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Hirokazu Ohashi

Publications and source records attributed to Hirokazu Ohashi.

At least 19 recordsLinked to original sources
PubMed2006

Intravitreal tissue plasminogen activator to treat macular edema associated with branch retinal vein occlusion.

PURPOSE: To evaluate the efficacy of intravitreal tissue plasminogen activator (tPA) injection for branch retinal vein occlusion (BRVO). DESIGN: Retrospective, interventional case series. METHODS: Seventeen eyes presenting with macular edema caused by BRVO were treated with an intravitreal tPA (Monteplase, 40 k IU) injection. We assessed the visual acuity (VA) and foveal thickness measured with optical coherence tomography. RESULTS: The mean duration of symptoms before surgery was 3.6 +/- 3.8 weeks. The mean logMAR VA significantly improved from 0.603 +/- 0.327 at baseline to 0.388 +/- 0.248 (P < .01) at one month and 0.359 +/- 0.319 (P < .05) at six months. The mean foveal thickness significantly decreased from 738 +/- 156 microm at baseline to 454 +/- 213 microm (P < .001) at one month and 253 +/- 164 microm (P < .001) six months. CONCLUSION: Intravitreal tPA injection may be an effective treatment for resolving macular edema and improving the VA in BRVO.

Aged↗
PubMed2006

Biventricular pacing 18 months after Batista operation.

We conducted biventricular pacing in a patient with dilated cardiomyopathy and complete left bundle branch block who had recurrent heart failure and mitral valve regurgitation 18 months after partial left ventriculectomy and mitral valve repair. An epicardial lead was fixed on the left ventricular free wall surgically through a thoracotomy, and the other two leads were implanted transvenously. Biventricular pacing restored contractile synchrony and led to more efficient left ventricular contraction and reductions in mitral regurgitation. Biventricular pacing may produce beneficial effects for patients with the recurrent intractable heart failure associated with cardiomyopathy and complete left bundle branch block after partial left ventriculectomy.

Bundle-Branch Block↗
PubMed2006

Time-lapse imaging of vitreoretinal angiogenesis originating from both quiescent and mature vessels in a novel ex vivo system.

PURPOSE: Diabetic retinopathy (DR) is an angiogenic disease that leads to severe visual loss. However, adequate animal models of vitreoretinal neovascularization in proliferative diabetic retinopathy (PDR) have not yet been described. The purpose of this study was to develop a novel ex vivo system for assessing vitreoretinal angiogenic processes that originate from both quiescent and mature vessels that could be observed with time-sequential imaging. METHODS: The retinas of 7- to 8-week-old mice were cultured for 4 days, with or without several growth factors with novel procedures, and immunohistochemistry was performed. The retinas from Tie2-GFP mice were cultured with vascular endothelial growth factor (VEGF), and time-sequential imaging of vitreoretinal angiogenesis was acquired. RESULTS: Vascular sprouts were induced by both VEGF and placenta growth factor, but not by insulin-like growth factor-1, basic fibroblast growth factor or angiopoietin-2. In explants with or without VEGF, perivascular mural cells were dissociated from endothelial cells, which is an important step during angiogenesis and in the progression of DR. Furthermore, use of time-lapse observations of retinal neovascularization events visualized that the first step in vascular sprout emergence from quiescent vessels was a single cell extension. The leading edges of a sprouting endothelial cell extended and retracted in a sequential manner. From newly formed vessels, additional vascular sprouts then emerged and new vessels fused to each other, resulting in vascular branching. CONCLUSIONS: Time-lapse imaging of this system visualized the dynamic process in vitreoretinal neovascularization from quiescent and mature vessels.

Animals↗
PubMed2006

Three cases of iatrogenic coronary ostial stenosis after aortic valve replacement.

BACKGROUND: Iatrogenic coronary ostial stenosis (ICOS) is a rare but potentially life-threatening complication of aortic valve replacement (AVR). This complication is usually diagnosed by angiography and treated with aortocoronary bypass surgery. CASE REPORTS: In the present 3 cases pre-operative coronary angiography confirmed normal coronary arteries and they underwent uncomplicated AVR. Coronary lesions were clinically manifest within 4 months after surgery, and repeat coronary angiography demonstrated bilateral ostial stenosis in 1 patient and left main trunk stenosis in the other 2. Two cases were detected by multidetector computed tomography (MDCT) before angiography. MDCT and Virtual Histology suggested fibrous tissue formation in the lesions. All 3 patients were successfully underwent percutaneous coronary intervention (PCI) and stenting. The post-procedure clinical course has been uneventful, except for elective stenting of a recurrent lesion in 1 asymptomatic patient. CONCLUSIONS: The incidence of ICOS after AVR is low. Noninvasive MDCT is useful for early diagnosis and PCI is a possible alternative treatment. ICOS may be caused by fibrous tissue formation, and therefore be distinct from conventional atherosclerosis.

Aged↗
PubMed2006

EphrinA1 inhibits vascular endothelial growth factor-induced intracellular signaling and suppresses retinal neovascularization and blood-retinal barrier breakdown.

The Eph receptor/ephrin system is a recently discovered regulator of vascular development during embryogenesis. Activation of EphA2, one of the Eph receptors, reportedly suppresses cell proliferation and adhesion in a wide range of cell types, including vascular endothelial cells. Vascular endothelial growth factor (VEGF) plays a primary role in both pathological angiogenesis and abnormal vascular leakage in diabetic retinopathy. In the study described herein, we demonstrated that EphA2 stimulation by ephrinA1 in cultured bovine retinal endothelial cells inhibits VEGF-induced VEGFR2 receptor phosphorylation and its downstream signaling cascades, including PKC (protein kinase C)-ERK (extracellular signal-regulated kinase) 1/2 and Akt. This inhibition resulted in the reduction of VEGF-induced angiogenic cell activity, including migration, tube formation, and cellular proliferation. These inhibitory effects were further confirmed in animal models. Intraocular injection of ephrinA1 suppressed ischemic retinal neovascularization in a dose-dependent manner in a mouse model. At a dose of 125 ng/eye, the inhibition was 36.0 +/- 14.9% (P < 0.001). EphrinA1 also inhibited VEGF-induced retinal vascular permeability in a rat model by 46.0 +/- 10.0% (P < 0.05). These findings suggest a novel therapeutic potential for EphA2/ephrinA1 in the treatment of neovascularization and vasopermeability abnormalities in diabetic retinopathy.

Animals↗
PubMed2006

[A case of AFP and PIVKA-II producing gastric carcinoma].

A 71-year-old man was admitted to our hospital with edema of the ambilateral crura and liver dysfunction. Serum levels of AFP and PIVKA-II were both abnormally high. An abdominal CT revealed many low density masses in both lobes of the liver. Endoscopic examination and gastric radiography showed a Type 1 tumor in the fornix of the stomach. Biopsy specimen showed poorly differentiated adenocarcinoma. Immunohistochemical stains demonstrated the presence of AFP and PIVKA-II in tumor cells. A diagnosis of AFP and PIVKA-II producing gastric carcinoma with liver metastasis was made and the internal use of S-1 was started. The result of treatment was determined to be partial response. However, the condition of his entire body gradually worsened and he died of hepatic insufficiency.

Adenocarcinoma↗
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

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

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↗
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

Morphological changes in the optic disc after vitrectomy and fluid-air exchange.

BACKGROUND: Although many investigators have previously reported various ocular complications induced by vitrectomy, little is known about post-operative morphological changes in the optic disc. The purpose of this study is to evaluate the effect of vitrectomy and fluid-air (F-A) exchange on the post-operative morphology of the optic disc. METHODS: We examined 31 eyes that had undergone vitrectomy for macular holes (22 eyes) or epiretinal membranes (9 eyes). Only the patients with macular holes were treated by fluid-air exchange. Morphological changes in the optic disc were evaluated using the Heidelberg Retina Tomograph. RESULTS: C/D area ratios significantly decreased for 6 months post-operatively. The rim volumes significantly increased for 1 month following surgery. Cup volumes significantly decreased at 3 months after surgery. No significant change of mean cup depth was observed post-operatively. The eyes that had not been subjected to F-A exchange showed no significant morphological change following surgery. In contrast, the eyes that had undergone F-A exchange showed significant decrease in C/D area ratio and cup volume and an increase in rim volume and mean cup depth for considerable periods following surgery. Any of the patients showed no post-operative visual field loss. CONCLUSION: Whereas no visual field loss is observed, vitrectomy with F-A exchange induces morphological changes in the optic disc for significant periods following surgery.

Adult↗
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

Radionuclide study of mid-term left ventricular function after endoventricular circular patch plasty.

OBJECTIVE: Although the early result of endoventricular circular patch plasty (EVCPP) has been reported, few are seen about the long-term results. We studied left ventricular (LV) function in the early and mid-term periods after EVCPP with electrocardiographic-gated single photon emission computed tomography (Gated SPECT). METHODS: Consecutive 14 patients with LV asynergy after myocardial infarction, who had the EVCPP procedure, were studied by Gated SPECT. Mean age of patients was 67+/-10 years. Gated SPECT images were obtained and LV end-diastolic volume index (EDVI), LV end-systolic volume index (ESVI) and ejection fraction (EF) were studied with QGS(+) program. Gated SPECT study was performed before surgery, early (23 days) and mid-term periods (32 months) after surgery. RESULTS: EDVI changed significantly from preoperative value to early postoperative value (107+/-39 to 72+/-37 ml/m(2), P < 0.01). There was no significant difference between early and mid-term postoperative values. ESVI also changed significantly from preoperative value to early postoperative value, and from early value to mid-term postoperative value (78+/-37 to 51+/-34 to 47+/-35 ml/m(2), P < 0.05, respectively). EF increased significantly from preoperative value to early postoperative value, and from early value to mid-term postoperative value (30+/-10 to 35+/-13 to 45+/-18%, P < 0.05, respectively). CONCLUSIONS: Direct influence of EVCPP brought significant improvement of LV function in early period. Further decrease of ESVI and increase of EF were noticed from early period to mid-term period. This result suggest that the effect of EVCPP sustains long and yields reverse LV remodeling.

Aged↗
PubMed2004

Delayed absorption of macular edema accompanying serous retinal detachment after grid laser treatment in patients with branch retinal vein occlusion.

PURPOSE: To study the detailed process of macular edema (ME) absorption after grid laser photocoagulation in patients with branch retinal vein occlusion (BRVO). The influence of pretreatment serous retinal detachment (SRD) at the fovea on patient outcome was also evaluated. DESIGN: Retrospective, interventional, comparative case series. PARTICIPANTS: Thirty-seven BRVO patients presenting with severe ME. METHODS: Patients were treated with grid laser photocoagulation with 6 months of follow-up examinations. Baseline and post-treatment examinations included measurements of visual acuity (VA), fluorescein angiography, and detailed imaging of ME by optical coherence tomography (OCT). Macular thickness was defined as the distance from the inner retinal surface to the outer border of the sensory retina (foveal retinal thickness) and also to the inner border of the retinal pigment epithelium including the SRD (total foveal elevation). MAIN OUTCOME MEASURES: Post-treatment macular thickness with OCT, VA converted to the logarithm of the minimum angle of resolution, and absorption of SRD, and correlations of macular thickness and VA both before and after treatment. RESULTS: Total foveal elevation and VA were significantly improved at 1, 3, and 6 months after treatment. There was also a significant correlation between reduction of total foveal elevation and increase in VA. Fourteen eyes (37.8%) displayed SRD, as evidenced by OCT at the baseline. In eyes without SRD, foveal retinal thickness and VA had significantly improved in a time-dependent manner. However, although SRD itself was almost absorbed 6 months after treatment, the improvement of both VA and total foveal elevation in eyes with pretreatment SRD was not significant compared with baseline conditions. Both post-treatment total foveal elevation and VA of eyes with SRD tended to be worse than eyes without SRD. CONCLUSION: The presence of subfoveal SRD retards the absorption of ME and recovery of VA after grid laser photocoagulation in patients with BRVO.

Absorption↗
PubMed2004

Transcription factor Ets-1 mediates ischemia- and vascular endothelial growth factor-dependent retinal neovascularization.

Transcription factor Ets-1 has been reported to regulate angiogenesis in vascular endothelial cells. Here, we investigated a mechanism that may regulate the expression of Ets-1 in vascular endothelial growth factor (VEGF)- and hypoxia-induced retinal neovascularization and that may have potential to inhibit ocular neovascular diseases. VEGF and hypoxia increased Ets-1 expression in cultured bovine retinal endothelial cells. The VEGF-induced mRNA increase of Ets-1 was suppressed by a tyrosine kinase inhibitor (genistein), by inhibitors of MEK (mitogen-activated protein and extracellular signal-regulated kinase kinase) (PD98059 and UO126), and by inhibitors of protein kinase C (GF109203X, staurosporine, and Gö6976). Dominant-negative Ets-1 inhibited VEGF-induced cell proliferation, tube formation, and the expression of neuropilin-1 and angiopoietin-2. In a mouse model of proliferative retinopathy, Ets-1 mRNA was up-regulated. Intravitreal injection of dominant-negative Ets-1 suppressed retinal angiogenesis in a mouse model of proliferative retinopathy. In conclusion, VEGF induces Ets-1 expression in bovine retinal endothelial cells and its expression is protein kinase C/ERK pathway-dependent. Ets-1 up-regulation is involved in the development of retinal neovascularization, and inhibition of Ets-1 may be beneficial in the treatment of ischemic ocular diseases.

Adenoviridae↗
PubMed2004

[A case of pityriasis rubra pilaris associated with rapidly progressive finger joint destruction].

A 40-year-old female noticed edema of the lower limbs in March 1995. Nephrotic syndrome due to membranous nephropathy was diagnosed and administration of high-dose corticosteroids resulted in incomplete remission. Progressively enlarging, red scaling skin lesions developed concomitantly from the scalp to the extremities. Pityriasis rubra pilaris (PRP) was diagnosed in 1996 in the Department of Dermatology at Sapporo Medical University hospital. Various treatments proved ineffective. Arthritis of the finger joints developed in July 1999, and proteinuria recurred in April 2000. She was admitted to our department in August 2000. Physical examination on admission revealed marked swelling of both distal interphalangeal (DIP) joints and the right fourth proximal interphalangeal (PIP) joint. Results of testing for antinuclear antibody, rheumatoid factor, and HLA-B27 were all negative. Radiography of the hands revealed destruction of the DIP and PIP joints where MRI indicated the presence of synovitis. Bone scintigraphy demonstrated accumulation in bilateral metatarso-phalangeal joints and the left sacroiliac joint. Arthritis associated with PRP was diagnosed, as both PRP and psoriasis represent keratinizing disorders of the skin and clinical features in the present case resembled those of psoriatic arthritis. Despite administration of high-dose corticosteroids, destruction of finger joints progressed rapidly. Administration of cyclosporine in April 2002 improved arthritic symptoms. Cases of PRP accompanied by arthritis need to be accumulated to allow analysis of the pathogenesis and clinical picture of this association.

Adult↗
PubMed2004

Leptin stimulates ischemia-induced retinal neovascularization: possible role of vascular endothelial growth factor expressed in retinal endothelial cells.

Diabetic retinopathy is the leading cause of new blindness in adults in developed countries. Leptin, an adipocyte-derived hormone, stimulates endothelial proliferation and angiogenesis. This study was designed to elucidate the pathophysiologic role of leptin in the progression of retinal neovascularization. Using the retinopathy of prematurity model, a mouse model of ischemia-induced retinal neovascularization, we have demonstrated more pronounced retinal neovascularization in 17-day-old transgenic mice overexpressing leptin than in age-matched wild-type littermates. Ischemia-induced retinal neovascularization was markedly suppressed in 17-day-old leptin-deficient ob/ob mice. Western blot analysis revealed that a biologically active leptin receptor isoform is expressed in mouse retinal endothelial cells. Leptin receptor expression was also detected in primary cultures of porcine retinal endothelial cells, where it upregulated vascular endothelial growth factor (VEGF) mRNA expression. This effect was thought to be mediated at least partly through the activation of signal transducers and activators of transcription (STAT)3, because adenoviral transfection of the dominant-negative form of STAT3 abolished the leptin-induced upregulation of VEGF mRNA expression in retinal endothelial cells. This study provides evidence that leptin stimulates the ischemia-induced retinal neovasucularization possibly through the upregulation of endothelial VEGF, thereby suggesting that leptin antagonism may offer a novel therapeutic strategy to prevent or treat diabetic retinopathy.

Animals↗