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Biomedical subjects

Daisuke Watanabe

Publications and source records attributed to Daisuke Watanabe.

At least 37 records · Page 2Linked to original sources
PubMed2005

Erythropoietin as a retinal angiogenic factor in proliferative diabetic retinopathy.

BACKGROUND: Although vascular endothelial growth factor (VEGF) is a primary mediator of retinal angiogenesis, VEGF inhibition alone is insufficient to prevent retinal neovascularization. Hence, it is postulated that there are other potent ischemia-induced angiogenic factors. Erythropoietin possesses angiogenic activity, but its potential role in ocular angiogenesis is not established. METHODS: We measured both erythropoietin and VEGF levels in the vitreous fluid of 144 patients with the use of radioimmunoassay and enzyme-linked immunosorbent assay. Vitreous proliferative potential was measured according to the growth of retinal endothelial cells in vitro and with soluble erythropoietin receptor. In addition, a murine model of ischemia-induced retinal neovascularization was used to evaluate erythropoietin expression and regulation in vivo. RESULTS: The median vitreous erythropoietin level in 73 patients with proliferative diabetic retinopathy was significantly higher than that in 71 patients without diabetes (464.0 vs. 36.5 mIU per milliliter, P<0.001). The median VEGF level in patients with retinopathy was also significantly higher than that in patients without diabetes (345.0 vs. 3.9 pg per milliliter, P<0.001). Multivariate logistic-regression analyses indicated that erythropoietin and VEGF were independently associated with proliferative diabetic retinopathy and that erythropoietin was more strongly associated with the presence of proliferative diabetic retinopathy than was VEGF. Erythropoietin and VEGF gene-expression levels are up-regulated in the murine ischemic retina, and the blockade of erythropoietin inhibits retinal neovascularization in vivo and endothelial-cell proliferation in the vitreous of patients with diabetic retinopathy in vitro. CONCLUSIONS: Our data suggest that erythropoietin is a potent ischemia-induced angiogenic factor that acts independently of VEGF during retinal angiogenesis in proliferative diabetic retinopathy.

Animals↗
PubMed2005

De novo formation of left-right asymmetry by posterior tilt of nodal cilia.

In the developing mouse embryo, leftward fluid flow on the ventral side of the node determines left-right (L-R) asymmetry. However, the mechanism by which the rotational movement of node cilia can generate a unidirectional flow remains hypothetical. Here we have addressed this question by motion and morphological analyses of the node cilia and by fluid dynamic model experiments. We found that the cilia stand, not perpendicular to the node surface, but tilted posteriorly. We further confirmed that such posterior tilt can produce leftward flow in model experiments. These results strongly suggest that L-R asymmetry is not the descendant of pre-existing L-R asymmetry within each cell but is generated de novo by combining three sources of spatial information: antero-posterior and dorso-ventral axes, and the chirality of ciliary movement.

Animals↗
PubMed2005

Ion association dynamics in aqueous solutions of sulfate salts as studied by Raman band shape analysis.

A new perspective is shown on the interaction between the sulfate ion and its counter cation in aqueous solutions. We propose the dynamic exchange model of ion association instead of the conventional static equilibrium model. The concentration dependence of the Raman band shape of the totally symmetric (a(1)) SO stretch mode of the sulfate ion is investigated systematically for four sulfate ions, MgSO(4), (NH(4))(2)SO(4), K(2)SO(4), and Li(2)SO(4). The concentration dependence of the a(1) Raman band shape in the MgSO(4) system is successfully reproduced by the analysis based on the dynamic exchange model. As a result, quantitative information about the extremely dynamic nature of the ion association has been obtained: the mean time between associations is a few picoseconds and the mean lifetime of association is several hundred femtoseconds.

Journal Article↗
PubMed2005

Angiopoietin-1 attenuates H2O2-induced SEK1/JNK phosphorylation through the phosphatidylinositol 3-kinase/Akt pathway in vascular endothelial cells.

Oxidative stress activates various signal transduction pathways, including Jun N-terminal kinase (JNK) and its substrates, that induce apoptosis. We reported here the role of angiopoietin-1 (Ang1), which is a prosurvival factor in endothelial cells, during endothelial cell damage induced by oxidative stress. Hydrogen peroxide (H2O2) increased apoptosis of endothelial cells through JNK activation, whereas Ang1 inhibited H2O2-induced apoptosis and concomitant JNK phosphorylation. The inhibition of H2O2-induced JNK phosphorylation was reversed by inhibitors of phosphatidylinositol (PI) 3-kinase and dominant-negative Akt, and constitutively active-Akt attenuated JNK phosphorylation without Ang1. These data suggested that Ang1-dependent Akt phosphorylation through PI 3-kinase leads to the inhibition of JNK phosphorylation. H2O2-induced phosphorylation of SAPK/Erk kinase (SEK1) at Thr261, which is an upstream regulator of JNK, was also attenuated by Ang1-dependent activation of the PI 3-kinase/Akt pathway. In addition, Ang1 induced SEK1 phosphorylation at Ser80, suggesting the existence of an additional signal transduction pathway through which Ang1 attenuates JNK phosphorylation. These results demonstrated that Ang1 attenuates H2O2-induced SEK1/JNK phosphorylation through the PI 3-kinase/Akt pathway and inhibits the apoptosis of endothelial cells to oxidative stress.

Angiopoietin-1↗
PubMed2005

Gabexate mesilate, a synthetic protease inhibitor, attenuates carbon tetrachloride-induced liver injury in rats.

BACKGROUND: Gabexate mesilate, a synthetic protease inhibitor, is used to treat acute pancreatitis and disseminated intravascular coagulation because it inhibits various serine proteases; however, whether gabexate mesilate prevents acute liver failure has not yet been studied. The aim of the present study was to investigate the effect of gabexate mesilate in carbon tetrachloride (CCl4)-induced liver injury in rats. METHODS: Acute hepatic failure was induced by administration of CCl4 intragastrically to male Sprague-Dawley rats. The effects of gabexate mesilate were examined in terms of serum transaminase levels, liver histology, and the prognosis of rats. RESULTS: Gabexate mesilate treatment significantly decreased the elevation of serum transaminase levels and improved liver histology 24 h after the administration of CCl4 (0.2 ml/100 g rat weight). Plasma tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) decreased significantly in the gabexate mesilate-treated rats compared with saline-treated rats. Gabexate mesilate treatment also significantly improved survival rate after a lethal dose of CCl4 (0.5 ml/100 g rat weight) from 0% to 20%. CONCLUSIONS: Gabexate mesilate treatment attenuated CCl4-induced liver injury via a suppression of proinflammatory cytokine production. In addition, these investigations suggest that gabexate mesilate treatment may provide therapeutic strategies for human acute liver failure.

Animals↗
PubMed2005

Vitreous levels of angiopoietin 2 and vascular endothelial growth factor in patients with proliferative diabetic retinopathy.

PURPOSE: To investigate the levels of angiopoietin-2 (Ang2) and vascular endothelial growth factor (VEGF) in the vitreous fluids of patients with proliferative diabetic retinopathy (PDR) and to ascertain their involvement, if any, in angiogenesis of PDR. DESIGN: Retrospective case-control study. METHODS: Forty-one eyes of 41 patients with proliferative diabetic retinopathy and 18 eyes of 18 patients with nondiabetic ocular diseases (control group). Nondiabetic control eyes included 11 with idiopathic macular hole and 7 with idiopathic epiretinal membrane. Vitreous fluid samples were obtained at vitrectomy, and the levels of Ang2 and VEGF were measured by enzyme-linked immunosorbent assay. RESULTS: Vitreous level (mean +/- SD) of Ang2 was significantly higher in patients with PDR (1,753 +/- 3,213 pg/ml) than in control patients (112 +/- 113 pg/ml) (P < .0001). The vitreous concentration of VEGF was also significantly higher in patients with PDR (812 +/- 1,108 pg/ml) than in control patients (1.7 +/- 4.4 pg/ml) (P < .0001). Both Ang2 and VEGF levels in eyes with active PDR were significantly higher than in those with inactive PDR. The vitreous concentration of Ang2 correlated significantly with that of VEGF in eyes with proliferative diabetic retinopathy ([correlation coefficient] rho = 0.497, P = .001). CONCLUSIONS: These data demonstrate an increase of Ang2 in the vitreous fluid of patients with PDR and suggest an association of Ang2 and VEGF with angiogenic activity in PDR.

Angiopoietin-2↗
PubMed2005

Efficacy of surgical removal of the internal limiting membrane in diabetic cystoid macular edema.

PURPOSE: To evaluate the efficacy of surgical removal of the internal limiting membrane (ILM) in diabetic cystoid macular edema (CME). METHODS: Prospective, noncomparative, interventional case series including 21 eyes of 18 consecutive patients with diabetic CME. Vitrectomy with separation of the posterior hyaloid and induction of posterior vitreous detachment had been performed previously on nine eyes. Pars plana vitrectomy for removal of the ILM was performed. RESULTS: CME resolved in eyes that underwent initial vitrectomy and in those with long-standing (>1 year) CME after previous vitrectomy. Postoperative best-corrected visual acuity improved by >/=2 lines of a Snellen equivalent in 14 eyes (67%) (P < 0.01). The mean foveal thickness (distance between the inner retinal surface and the retinal pigment epithelium) decreased from 553 microm to 221 microm at 4 weeks (P < 0.001). No recurrences or deterioration of CME was observed during the entire follow-up period (mean, 17.8 months; range, 8-34 months). CONCLUSION: Surgical removal of the ILM might be an effective procedure for reducing CME in patients with diabetes. A prospective, randomized, controlled study is necessary to further evaluate the efficacy of the procedure.

Adult↗
PubMed2005

5-Aminolevulinic acid-based photodynamic therapy for the treatment of two patients with extramammary Paget's disease.

Photodynamic therapy (PDT), which employs a combination of a tumor-localizing photosensitizer and visible light, has been used in the treatment of extramammary Paget's disease (EMPD). Two patients with EMPD were treated with PDT using 5-aminolevulinic acid (ALA). Histologically, in both cases, Paget's cells were present within the epidermis. Case 1 was a 92-year-old male who underwent total extirpation for treatment of EMPD. Two topical ALA-PDT treatments were applied to parts of the lesions at a total dose of 200J/cm2. Case 2 was a 73-year-old female, whose lesions in the right labia majora were treated with 3 topical ALA-PDT sessions at a total dose of 300 J/cm2. Clinical findings after the irradiation showed improvement in both patients, and elimination of tumor cells in the epidermis was confirmed histologically. Case 1 had no recurrence in the irradiation field at three months after PDT. Case 2 had a recurrence only in the periphery parts of the lesions at two months after PDT, but the periphery lesions remitted with two more PDT treatments. Topical ALA-PDT is an effective treatment for EMPD with tumor cells within the epidermis. It is noninvasive and achieves a cosmetically excellent outcome, especially in elderly patients and those in poor general condition.

Aged↗
PubMed2005

Lymphoepithelioma-like carcinoma of the skin with potential for sweat glandular differentiation.

Lymphoepithelioma-like carcinoma of the skin (LELCS) is a cutaneous malignancy with histopathological resemblance to lymphoepithelioma of the nasopharynx. Its histogenesis remains unknown, and few cases showing skin appendage differentiation have been reported to date. We present the case of a 77-year-old Japanese male with an asymptomatic red nodule on his left cheek. Because the histopathological study revealed focal growth of tumor cells lacking connections with the epidermis and marked lymphocytic infiltration surrounding the neoplastic cell nests, the case was diagnosed as LELCS. On immunohistological staining, the neoplastic cells were positive for carcinoembryonic antigen (CEA), epithelial membrane antigen (EMA), multi-cytokeratin (CK), CK6, CK18, and CK19. On the basis of these results, we suggested that skin appendage differentiation, particularly sweat glandular differentiation, was present in this case.

Aged↗
PubMed2005

Distribution and isoforms of epimorphin in carbon tetrachloride-induced acute liver injury in mice.

BACKGROUND AND AIM: Epimorphin, a morphoregulatory factor essential to organ development, is believed to direct normal morphogenesis in tissue repair. We examined the dynamics and the roles of epimorphin, a cell surface-associated molecule detected on mesenchymal cells, in hepatic tissue repair from acute liver injury. METHODS: After acute liver injury was induced by carbon tetrachloride in Balb/c mice, the distribution of epimorphin-expressing cells was studied immunohistochemically. To clarify interactions between epimorphin expression and hepatocyte behavior, epimorphin-expressing cells and proliferating hepatocytes were counted. Then, epimorphin quantity and isoforms were assessed by western blotting. To better understand effects of epimorphin, we cultured rat hepatocytes in its presence. RESULTS: Epimorphin was distributed in relation to sinusoids, portal veins, central veins and granulomas, expressed in stellate cells and myofibroblasts. In the periportal zone, the expression in sinusoids was decreased at 24 h but increased on day 7 after carbon tetrachloride administration. Numbers of epimorphin-expressing cells and proliferating hepatocytes changed in an inverse manner as time progressed. In the pericentral zone, reactivity for epimorphin was markedly enhanced concurrently with appearance of granulomas. Quantities of 34-kDa isoform paralleled epimorphin-staining intensity. In vitro, epimorphin induced spherical hepatocyte aggregates and maintained differentiated hepatocyte function. CONCLUSIONS: Epimorphin is involved in tissue repair following a single injection of carbon tetrachloride, in which distribution and the quantity of epimorphin expression are important, particularly in maintaining hepatocyte function.

Acute Disease↗
PubMed2005

Evaluation of pretreatment with Pleurotus ostreatus for enzymatic hydrolysis of rice straw.

The effects of biological pretreatment of rice straw using four white-rot fungi (Phanerochaete chrysosporium, Trametes versicolor, Ceriporiopsis subvermispora, and Pleurotus ostreatus) were evaluated on the basis of quantitative and structural changes in the components of the pretreated rice straw as well as susceptibility to enzymatic hydrolysis. Of these white-rot fungi, P. ostreatus selectively degraded the lignin fraction of rice straw rather than the holocellulose component. When rice straw (water content of 60%) was pretreated with P. ostreatus for 60 d, the total weight loss and the degree of Klason lignin degraded were 25% and 41%, respectively. After the pretreatment, the residual amounts of cellulose and hemicellulose were 83% and 52% of those in untreated rice straw, respectively. By enzymatic hydrolysis with a commercial cellulase preparation for 48 h, 52% holocellulose and 44% cellulose in the pretreated rice straw were solubilized. The net sugar yields based on the amounts of holocellulose and cellulose of untreated rice straw were 33% for total soluble sugar from holocellulose and 32% for glucose from cellulose. The SEM observations showed that the increase in susceptibility of rice straw to enzymatic hydrolysis by pretreatment with P. ostreatus is caused by partial degradation of the lignin seal. When the content of Klason lignin was less than 15% of the total weight of the pretreated straw, enhanced degrees of enzymatic solubilization of holocellulose and cellulose fractions were observed as the content of Klason lignin decreased.

Biodegradation, Environmental↗
PubMed2005

Autoimmune hemolytic anemia in an elderly patient with primary Sjögren's syndrome.

Primary Sjögren's syndrome is an autoimmune disease characterized by lymphocytic infiltration of the salivary glands and lacrimal glands. The histological features of chronic inflammation in primary Sjögren's syndrome may be associated with B cell hyper-reactivity. This syndrome also has various manifestations associated with other exocrine glands and nonglandular tissues. The hematological abnormalities usually seen in Sjögren's syndrome are lymphopenia, leucopenia, and thrombocytopenia. Although the direct Coomb's test is often positive, the occurrence of autoimmune hemolytic anemia (AIHA) is rare. Here, we report an elderly patient with primary Sjögren's syndrome who developed AIHA during the clinical course.

Aged↗
PubMed2004

A novel GTPase activated by the small subunit of ribosome.

The GTPase activity of Escherichia coli YjeQ, here named RsgA (ribosome small subunit-dependent GTPase A), has been shown to be significantly enhanced by ribosome or its small subunit. The enhancement of GTPase activity was inhibited by several aminoglycosides bound at the A site of the small subunit, but not by a P site-specific antibiotic. RsgA stably bound the small subunit in the presence of GDPNP, but not in the presence of GTP or GDP, to dissociate ribosome into subunits. Disruption of the gene for RsgA from the genome affected the growth of the cells, which predominantly contained the dissociated subunits having only a weak activation activity of RsgA. We also found that 17S RNA, a putative precursor of 16S rRNA, was contained in the small subunit of the ribosome from the RsgA-deletion strain. RsgA is a novel GTPase that might provide a new insight into the function of ribosome.

Anti-Bacterial Agents↗
PubMed2004

Alterations in expression of angiopoietins and the Tie-2 receptor in the retina of streptozotocin induced diabetic rats.

PURPOSE: The angiopoietin (Ang)/Tie-2 system may play a role in vascular integrity and angiogenesis. In this study, we investigated alterations of the gene expression of Ang-1 and Ang-2 in the retinas of streptozotocin (STZ) induced diabetic rats. METHODS: In situ hybridization, reverse transcriptase polymerase chain reaction (RT-PCR) and western blot analyses were performed to determine the mRNA and protein content for Ang-1 and Ang-2 and the Tie2 receptor in the retinas of STZ diabetic and age matched control rats. RESULTS: Using in situ hybridization analysis, Ang-1, Ang-2, and Tie2 mRNA expression was observed in the ganglion cell layer (GCL) and the inner nuclear layer (INL). While Ang-2 mRNA expression did not changed after 2 weeks, 1 month, or 3 months of STZ induced diabetes, it was increased in the GCL and slightly elevated in the INL after 6 months of diabetes. In contrast, Ang-1 and Tie2 mRNA expression was stable at every timepoint during 6 months of STZ induced diabetes. RT-PCR and western blot analyses confirmed the increase of Ang-2 expression after 6 months of diabetes. Furthermore, double staining of alpha-smooth muscle actin (alphaSMA) and Ang-2 mRNA demonstrated that the SMA positive cells surrounding Ang-2-expressing cells were decreased in the GCL. CONCLUSIONS: Diabetes increases Ang-2 expression in the GCL accompanied by a reduction of alphaSMA positive perivascular cells. These changes may suggest a role for Ang-2 in the mechanism of pericyte loss in diabetic retinopathy.

Angiopoietin-1↗
PubMed2004

Phosphatidylinositol 3-kinase/Akt regulates angiotensin II-induced inhibition of apoptosis in microvascular endothelial cells by governing survivin expression and suppression of caspase-3 activity.

Angiotensin II (Ang II) plays essential roles in vascular homeostasis, neointimal formation, and postinfarct remodeling. Although Ang II has been shown to regulate apoptosis in cardiomyocytes and vascular smooth muscle cells, its role in vascular endothelial cells (ECs) remains elusive. To address this issue, we first performed TUNEL and caspase-3 activity assays with porcine microvascular ECs challenged by serum deprivation. Ang II significantly reduced the ratio of apoptotic cells and caspase-3 activity. The Ang II type 1 receptor (AT1) was responsible for these effects. Among the signaling molecules downstream of AT1, we revealed that PI3-kinase/Akt pathway plays a predominant role in the antiapoptotic effect of Ang II. Interestingly, the expression of survivin, a central molecule of cell survival, increased after Ang II stimulation. Overexpression of a dominant-negative form of Akt abolished both Ang II-induced antiapoptosis and survivin protein expression. In a murine model of hyperoxygen-induced retinal vascular regression, AT1a knockout mice showed a significant increase in retinal avascular areas. Our data indicate that Ang II plays a critical antiapoptotic role in vascular ECs by a mechanism involving PI3-kinase/Akt activation, subsequent upregulation of survivin, and suppression of caspase-3 activity.

Angiotensin II↗
PubMed2004

SCMD: Saccharomyces cerevisiae Morphological Database.

To study the global regulation of cell morphology, a number of groups have recently reported genome-wide screening data for yeast mutants with abnormal morphology. Despite the relatively simple ellipsoidal shape of yeast cells, in the past, cell morphology researchers have processed information on cells manually. These time-consuming, entirely subjective tasks motivated us to develop image-processing software that automatically extracts yeast cells from micrographs and processes them to measure key morphological characteristics such as cell size, roundness, bud neck position angle, nuclear DNA localization and actin localization. To date, we have retrieved 960,609 cells from 52,988 micrographs of 2531 mutants using our software, and we have published the results in the Saccharomyces cerevisiae Morphological Database (SCMD), which facilitates the analysis of abnormal cells. Our system provides quantitative data for shapes of the daughter and mother cells, localization of the nuclear DNA and morphology of the actin patches. To search for mutants with similar morphological traits, the system outputs a list of mutants ranked by similarity of average morphological parameters. The SCMD is available at http://yeast. gi.k.u-tokyo.ac.jp/.

Cell Cycle↗