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Biomedical subjects

Hidetoshi Yamashita

Publications and source records attributed to Hidetoshi Yamashita.

At least 19 recordsLinked to original sources
PubMed2006

Development and progression of retinopathy after inpatient management of diabetes.

OBJECTIVE: To examine factors that affect the development of retinopathy after short-term inpatient management of diabetes. PATIENTS AND METHODS: The subjects were 143 patients with type 2 diabetes who were admitted for inpatient management of diabetes, and did not have retinopathy of the right eye at admission, and had an HbA1c level of > or =8.0%. We studied the characteristics of patients who developed retinopathy within one year after discharge. RESULTS: Between the admission date and one year after discharge, twenty-six patients developed retinopathy and the retinopathy subsequently regressed in 5 patients. The 26 patients who developed retinopathy had a significantly longer duration of diabetes (p<0.005), had a higher fasting blood glucose level at admission (p=0.06), and received insulin therapy during the admission at a higher rate (p=0.06) than the 117 patients without retinopathy. The magnitude of the reduction in HbA1c level at 3 months after discharge was smaller in the 13 patients who developed retinopathy within 3 months after discharge than in the 130 patients who did not. Among the 26 patients who developed retinopathy, the HbA1c level at one year after discharge of the 5 patients whose retinopathy regressed was lower than that of the 21 patients whose retinopathy did not regress (p=0.06). CONCLUSIONS: A long duration of diabetes, high fasting blood glucose level at admission, and treatment with insulin were associated with the development of retinopathy. Patients with these characteristics should undergo frequent fundus examinations after correction of hyperglycemia. The retinopathy was likely to improve if patients maintained strict glycemic control after discharge.

Adult↗
PubMed2006

High glucose concentration induces elevated expression of anti-oxidant and proteolytic enzymes in cultured human retinal pigment epithelial cells.

We investigated the differential protein expression patterns of retinal pigment epithelial (RPE) cells exposed to increased glucose concentrations. Cultured human RPE cells (ARPE-19) were exposed for 4 days with normal blood glucose concentration (5.5 mM D-glucose), followed by exposure to either normal (5.5 mM) or high (33 mM) concentrations of D-glucose for 48h. Protein extracts of glucose-treated RPE cells were then subjected to comparative proteome analysis based on 2-D gel electrophoresis. Protein spots were visualized by silver staining. The differentially expressed proteins were excised and digested in-gel with trypsin, then analysed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The expression levels of cathepsin B, glutathione peroxidase and heat shock protein 27 were increased, and that of protein disulfide isomerase decreased in high glucose treated RPE compared to normal glucose. The isoelectric point of copper/zinc-containing superoxide dismutase (Cu/Zn-SOD) shifted toward acidic region in response to high glucose. Cu/Zn-SOD activity in high glucose group was significantly lower than that in normal glucose group (P<0.05, Mann-Whitney U-test). Systematic survey of protein expression has revealed that RPE cells respond to acute, pathologically high glucose levels by the elevated expression of anti-oxidant and proteolytic enzymes.

Antioxidants↗
PubMed2006

Vitreous levels of pigment epithelium-derived factor and vascular endothelial growth factor are related to diabetic macular edema.

PURPOSE: To investigate whether vitreous levels of vascular endothelial growth factor (VEGF) and pigment epithelium-derived factor (PEDF) are related to diabetic macular edema (DME). DESIGN: Retrospective case-control study. PARTICIPANTS: Thirty-six patients with DME, 6 diabetic patients without retinopathy, and 13 patients with nondiabetic ocular disease. METHODS: After vitreous fluid samples were obtained at vitreoretinal surgery, VEGF and PEDF levels in the vitreous fluid were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Correlations between vascular permeability and the vitreous fluid levels of VEGF and PEDF. RESULTS: The vitreous level of VEGF was significantly higher in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively). Conversely, the vitreous level of PEDF was significantly lower in patients with DME than in nondiabetic patients and diabetic patients without retinopathy (P<0.0001 and P<0.0001, respectively). The vitreous level of PEDF did not correlate significantly with that of VEGF (P = 0.1806). The vitreous level of VEGF was significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0022). Conversely, the vitreous PEDF level was significantly lower in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0172). Vitreous levels of VEGF and PEDF were related to the retinal thickness at the central fovea (P<0.0001 and P = 0.0469, respectively). CONCLUSIONS: Our retrospective study suggests that VEGF and PEDF have an independent association with vascular permeability in the eye and on the DME, and we recommend that prospective validation of our findings be undertaken to confirm these observations.

Capillary Permeability↗
PubMed2006

Cardiovascular risk factors and retinal microvascular signs in an adult Japanese population: the Funagata Study.

OBJECTIVE: To describe the prevalence of retinal vascular signs and their association with cardiovascular risk factors in a Japanese population. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Adult persons aged 35 years or older from Funagata, Yamagata Prefecture, Japan (n = 1481). METHODS: The Funagata Study is a Japanese population-based study of persons aged 35 years or older, and included 1961 nondiabetic participants (53.3% of 3676 eligible subjects). A nonmydriatic retinal photograph was taken of 1 eye to assess retinal microvascular signs. Retinal arteriolar wall signs (focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex) and retinopathy were assessed in 1481 participants without diabetes (40.3% of eligible persons) using a standardized protocol. Using a computer-assisted method, retinal vessel diameters were measured in 921 participants with gradable retinal image (25.1% of eligible persons). MAIN OUTCOME MEASURES: Prevalence of retinal microvascular signs and their association with cardiovascular risk factors. RESULTS: Moderate or severe focal arteriolar narrowing, arteriovenous nicking, enhanced arteriolar wall reflex, and retinopathy were found in 8.3%, 15.2%, 18.7%, and 9.0%, respectively, of the study population. Mean (+/-standard error) values for retinal arteriolar diameter were 178.6+/-21.0 mum, and mean values (+/-standard error) for venular diameter were 214.9+/-20.6 mum. Older persons were more likely to have retinal arteriolar wall signs, retinopathy, and narrower retinal vessel diameters. After adjusting for multiple factors, each 10-mmHg increase in mean arterial blood pressure was associated with a 20% to 40% increased likelihood of retinal arteriolar signs and a 2.8-mum reduction in arteriolar diameter. Retinopathy was associated with higher body mass index and both impaired glucose tolerance and impaired fasting glucose. CONCLUSIONS: In nondiabetic Japanese adults, retinal arteriolar wall signs were associated with older age and increased blood pressure, whereas retinopathy was associated with older age, higher body mass index, impaired glucose tolerance, and impaired fasting glucose. These findings are comparable with data from white populations.

Adult↗
PubMed2006

Vitreous fluid biomarkers.

Interactions between cells and the network of secreted proteins are associated with the ocular disease. In most cases, clinical appearcance is sufficiently diagnostic. However, in cases of nonspecific or atypical clinical presentation, diagnostic sampling of vitreous fluid can aid diagnosis and treatment for ocular disease. Progresses in the basic sciences, particularly molecular biology, and advances in surgical instrumentation have greatly enhanced the diagnostic armamentarium. These developments also have led to a better understanding of the pathophysiological processes involved in ocular diseases and have prompted evolution of new therapeutic modalities. In this chapter, we review techniques for vitreous fluid sampling and biomarker quantitation thereof. The molecular biology of bioactive vitreous fluid factors is also discussed with respect to their clinical involvement in the development of ocular disease.

Biomarkers↗
PubMed2005

Intravitreal levels of vascular endothelial growth factor and interleukin-6 are correlated with macular edema in branch retinal vein occlusion.

BACKGROUND: To investigate whether vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contributes to the pathogenesis of macular edema in eyes with branch retinal vein occlusion (BRVO), the correlations between these factors were investigated. METHODS: We studied 25 patients suffering from macular edema with BRVO and 14 patients with nonischemic ocular disease (control group). The degree of retinal ischemia was evaluated in terms of the area of capillary nonperfusion using Scion Images, and the severity of macular edema was examined using optical coherence tomography. Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and VEGF and IL-6 levels in the vitreous fluid and plasma were determined by means of enzyme-linked immunosorbent assays. RESULTS: Vitreous fluid levels of VEGF and IL-6 were significantly elevated in patients with BRVO compared with control patients (P = 0.0011 and P < 0.0001, respectively). Also, the vitreous level of VEGF was significantly correlated with that of IL-6 (P = 0.0012), and vitreous levels of VEGF and IL-6 were correlated with the size of the BRVO nonperfusion area (P < 0.0001 and P = 0.0033, respectively). Furthermore, vitreous levels of VEGF and IL-6 were correlated with the severity of macular edema (P = 0.0008 and P = 0.0191, respectively) and the severity of macular edema of BRVO was significantly correlated with the size of the BRVO nonperfusion area (P=0.0044). CONCLUSIONS: The levels of VEGF and IL-6 are increased in patients with macular edema with BRVO and are significantly correlated with the size of the nonperfusion area and the severity of macular edema. Therefore, they may play a role in macular edema with BRVO.

Enzyme-Linked Immunosorbent Assay↗
PubMed2005

Neuroprotective effects of erythropoietin on glutamate and nitric oxide toxicity in primary cultured retinal ganglion cells.

Erythropoietin receptor (EpoR) is expressed in the central nervous system (CNS), however, no clear consensus has been obtained whether Epo acts as a prosurvival factor in neurons. Because retinal ganglion cell (RGC) death is a common cause of reduced visual function in several ocular diseases, we explored whether Epo might potentially be beneficial in protecting RGCs from glutamate and nitric oxide (NO)-induced cytotoxicity, using isolated RGCs by a two-step panning method. Brain-derived neurotrophic factor (BDNF) was used as a positive control. EpoR mRNA was expressed in isolated RGCs, and EpoR protein was expressed on the RGCs in the normal and ischemic retinas. Epo had less potential to improve the survival of primary RGCs in serum-free medium than BDNF. In these cells, BDNF, but not Epo, downregulated the expression of Bim, a proapoptotic Bcl-2 family member that plays a key role in cytokine-mediated cell survival, suggesting a possible mechanism for this difference. When RGCs were cultured with glutamate or an NO-generating reagent, the survival of RGCs was compromised, and Bcl-2 expression was decreased in these cells. Both Epo and BDNF significantly reduced RGC death induced by glutamate and NO. In agreement with this, these factors reversed the Bcl-2 expression. These findings suggest that Epo may be a potent neuroprotective therapeutic agent for the treatment of ocular diseases that are characterized by RGC death.

Animals↗
PubMed2005

Hyaluronan fragments induce endothelial cell differentiation in a CD44- and CXCL1/GRO1-dependent manner.

Hyaluronan is a glycosaminoglycan of the extracellular matrix. In tumors and during chronic inflammatory diseases, hyaluronan is degraded to smaller fragments, which are known to stimulate endothelial cell differentiation. In this study, we have compared the molecular mechanisms through which hyaluronan dodecasaccharides (HA12), and the known angiogenic factor, fibroblast growth factor 2 (FGF-2), induce capillary endothelial cell sprouting in a three-dimensional collagen gel. The gene expression profiles of unstimulated and HA12- or FGF-2-stimulated endothelial cells were compared using a microarray analysis approach. The data revealed that both FGF-2 and HA12 promoted endothelial cell morphogenesis in a process depending on the expression of ornithine decarboxylase (Odc) and ornithine decarboxylase antizyme inhibitor (Oazi) genes. Among the genes selectively up-regulated in response to HA12 was the chemokine CXCL1/GRO1 gene. The notion that the induction of CXCL1/GRO1 is of importance for HA12-induced endothelial cell sprouting was supported by the fact that morphogenesis was inhibited by antibodies specifically neutralizing the CXCL1/GRO1 protein product. HA12-stimulated endothelial cell differentiation was exerted via binding to CD44 since it was inhibited by antibodies blocking CD44 function. Our data show that hyaluronan fragments and FGF-2 affect endothelial cell morphogenesis by the induction of overlapping but also by distinct sets of genes.

Animals↗
PubMed2005

Pathogenesis of macular edema with branch retinal vein occlusion and intraocular levels of vascular endothelial growth factor and interleukin-6.

PURPOSE: To determine whether correlations between vascular endothelial growth factor (VEGF) or interleukin-6 (IL-6) contribute to the pathogenesis of macular edema in eyes of patients with branch retinal vein occlusion (BRVO). DESIGN: Retrospective case-control study. METHODS: Nineteen patients with macular edema with BRVO and seven patients with non-ischemic ocular disease (control group) were studied. The degree of retinal ischemia was evaluated in terms of the area of capillary non-perfusion, and the severity of macular edema was examined by optical coherence tomography. Aqueous humor samples were obtained at the time of combined vitrectomy and cataract surgery, and VEGF and IL-6 levels in aqueous humor and plasma were determined by enzyme-linked immunosorbent assay. RESULTS: Aqueous levels of VEGF (351 +/- 273 pg/ml) and IL-6 (7.10 +/- 6.51 pg/ml) were significantly elevated in patients with BRVO compared with the control patients (119 +/- 38.7 pg/ml and 2.27 +/- 1.11 pg/ml, respectively) (P = .0017 and P = .0052, respectively). Aqueous level of VEGF was significantly correlated with that of IL-6 (P = .0396), and aqueous levels of VEGF and IL-6 were correlated with the size of the BRVO non-perfused area (P < .0001 and P = .0331, respectively). Aqueous level of VEGF was correlated with the severity of macular edema (P = .0306). CONCLUSIONS: VEGF and IL-6 may be involved in the pathogenesis of macular edema with BRVO. The increase in these cytokines might be used as a unique index of BRVO, through which we can determine the severity of the ischemic condition as being in a quiescent state or an exacerbation of macular edema.

Aged↗
PubMed2005

Vitreous levels of vascular endothelial growth factor and intercellular adhesion molecule 1 are related to diabetic macular edema.

PURPOSE: To investigate whether vascular endothelial growth factor (VEGF) or soluble intercellular adhesion molecule 1 (sICAM-1) is related to diabetic macular edema (DME). DESIGN: Retrospective case-control study. PARTICIPANTS: Thirty-three patients who had DME and 13 patients with nondiabetic ocular disease (control group). METHODS: Vitreous fluid samples were obtained at the time of vitreoretinal surgery, and the VEGF and sICAM-1 levels in vitreous fluid and plasma were measured by enzyme-linked immunosorbent assay. MAIN OUTCOME MEASURES: Relationship between vitreous levels of VEGF or sICAM-1 and DME. RESULTS: Vitreous levels of VEGF and sICAM-1 were significantly higher in DME patients than in control patients (P < 0.0001 and P = 0.0004, respectively). The vitreous level of VEGF was significantly correlated with that of sICAM-1 (P < 0.0001). Vitreous levels of both VEGF and sICAM-1 were significantly higher in patients with hyperfluorescent DME than in those with minimally fluorescent DME (P = 0.0027 and P = 0.0005, respectively). The vitreous levels of both VEGF and sICAM-1 were significantly correlated with retinal thickness at the central fovea (P < 0.0001 and P = 0.0005, respectively) CONCLUSIONS: We found that both VEGF and sICAM-1 were elevated in the vitreous fluid of patients with hyperfluorescent DME. These results suggest that VEGF and ICAM-1 are related to the increase of vascular permeability in DME patients.

Blood-Retinal Barrier↗
PubMed2004

Aqueous humor levels of cytokines are related to vitreous levels and progression of diabetic retinopathy in diabetic patients.

BACKGROUND: Cytokine levels are elevated in the ocular fluid of diabetic patients. It is unclear whether aqueous humor levels of vascular endothelial growth factor (VEGF) and interleukin-6 (IL-6) are related to the vitreous fluid levels of these substances and to the progression of diabetic retinopathy. METHODS: Aqueous humor and vitreous fluid samples were obtained during cataract and vitreous surgery from ten eyes of ten patients with diabetic macular edema and 26 eyes of 26 patients with proliferative diabetic retinopathy (PDR). The VEGF and IL-6 levels in aqueous humor, vitreous fluid, and plasma were measured by enzyme-linked immunosorbent assay. RESULTS: VEGF and IL-6 levels in aqueous humor were significantly correlated with those in vitreous fluid (rho=0.793 and rho=0.737, respectively). VEGF levels in aqueous humor and vitreous fluid were significantly correlated with the corresponding IL-6 levels (rho=0.631 and rho=0.687, respectively). The aqueous and vitreous levels of VEGF were significantly correlated with the severity of diabetic retinopathy (rho=0.659 and rho=0.771, respectively). Aqueous and vitreous levels of IL-6 were also significantly correlated with the severity of diabetic retinopathy (rho=0.742 and rho=0.746, respectively). Aqueous and vitreous levels of both VEGF and IL-6 were significantly higher in the patients with active PDR than those in quiescent PDR. CONCLUSIONS: Our results suggest that there is a significant relationship between VEGF and IL-6 levels in aqueous humor and in vitreous fluid. Measurement of the aqueous levels of VEGF and IL-6 may be useful to analyze the pathogenesis of diabetic retinopathy and to predict disease activity.

Aqueous Humor↗
PubMed2004

The genome sequence of silkworm, Bombyx mori.

We performed threefold shotgun sequencing of the silkworm (Bombyx mori) genome to obtain a draft sequence and establish a basic resource for comprehensive genome analysis. By using the newly developed RAMEN assembler, the sequence data derived from whole-genome shotgun (WGS) sequencing were assembled into 49,345 scaffolds that span a total length of 514 Mb including gaps and 387 Mb without gaps. Because the genome size of the silkworm is estimated to be 530 Mb, almost 97% of the genome has been organized in scaffolds, of which 75% has been sequenced. By carrying out a BLAST search for 50 characteristic Bombyx genes and 11,202 non-redundant expressed sequence tags (ESTs) in a Bombyx EST database against the WGS sequence data, we evaluated the validity of the sequence for elucidating the majority of silkworm genes. Analysis of the WGS data revealed that the silkworm genome contains many repetitive sequences with an average length of <500 bp. These repetitive sequences appear to have been derived from truncated transposons, which are interspersed at 2.5- to 3-kb intervals throughout the genome. This pattern suggests that silkworm may have an active mechanism that promotes removal of transposons from the genome. We also found evidence for insertions of mitochondrial DNA fragments at 9 sites. A search for Bombyx orthologs to Drosophila genes controlling sex determination in the WGS data revealed 11 Bombyx genes and suggested that the sex-determining systems differ profoundly between the two species.

Animals↗