-sided RAPD, although visual acuities and visual fields were normal in both eyes. T1-weighted, gadolinium-enhanced MRI demonstrated a hyperintense area in the right dorsal midbrain. CONCLUSION: It is suggested that the lesion damaged both the pretectal afferent pupillary pathway and fascicles of the trochlear nerve, causing a unique combination of neuro-ophthalmologic findings.

Adult↗
PubMed2000

The process of closure of experimental retinal holes in rabbit eyes.

BACKGROUND: To investigate the healing process of retinal holes, including the identification of the cell types which play an important role in the process, we created experimental retinal holes with minimal damage to retinal pigment epithelium (RPE) in rabbit eyes. METHODS: Pars plana vitrectomy was performed in the rabbit eye. A dome-shaped retinal detachment (bleb; diameter 1.5 mm) was made by injecting balanced salt solution into the subretinal space, followed by making a retinal hole (diameter 0.5 mm) in the center of the bleb with a silicone-tipped extrusion needle. In one group of rabbits, fluid-air exchange was performed and sulfur hexafluoride gas was injected into the vitreous cavity postoperatively. In another group, gas tamponade was not performed. The operated eyes were examined ophthalmoscopically and enucleated at 1, 4, 7, 14, 30, and 90 days after surgery. Tissues were prepared in 5-microm sections for hematoxylin-eosin staining and immunohistochemistry with antibodies to cytokeratin 18 and glial fibrillary acidic protein (GFAP) and examined by light microscopy. RESULTS: In the gas-injected eyes, the retinal holes were ophthalmoscopically closed by 7 days after the surgery. Microscopic examination revealed that the sensory retina around the retinal hole was reattached, and the area of retinal defect was covered with cells which were positive for cytokeratin 18 and GFAP by 7 days after the surgery. In the eyes without gas tamponade, the retinal holes did not close during the observation period. CONCLUSIONS: These findings suggest that early attachment between the sensory retina and RPE could be essential for closure of a retinal hole, where glial and RPE cells might play an important role. This model seems to be useful to investigate the process of closure of retinal holes.

Animals↗
PubMed2000

Biodegradable scleral implant for intravitreal controlled release of ganciclovir.

BACKGROUND: The aims of this study were to develop biodegradable scleral implants that could overcome previously reported disadvantages such as an adverse burst in the late phase of release and to investigate the release profile of modified scleral implants in vitro and in vivo. METHODS: The modified scleral implants (weight 8.5 mg, length 5 mm) were made of mixtures of poly(DL-lactide) (PLA) with different molecular weights and contained 25 weight % of ganciclovir (GCV). The release of GCV was evaluated in vitro by spectrophotometry. Intravitreal GCV concentrations in vivo were measured by high-performance liquid chromatography following plug implantation in pigmented rabbits. The biocompatibility of the device was determined by indirect ophthalmoscopy and light microscopy. RESULTS: The in vitro release studies showed stable, long-term sustained and slow release. The in vivo release studies showed that the implants had long-term release in the diffusional phase of the triphasic release pattern and only a minor adverse burst of GCV in the late phase. No significant retinal toxicity was observed by histologic examination. CONCLUSION: Our findings showed that this newly modified scleral implant may provide suitable intravitreal drug delivery for treatment of cytomegalovirus retinitis.

Absorbable Implants↗
PubMed2000

Involvement of NMDA-receptor in kainate-induced neurotoxicity in cultured fetal retinal neurons.

BACKGROUND: Both in vivo and in vitro studies suggest that excess stimulation of non-NMDA receptors can result in massive neuronal death in the retina. In particular, murine amacrine neurons have been known to show marked susceptibility to the toxic effects of kainate. PURPOSE: This study was designed to examine and characterize the role of N-methyl-D-aspartate (NMDA) receptor vs non-NMDA receptor in glutamate-induced neurotoxicity in the retina. METHODS: Primary cultures obtained from fetal rat retina (gestation day 16-19) were used for the experiment. The neurotoxicity was assessed quantitatively using the trypan blue exclusion method. Electrophysiological studies using patch-clamp techniques were performed to record whole-cell currents evoked by these excitatory amino acids. RESULTS: Removal of extracellular Ca2+ from the medium or application of MK-801 reduced the extent of cell death induced by the brief exposure to glutamate, NMDA, and kainate. By contrast, cell death induced by a 60-min exposure to kainate was not affected by MK-801. The electrophysiological study demonstrated that MK-801 abolished the whole-cell currents evoked by NMDA but had no effect on those induced by kainate or AMPA. CONCLUSION: These findings demonstrate that brief exposure to kainate induces cell death by way of activating NMDA receptors in cultured fetal retinal neurons and that NMDA receptors are the predominant route of fetal retinal neurotoxicity induced by brief glutamate exposure.

Animals↗
PubMed2000

Hyperinsulinemia during oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients: a serial intravascular ultrasound study.

OBJECTIVES: The purpose of this study was to determine whether hyperinsulinemia during the oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients. BACKGROUND: Although hyperinsulinemia induces increased vascular smooth muscle cell proliferation in experimental models, it has not been determined whether hyperinsulinemia is associated with increased neointimal tissue proliferation after coronary stent implantation. METHODS: Serial (postintervention and six-month follow-up) intravascular ultrasound (IVUS) was used to study 67 lesions treated with Palmaz-Schatz stents in 55 nondiabetic patients. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback, and a neointimal index was calculated as the ratio between the averaged neointimal area and averaged stent area. All patients underwent a 75-g oral glucose tolerance test. Plasma glucose (PG) and immunoreactive insulin (IRI) levels were measured at baseline and 1 and 2 h after the glucose load. The sum of PGs (sigmaPG) and the sum of IRIs (sigmaIRI) were calculated. Body mass index (BMI), lipid levels, and glycosylated hemoglobin levels were measured. RESULTS: There were 27 patients with normal glucose tolerance, and 28 patients with impaired glucose tolerance (IGT). The neointimal index in patients with IGT was greater than that in patients with normal glucose tolerance (42.9 +/- 14% vs. 24.9 +/- 8.3%, respectively, p < 0.0001). Linear regression analysis showed that the neointimal index at follow-up correlated well with sigmaPG (p < 0.0001), fasting IRI (p < 0.0001), sigmaIRI (p < 0.0001), triglyceride level (p = 0.018), and BMI (p < 0.0001). Multiple regression analysis revealed that sigmaIRI (p = 0.0002) and sigmaPG (p = 0.0034) were the best predictors of the greater neointimal index at follow-up. CONCLUSIONS: Serial IVUS assessment shows that hyperinsulinemia during an oral glucose tolerance test is associated with increased neointimal tissue proliferation after coronary stent implantation in nondiabetic patients.

Aged↗
PubMed2000

Secondary glaucoma associated with crystalline lens subluxation.

PURPOSE: To elucidate the clinical characteristics of secondary glaucoma associated with subluxation of the crystalline lens. SETTING: Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, and Department of Ophthalmology, Tenri Hospital, Nara, Japan. METHODS: This retrospective study comprised 14 eyes of 13 patients with uncontrolled intraocular pressure (IOP) and lens subluxation. The subluxated lens was extracted through surgery. RESULTS: Angle closure caused by the subluxated lens was complicated in 3 eyes. In the remaining 11 eyes, uncontrolled IOP elevation was found despite the presence of deep anterior chambers and wide open angles. A mean of 14.1 months +/- 13.7 (SD) after cataract surgery, IOP was well controlled (lower than 21 mm Hg) in all 14 eyes. Mean IOP was 15.4 +/- 2.2 mm Hg at the final examination. Complications included transient vitreous hemorrhage in 5 eyes, choroidal detachment in 2 eyes, and retinal tears in 1 eye. CONCLUSION: Lens extraction surgery was effective in controlling IOP in eyes with secondary glaucoma associated with lens subluxation.

Aged↗
PubMed2000

Site-directed mutagenesis of Asp280 suggests substrate-assisted catalysis of chitinase A1 from Bacillus circulans WL-12.

To study the involvement of Asp280 of chitinase A1 from Bacillus circulans WL-12 in the catalytic reaction of the enzyme, site-directed mutagenesis of this residue was carried out. Kinetic analysis of the mutant chitinases revealed that the residue is not absolutely essential for the catalytic reaction and thus, does not act as the catalytic nucleophile.

Journal Article↗
PubMed2000

Significant association of the tumor necrosis factor receptor 2 (TNFR2) gene with human narcolepsy.

We report on the association study of the tumor necrosis factor receptor 2 (TNFR2) gene with human narcolepsy. A single-nucleotide polymorphism in TNFR2, which is involved in an amino acid substitution [methionine(M)/arginine(R)] at position 196, was investigated in 149 Japanese narcoleptic patients and 204 healthy individuals as controls. Results reveal that the frequency of the TNFR2-196R allele significantly increased in the patients as compared with that in the controls (P=0.029), suggesting that TNFR2 is likely associated with the susceptibility to narcolepsy. In addition, the analyses of the relationship of TNFR2 and TNF-alpha with the susceptibility to narcolepsy indicate the possibility that an additive effect on the susceptibility to the disorder lies between TNFR2-196R and TNF-alpha(-857T) alleles.

Amino Acid Substitution↗