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T Ishibashi

Publications and source records attributed to T Ishibashi.

At least 19 recordsLinked to original sources
PubMed2006

Analysis of corneal inflammation induced by cauterisation in CCR2 and MCP-1 knockout mice.

AIM: To elucidate the role of CCR2/MCP-1 in corneal inflammation. METHODS: A cauterisation induced corneal inflammation model was used. The corneas were cauterised with silver nitrate in CCR2 knockout (KO) mice, MCP-1 KO mice, and control mice. Clinical signs such as corneal oedema and opacity were examined 96 hours after cauterisation and the phenotypes of the cells infiltrating the cornea were analysed by flow cytometry. Corneal inflammation in neutrophil depleted mice was also analysed. RESULTS: After cauterisation both CCR2 KO and MCP-1 KO mice showed the same levels of corneal oedema and opacity as control mice. Flow cytometry revealed that in control mice most of the infiltrating cells were neutrophils and macrophages, whereas in both CCR2 KO mice and MCP-1 KO mice, the number of macrophages infiltrating the cornea were markedly reduced. However, prominent infiltrates of neutrophils were still observed in the cornea in CCR2 KO mice and MCP-1 KO mice. The depletion of neutrophils significantly reduced the oedema and opacity induced in the cornea by cauterisation. CONCLUSION: The CCR2 and MCP-1 molecules are not essential for cauterisation induced corneal inflammation. Neutrophils, rather than migrated macrophages, are the final effector cells involved in inducing inflammation in this model.

Animals↗
PubMed2006

Double aortic arch with atresia, tapering and aneurysm of the left arch.

An adult male underwent chest radiography for a health check-up. This disclosed both thoracic vascular anomalies and a small nodular shadow in the left side of the superior mediastinum. Axial MRI and three-dimensional volume-rendering MR angiography revealed both a double aortic arch with left atretic arch proximal to the left common carotid artery (subtype 4), and also tapering and aneurysm of the left arch distal to the left subclavian artery. To the authors' knowledge, this report describes the first case of subtype 4 of atretic double arch with left arch atresia. Such thoracic vascular anomalies have been a theoretical possibility, but no cases have been reported to date.

Adult↗
PubMed2005

3 dB squeezing by single-pass parametric amplification in a periodically poled KTiOPO4 crystal.

We present the experimental observation of pulsed squeezed light from a degenerate optical parametric amplifier pumped by a second harmonic of a continuous-wave mode-locked Nd:YVO4 laser. With a single pass through a 10 mm long periodically poled KTiOPO4 crystal, the classical parametric gain of 11 is observed. The measured noise reduction in the quiet quadrature is 3.2 dB below the shot-noise level.

Journal Article↗
PubMed2005

Novel mutation in ABCC6 gene in a Japanese pedigree with pseudoxanthoma elasticum and retinitis pigmentosa.

PURPOSE: To report a novel mutation of the ABCC6 gene in a Japanese family that had a case of pseudoxanthoma elasticum (PXE) another with PXE and retinitis pigmentosa. METHODS: Ophthalmologic examinations were performed, and the ABCC6 gene was analysed by direct genomic sequencing. RESULTS: Fundus examinations of the 48-year-old proband disclosed angioid streaks and a peud'orange appearance of the retina of the both eyes, whereas both of his 25- and 20-year-old daughters had pigmentary degeneration and angioid streaks. In the sibilings, the mixed cone-rod ERG was almost nondetectable, whereas that of the proband was well-preserved. Molecular genetic analysis revealed that the proband has a homozygous nonsense mutation at the 595 bp in the ABCC6, and the siblings were heterozygous for the same mutation. This mutation was not detected in Japanese subjects in the JSNP database (http://snp.ims.u-tokyo.ac.jp/). CONCLUSIONS: Our results demonstrated an association between a novel mutation in the ABCC6 gene and PXE in a Japanese family.

Adult↗
PubMed2005

The characterisation of hyalocytes: the origin, phenotype, and turnover.

AIM: To determine the characterisation of hyalocytes: the origin, phenotype, and turnover in the rodent. METHODS: To characterise the ultrastructure and distribution of hyalocytes, transmission and scanning electron microscopy was performed in rat eyes. Immunophenotypical analysis was performed by either anti-ED1 or ED2 antibodies. To examine the origin of the hyalocytes, the chimeric mice were created and were used to transplant the bone marrow (BM) cells from enhanced green fluorescent protein (EGFP) transgenic mice. The turnover of hyalocytes was examined at 0, 4, 6, 7, and 12 months after BM transplantation. RESULTS: Hyalocytes were distributed especially in the vitreous cortex and had an irregular shape with a spherical granule. Immunophenotypical studies demonstrated that most of the hyalocytes in rat eyes expressed ED2 but not ED1. In the chimeric mice, the hyalocytes were GFP negative right after BM transplantation. Interestingly, more than 60% of hyalocytes were replaced within 4 months and approximately 90% within 7 months after BM transplantation. CONCLUSIONS: The rodent hyalocytes were shown to express tissue macrophage marker, were derived from BM, and totally replaced within 7 months. These data provide the characterisation of hyalocytes in physiological conditions, especially their origin, distribution, and turnover, and may contribute to the better understanding of the pathogenesis of vitreoretinal disease.

Animals↗
PubMed2004

Comparison of diagnostic methods for diabetes mellitus based on prevalence of retinopathy in a Japanese population: the Hisayama Study.

AIMS/HYPOTHESIS: The aims of this study were to compare the ability of tests measuring fasting plasma glucose, 2-h plasma glucose and HbA1c levels in predicting specific diabetic retinopathy, and to determine the cut-off level of each measurement for diagnosing diabetes in a Japanese population. METHODS: In a total of 1637 subjects, fasting plasma glucose, 2-h plasma glucose and HbA1c levels were measured in a 75-g oral glucose tolerance test, and diabetic retinopathy was assessed by ophthalmic examination. We calculated receiver operating characteristic (ROC) curves as well as the prevalence of diabetic retinopathy by deciles of the distribution of these glycaemic measurements. RESULTS: Of the subjects, 37 (2.3%) had diabetic retinopathy. The prevalence of retinopathy dramatically increased in the tenth decile of each variable. Analysis with ROC curves showed that the optimal cut-off levels for diagnosis of diabetes were 6.4 mmol/l for fasting plasma glucose, 11.1 mmol/l for 2-h plasma glucose, and 5.7% for HbA1c. The sensitivities for the cut-off point of the three measurements were identical (86.5%), and the specificities were similar (fasting plasma glucose 87.3%; 2-h plasma glucose 89.6%; HbA1c 90.1%). The area under the ROC curve for 2-h plasma glucose (96.1%) was slightly but not significantly larger than that for fasting plasma glucose (90.0%) and that for HbA1c (94.5%). CONCLUSIONS/INTERPRETATION: . Our findings suggest that measuring fasting plasma glucose or HbA1c is just as useful as measuring 2-h plasma glucose for the diagnosis of diabetes, and that the cut-off point for diagnostic fasting plasma glucose level is lower than that of the current diagnostic criteria.

Blood Glucose↗
PubMed2004

Cetirizine, an H1-receptor antagonist, suppresses the expression of macrophage migration inhibitory factor: its potential anti-inflammatory action.

BACKGROUND: H1-receptor antagonists are often effective in the treatment of allergic disorders such as atopic dermatitis. Cetirizine, a putative H1-receptor antagonist, has recently been shown to have anti-inflammatory properties through the inhibition of leucocyte recruitment and activation, and by the reduction of ICAM-1 expression on keratinocytes. OBJECTIVE: To further elucidate the anti-inflammatory properties of cetirizine, we first examined its effects on antigen-induced eosinophilia and neutrophila in vivo. We then examined the anti-inflammatory effects of cetirizine on a human keratinocyte A431cell line. METHODS: Mice were sensitized subcutaneously with ragweed pollen and were challenged intraperitoneally with the allergen. Cetirizine diluted in sterile water (0-20 mg/kg) or only sterile water was administered orally. Peritoneal cells were obtained at 8 and 24 h after challenge. The eosinophilia and neutrophilia induced by ragweed pollen extract were quantitated. Macrophage migration inhibitory factor (MIF), macrophage inflammatory protein 2 (MIP-2) and eotaxin contents of peritoneal fluid were also measured by mouse ELISA. The effects of cetirizine on MIF-induced IL-8 production in A431 cells were examined by ELISA. The effects of cetirizine on MIF expression and production in A431 cells were examined by human MIF ELISA and Northern blot analysis. RESULTS: Eosinophilia and neutrophilia induced by ragweed pollen extract were found to be significantly reduced in cetirizine-treated mice (20 mg/kg). MIF, a pleuripotent cytokine, was significantly decreased at 8 and 24 h in the peritoneal fluid by cetirizine treatment. MIP-2 and eotaxin were also decreased 8 and 24 h, respectively, after challenge in the peritoneal fluid with cetirizine treatment. MIF stimulates IL-8 production in A431 cells. We found that MIF production in A431 cells was inhibited by 10 microm cetirizine. Consistent with this, cetirizine significantly inhibited MIF-induced IL-8 production. CONCLUSION: These results suggest that cetirizine exerts its anti-inflammatory effects by inhibiting MIF as well as IL-8 production, such as those involved in inflammatory allergic skin disease, suggesting a broad spectrum of action beyond its mere H1-receptor-antagonistic function.

Allergens↗
PubMed2004

The relative contributions of each subset of ocular infiltrated cells in experimental choroidal neovascularisation.

AIM: Choroidal neovascularisation (CNV) is a major cause of blindness in adults. The aim of this study was to investigate the role of infiltrating cells in the development of experimental CNV. METHODS: CNV was induced in C57BL/6 (B6) mice by laser photocoagulation (PC). After PC, the numbers of each subset of infiltrated cells were analysed by flow cytometry at multiple time points. Each subset (except for macrophages) was depleted by the specific antibodies in vivo. Thereafter, the area of CNV was compared between the control B6 mice and the specific antibody treated mice 7 days after PC. The CNV formation in neutrophil depleted CC chemokine receptor-2 (CCR2) knockout mice was also examined to minimise the effects of macrophages. RESULTS: In the early phase of CNV formation, a large number of neutrophils and macrophages infiltrated to the eyes. Natural killer (NK) cells and T lymphocytes were barely detected while no B lymphocytes were detected. The CNV areas did not significantly change compared between the control B6 mice and the specific antibody treated mice. However, the neutrophil depleted CCR2KO mice resulted in a reduction of CNV. CONCLUSION: Although lymphocytes and NK cells had little effect on CNV formation, neutrophils partially contributed to CNV in the absence of macrophages.

Animals↗
PubMed2003

In situ photoemission study of the room temperature ferromagnet ZnGeP2:Mn.

The chemical states of the ZnGeP(2):Mn interface which shows ferromagnetism above room temperature have been studied by photoemission spectroscopy. Mn deposition on the ZnGeP2 substrate heated to 400 degrees C induced Mn substitution for Zn and then the formation of metallic Mn-Ge-P compounds. Depth profile studies have shown that Mn 3d electrons changed their character from itinerant to localized along the depth, and in the deep region, dilute divalent Mn species (<5% Mn) was observed with a coexisting metallic Fermi edge of non-Mn 3d character. The possibility of hole doping through Mn substitution for Ge and/or Zn vacancy is discussed.

Journal Article↗
PubMed2003

Simian immunodeficiency virus-based lentivirus vector for retinal gene transfer: a preclinical safety study in adult rats.

Although lentivirus vectors hold promise for ocular gene therapy, they also have potential safety issues, particularly in the case of the current human immunodeficiency virus-based vectors. We recently developed a novel lentivirus vector derived from the nonpathogenic simian immunodeficiency virus from African green monkeys (SIVagm) to minimize these potentials. In this preclinical study, we evaluated whether SIV vector could be efficiently and safely applicable to retinal gene transfer by assessing the transgene expression, retinal function and histology over a 1-year period following subretinal injection in adult rats. The functional assessment via electroretinogram after both titers of SIV-lacZ (2.5 x 10(7) or 2.5 x 10(8) transducing units/ml) injection revealed both the dark and light adaptations to soon be impaired, in a dose-dependent manner, after a buffer injection as well, and all of them recovered to the control range by day 30. In both titers tested, the retinas demonstrated a frequent transgene expression mainly in the retinal pigment epithelium; however, the other retinal cells rarely expressed the transgene. Retinas exposed to a low titer virus showed no significant inflammatory reaction throughout the observation period, and also maintained the transgene expression over a 1-year period. In the retinas exposed to a high titer virus, however, mononuclear cell infiltration persisted in the subretinal area, and the retina that corresponded to the injected area finally underwent degeneration by around day 90. No retinal neoplastic lesions could be found in any animals over the 1-year period. We thus propose that SIV-mediated stable gene transfer might be useful for ocular gene transfer; however, more attention should be paid to avoiding complications when administering high titer lentivirus to the retina.

Animals↗
PubMed2003

Simian lentiviral vector-mediated retinal gene transfer of pigment epithelium-derived factor protects retinal degeneration and electrical defect in Royal College of Surgeons rats.

Retinitis pigmentosa (RP) is a heterogenous group of inherited retinal diseases resulting in adult blindness caused by mutations of various genes. Although it is difficult to cure the blindness that results from these diseases, delaying the disease progression may be of great benefit, since the majority of RP diseases are seen in middle age or later. To test a gene therapy strategy for RP using a neurotrophic factor gene, we assessed the effect of simian lentivirus (SIV)-mediated subretinal gene transfer of pigment epithelium-derived factor (PEDF), a potent neurotrophic factor, during the disease progression in Royal College of Surgeons (RCS) rats, a well-accepted animal model of RP. Regional gene transfer via SIV into the peripheral subretinal space at the nasal hemisphere was performed in all animals to monitor site-specific transgene expression as well as the therapeutic effect in each retina. Gene transfer of lacZ and PEDF was observed in the regional pigment epithelium corresponding to the regional gene transfer. Histologically, PEDF gene transfer significantly protected the loss of photoreceptor cells (PCs) corresponding to the regions of the gene transfer, compared to those of control groups during the course of the experiment. The antiapoptotic effect of PEDF on PCs is likely to be a related mechanism, because a significant reduction of terminal dUTP-nicked end labeling-positive PC numbers was found in PEDF-treated eyes compared to those of the control group (P<0.05). PEDF-treated eyes also retained a significant sensitivity to light flash during the experimental course. These findings clearly show that neuroprotective gene therapy using PEDF can protect retinal degeneration and functional defects in individuals with RP.

Animals↗
PubMed2003

Risk factors for age related maculopathy in a Japanese population: the Hisayama study.

AIMS: To examine the risk factors for age related maculopathy (ARM) in a sample Japanese population. METHODS: In 1998, a cross sectional community survey was conducted among residents of Hisayama. A total of 596 men and 886 women living in Hisayama, Japan, aged 50 years or older consented to participate in the study. Each participant underwent a comprehensive examination that included an ophthalmic examination. The presence of ARM was determined by grading from fundus examination by indirect ophthalmoscopy, slit lamp examination, and colour fundus photographs. Using these cross sectional data, logistic regression analyses were performed to determine the risk factors for ARM. The following 10 possible risk factors were used: age, cataract, hypertension (history), hypertension (history or examination), diabetes, hyperlipidaemia, current smoker, alcohol intake, BMI, and WBC. RESULTS: ARM was detected in 19.5% of men and 14.9% of women. Men were found to have a significantly higher prevalence of ARM than women. Multiple logistic regression analysis showed that age and hypertension (history or examination) were significantly associated with ARM in men, whereas only age was a significant risk factor for ARM in women. CONCLUSIONS: This study suggests that higher age and male sex are relevant risk factors for ARM in Japan. In addition, hypertension is a relevant risk factor in men.

Age Distribution↗
PubMed2003

Pars plana vitrectomy assisted by triamcinolone acetonide for refractory uveitis: a case series study.

AIM: To examine the outcome of a triamcinolone acetonide (TA) assisted pars plana vitrectomy (PPV) for refractory uveitis. METHODS: Six patients suffering from proliferative vitreoretinopathy (PVR) with refractory uveitis underwent a TA assisted PPV. The patients consisted of one with Vogt-Koyanagi-Harada disease, one with acute retinal necrosis, one with Behçet's disease, and three with sarcoidosis. TA was inoculated into the vitreous cavity to visualise the vitreous. In four of six patients, 4 mg of TA were intentionally left in the vitreous cavity to reduce the degree of postoperative inflammation. RESULTS: The vitreous body was clearly seen using TA during surgery, which greatly helped us to perform a posterior hyaloid resection safely and thoroughly. As we previously observed in other disease, TA allowed us to visualise the transparent vitreous and thus was helpful in removing the vitreous cortex from the retina completely in uveitis. One patient (Behçet's disease, in whom TA was intentionally left) showed an elevated intraocular pressure (IOP) transiently after surgery which was controllable by topical eye drops. The remaining TA diminished day by day and had almost completely disappeared within a month from operation. CONCLUSION: TA improved the visibility of the hyaloid and the safety of the surgical procedures and no serious complications were observed after TA assisted PPV in uveitis. Although the long term effects are still unknown, this method appears to be potentially useful as an improved treatment for PVR associated with refractory uveitis.

Adult↗
PubMed2003

Demonstration of glucose-6-phosphate dehydrogenase in rat Kupffer cells by a newly-developed ultrastructural enzyme-cytochemistry.

Although various tissue macrophages possess high glucose-6-phosphate dehydrogenase (G6PD) activity, which is reported to be closely associated with their phagocytotic/bactericidal function, the fine subcellular localization of this enzyme in liver resident macrophages (Kupffer cells) has not been determined. We have investigated the subcellular localization of G6PD in Kupffer cells in rat liver, using a newly developed enzyme-cytochemical (copper-ferrocyanide) method. Electron-dense precipitates indicating G6PD activity were clearly visible in the cytoplasm and on the cytosolic side of the endoplasmic reticulum of Kupffer cells. Cytochemical controls ensured specific detection of the enzymatic activity. Rat Kupffer cells abundantly possessed enzyme-cytochemically detectable G6PD activity. Kupffer cell G6PD may play a role in liver defense by delivering NADPH to NADPH-dependent enzymes. G6PD enzyme-cytochemistry may be a useful tool for the study of Kupffer cell functions.

Animals↗
PubMed2002

A formula for predicting optimal dosage of nedaplatin based on renal function in adult cancer patients.

PURPOSE: To predict the optimal dosage for nedaplatin ( cis-diammineglycolatoplatinum), an anticancer drug and a platinum derivative like cisplatin and carboplatin, a simple formula was developed based on renal function in Japanese adult cancer patients. PATIENTS AND METHODS: Unbound platinum concentrations in plasma after intravenous infusion of nedaplatin were measured for 187 courses in 145 patients with lung, esophageal, and cervical and ovarian cancer undergoing clinical treatment. The data were divided into two sets, a model development data set of 94 courses and a validation data set of 93 courses. Regression analysis was applied to the relationship between the unbound platinum clearance (CL) of nedaplatin and the patients' renal function. The predictability and usefulness of this formula were assessed by validation using the external data set of 93 courses obtained from 75 patients. RESULTS: A simple formula was obtained for predicting the platinum clearance using the creatinine clearance (CLcr): CL=0.0836xCLcr+3.45. Indices for the predictive performance for CL and the area under the plasma concentration curve (AUC) in the validation data were almost the same as those for the model development data. CONCLUSIONS: A formula for predicting the CL of unbound platinum after nedaplatin administration was developed, and only CLcr was found to be a significant covariate of the CL. This formula was useful for estimating the CL for the second as well as the first treatment with nedaplatin.

Adult↗