Large-scale flooding analysis in the suburbs of Tokyo Metropolis caused by levee breach of the Tone River using a 2D hydrodynamic model.

In order to assess the effects of climate change on flood disasters in urban areas, we applied a two dimensional finite element hydrodynamic model (2D-FEM) to simulate flood processes for the case analysis of levee breach caused by Kathleen Typhoon on 16 September 1947 in Kurihashi reach of Tone River, upstream of Tokyo area. The purpose is to use the model to simulate flood inundation processes under the present topography and land-use conditions with impending extreme flood scenarios due to climate change for mega-urban areas like Tokyo. Simulation used 100 m resolution topographic data (in PWRI), which was derived from original LiDAR (Light Detection and Ranging) data, and levee breach hydrographic data in 1947. In this paper, we will describe the application of the model with calibration approach and techniques when applying for such fine spatial resolution in urban environments. The fine unstructured triangular FEM mesh of the model appeared to be the most capable of introducing of constructions like roads/levees in simulations. Model results can be used to generate flood mapping, subsequently uploaded to Google Earth interface, making the modeling and presentation process much comprehensible to the general public.

Effect of liver transplantation on transthyretin Tyr114Cys-related cerebral amyloid angiopathy.

OBJECTIVE: Patients with amyloidogenic transthyretin (ATTR) Tyr114Cys develop amyloid deposits in cerebral blood vessels, cerebral hemorrhage, and rapidly progressive dementia that presents with hereditary cerebral amyloid angiopathy (CAA). However, no treatment has been identified for CAA. Although liver transplantation has become an acceptable treatment of TTR-related amyloidosis, liver transplantation may not successfully treat CNS manifestations of the disorder. In this study, we examined the effect of liver transplantation on these manifestations of TTR-related CAA. METHODS: We compared clinical courses of three patients with CAA associated with ATTR Tyr114Cys who underwent liver transplantation with those of five patients with the disorder who did not undergo liver transplantation. RESULTS: The mortality and occurrence of cerebral hemorrhage and dementia in patients having transplantations were reduced compared with those in patients not having transplantations. The two groups did not differ with regard to the frequency of episodes of fluctuating consciousness and TIAs. The group undergoing transplantations had significantly smaller volumes of intracranial hemorrhage than did the no-transplantation group. CONCLUSION: Liver transplantation was effective for CNS manifestations of cerebral amyloid angiopathy associated with amyloidogenic transthyretin Tyr114Cys.

Search of type 2 diabetes susceptibility gene on chromosome 20q.

Significant evidence of linkage to type 2 diabetes (T2D) has been shown in a relatively broad region on chromosome 20q, where the hepatocyte nuclear factor-4alpha (HNF4A) has been noted as a positional candidate. To systematically evaluate genetic susceptibility to T2D in the relevant region, we examined the disease association by using 1145 SNPs in two-step screening in the Japanese population. The marker screening enabled us to identify significant disease association in the lipopolysaccharide binding protein (LBP) but not in the HNF4A locus. In a 17.7-Mb interval screened, the strongest association was identified for a SNP, rs2232592, located in the intron of LBP, with an estimated odds ratio of 1.73 (95% CI 1.30-2.31) (P=0.0002) in the whole study panel involving 675 case and 474 control subjects. Our data suggest that the LBP gene may confer genetic susceptibility to T2D and this warrants further replication study.

Separation of cashew (Anacardium occidentale L.) nut shell liquid with supercritical carbon dioxide.

Cashew nut shell liquid (CNSL) represents the largest readily available bioresource of alkenyl phenolic compounds. In this work, separation of CNSL from the pericarp of the cashew nut with supercritical carbon dioxide was studied. In the initial extractions with CO(2) at 40-60 degrees C and at pressures from 14.7 to 29.4 MPa, low yields were obtained. However, when the extractions were performed with one or more intermediate depressurization steps, the yield of CNSL increased to as high as 94%. Most of the oil did not separate from the shell during the depressurization step, but was obtained during the subsequent repressurization. The CNSL extract had a clear light brownish pink color and exhibited no evidence of polymerization or degradation. The pressure profile extraction method proposed in this work increases the possible CNSL extraction yields and greatly reduces the amount of CO(2) required for CNSL separation.

Interferon beta affects retinal pigment epithelial cell proliferation via protein kinase C pathways.

BACKGROUND: The aim of this study is to see the effect of interferon beta (IFN-beta) on cell proliferation and the protein kinase C (PKC) signaling pathway. METHODS: Proliferation of cultured human retinal pigment epithelium (RPE) cells, with various concentrations of IFN-beta, and with or without 3% fetal calf serum (FCS), was assessed by cell counting. Effects of short (3 h) or prolonged (48 h) exposure of RPE cells to natural human IFN-beta were assessed by (3)H-thymidine uptake. Cytosolic and membranous PKC activity over time in cells treated with IFN-beta and calphostin C was also measured. RESULTS: IFN-beta inhibited the increased proliferation by FCS in the prolonged-exposure assay. The PKC inhibitor calphostin C also showed an inhibitory effect on RPE cell growth and (3)H-thymidine uptake in the chronic exposure with FCS. Short treatment with IFN-beta had no inhibitory or stimulatory effect on (3)H-thymidine uptake. Cytosolic and membranous PKC activity was strongly upregulated after short IFN-beta exposure but returned to original levels after 1 h. PKC activity was downregulated both in the cytosol and membrane after 24 or 48 h. CONCLUSION: IFN-beta inhibited RPE proliferation in vitro and the effect is mediated by upregulation of the PKC pathway.

Surgical outcomes of trabeculotomy combined with sinusotomy for juvenile glaucoma.

PURPOSE: To evaluate the outcome of trabeculotomy combined with sinusotomy for juvenile glaucoma. METHODS: We studied 16 patients (25 eyes) (age range, 11-50 years) with juvenile glaucoma for a minimum follow-up period of 1 year. We performed combined trabeculotomy and sinusotomy surgery in 13 juvenile glaucoma patients (18 eyes), and trabeculotomy alone in 6 patients (7 eyes). RESULTS: The intraocular pressure (IOP) of the combined surgery group was 29.8 +/- 7.8 mm Hg before surgery and 15.6 +/- 3.0 mm Hg 1 year after surgery. The IOP of the trabeculotomy-alone group was 29.1 +/- 6.4 mm Hg before surgery and 15.4 +/- 2.4 mm Hg 1 year after surgery. A postoperative IOP spike that was higher than the preoperative IOP was recorded in 2 eyes of the combined surgery group and in 2 eyes of the trabeculotomy group. The combined surgery group consisted of 7 eyes with a previously failed glaucoma surgery, and 11 eyes having a first glaucoma surgery. The postoperative IOP in these 11 eyes was 15.5 +/- 2.8 mm Hg. CONCLUSION: Trabeculotomy is very effective in lowering the IOP in patients with juvenile glaucoma. Sinusotomy does not play an important role in tension control.

Depigmented atrophic lesions in sunset glow fundi of Vogt-Koyanagi-Harada disease.

PURPOSE: Although the depigmented, small, round to oval lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are considered to represent Dalén-Fuchs nodules, there is no histopathologic evidence to support such a consideration. An attempt is made herein to clarify the nature of the atrophic lesions and distinguish them from Dalén-Fuchs nodules seen in eyes with Vogt-Koyanagi-Harada disease. METHODS: Eyes from five individuals with clinical diagnoses of Vogt-Koyanagi-Harada disease were subjected to histopathologic examination. The retinal pigment epithelial changes from early active to convalescent and late chronic recurrent stages were evaluated. Particular attention was paid to Dalén-Fuchs nodules, depigmented lesions in the sunset glow fundi, and hyperpigmentation of the chronic recurrent stage. RESULTS: Eyes of two individuals, one in the active stage of Vogt-Koyanagi-Harada disease and the other in the convalescent stage, showed the presence of Dalén-Fuchs nodules. The depigmented small retinal pigment epithelial lesions were seen in two individuals, both of whom exhibited the sunset glow fundus of the convalescent stage. The retinal pigment epithelial lesions represented damage or disappearance of retinal pigment epithelial cells, and the sunset glow fundus appearance was from the loss of choroidal melanocytes. The heavy pigmentation seen in fundi with the chronic recurrent stage was the result of the proliferation of retinal pigment epithelial cells. CONCLUSION: The Dalén-Fuchs nodule is a specific histologic change observed at the level of retinal pigment epithelium in patients with Vogt-Koyanagi-Harada disease. There is no histologic confirmation that the depigmented small atrophic lesions seen in the sunset glow fundi of Vogt-Koyanagi-Harada disease are Dalén-Fuchs nodules. The depigmented lesions represent localized damage or disappearance of retinal pigment epithelial cells.

Relocalization of apoptosis-inducing factor in photoreceptor apoptosis induced by retinal detachment in vivo.

Apoptosis-inducing factor (AIF) is a novel mediator in apoptosis. AIF is a flavoprotein that is normally confined to the mitochondrial intermembrane space, yet translocates to the nucleus in several in vitro models of apoptosis. To investigate the role of AIF in the apoptotic process in vivo, we induced retinal detachment (RD) by subretinal injection of sodium hyaluronate, either in Brown Norway rats or in C3H mice. Apoptotic DNA fragmentation, as determined by terminal nick-end labeling, was most prominent 3 days after RD. The subcellular localization of AIF was examined by immunohistochemistry and immunoelectron microscopy. In normal photoreceptor cells, AIF was present in the mitochondrion-rich inner segment. However, AIF was found in the nucleus after RD. Photoreceptor apoptosis developed similarly in C3H control mice, and in mice bearing the gld or lpr mutations, indicating that cell death occurs independently from the CD95/CD95 ligand system. Both the mitochondrio-nuclear transition of AIF localization and the nuclear DNA fragmentation were inhibited by subretinal application of brain-derived neurotrophic factor. To our knowledge, this is the first description of AIF relocalization occurring in a clinically relevant, in vivo model of apoptosis.

Tissue factor increases in the aqueous humor of proliferative diabetic retinopathy.

BACKGROUND: Tissue factor (TF) is a cellular initiator of the coagulation cascade and is upregulated by the major factors of diabetic angiopathy, TF might thus be one of the key molecules in diabetic retinopathy (DR). PURPOSE: To measure TF in diabetic eyes and evaluate its possible role in DR. METHODS: TF concentration in the aqueous humor of the eyes in 44 patients with diabetes and 35 age-matched control patients was evaluated by ELISA. The concentration of TF in aqueous humor (AH) was compared with the grade of DR. The concentration of TF in AH was also compared with duration of diabetes, renal function, and blood glucose control. The serum TF concentration in each group was also compared. The correlation between the serum TF and aqueous TF in each patient was analyzed. The effect of vascular endothelial growth factor (VEGF) on the TF activity of cultured bovine retinal endothelial cells was evaluated. RESULTS: The mean TF concentration in AH was higher in patients with active proliferative DR (244.5 pg/ml) than in either those with non-proliferative DR (132.4 pg/ml, P<0.05) or the control patients (114.9 pg/ml, P<0.01). The serum TF concentration in active proliferative DR patients (348.3 pg/ml) was significantly higher than in either non-proliferative DR patients, (235.9 pg/ml, P<0.01) or in the controls (223.5 pg/ml, P<0.01). However, the TF concentration of AH was not significantly correlated to that of the serum in each patient. The TF concentration in AH closely correlated with the grade of DR and protein concentration. VEGF increased the biological activity of TF in vitro. CONCLUSION: The origin of TF in AH, however, is still not clearly understood. Nonetheless, TF in AH directly reflects the severity of ocular diabetic change, and the present results indicate that TF indeed plays some role in the progression of DR.

Increased expression of angiotensin-converting enzyme in retinas of diabetic rats.

PURPOSE: The aim of this study was to examine the localization and the changes in the amount of angiotensin-converting enzyme (ACE) and the relationship between the renin-angiotensin (RA) system and vascular endothelial growth factor (VEGF)/VEGF-receptor system in the retinas of diabetic rats. METHODS: Immunohistochemical localization of ACE, VEGF, and VEGF-receptor fetal liver kinase-1 (Flk-1) was examined in cryosections of the retinas of streptozotocin-injected diabetic rats. A semi-quantitative comparison of diabetic rats with age-matched controls was also performed by counting the ACE- or Flk-1-positive vessels per microscopic field. RESULTS: ACE immunoreactivity was localized in the retinal vessel walls, and the percentages of ACE-positive vessels were significantly increased in the retinas of diabetic rats maintained 3 to 5 months. Both VEGF and Flk-1 signals increased simultaneously with the increment of ACE immunoreactivity. CONCLUSIONS: ACE, expressed in the retinal vessel walls, increases simultaneously with the increment of both VEGF and Flk-1 in the retinas of diabetic rats, suggesting that upregulation of ACE might play some role in the progression of diabetic retinopathy through the VEGF/VEGF receptor system.

Control of methanol oxidation by ionic behavior in supercritical water.

In supercritical water the rate of methanol oxidation was controlled by ionic behavior as follows: the oxidation rate of methanol decreased with increasing proton and hydroxide ion concentration, possibly due to stabilization of the reactant, while that of CO was suppressed by added protons and enhanced by added hydroxide ions.

High prevalence of antineutrophil cytoplasmic antibody positivity in childhood onset Graves' disease treated with propylthiouracil.

Propylthiouracil (PTU)-induced antineutrophil cytoplasmic antibody (ANCA)-related vasculitis and nephritis were recently reported in about 30 patients with hyperthyroidism. The objective of this study was to clarify the prevalence of ANCA and the relationship between ANCA and thyroid antibodies in children with Graves' disease. Titers of myeloperoxidase (MPO)-ANCA in sera of 51 patients with childhood onset Graves' disease (16 before treatment, 25 and 10 treated with PTU and methimazole, respectively) were measured by enzyme-linked immunosolvent assay. Antithyroglobulin antibodies (TGAbs) and antithyroperoxidase antibodies (TPOAbs) were also measured by RIA in 25 PTU-treated patients. No patients had clinical manifestations of vasculitis and nephritis. MPO-ANCA was positive in 6.7% of patients before treatment and in 64.0% of those treated with PTU and in none of those treated with methimazole. MPO-ANCA had a significantly positive correlation with TGAbs (P < 0.05) and no significant correlation with TPOAbs. These findings show the high prevalence of the MPO-ANCA positivity in PTU-treated childhood onset Graves' disease, suggesting that PTU may not be preferred as the first line for the treatment of children with Graves' disease. The significant correlation between MPO-ANCA and TGAbs indicates that the severity of Graves' disease may be a factor responsible for the MPO-ANCA positivity. The cross-reactivity between MPO-ANCA and TPOAbs may not play a role in the high prevalence of MPO-ANCA in the patients exposed to PTU.

The suppressive effect of tecogalan sodium on in vitro angiogenesis via the periendothelial proteolytic activities.

The exact mechanisms of the angiostatic effect by tecogalan sodium (TS) remain unclear. We examined the effects of TS on in vitro angiogenic activity, proteolytic activity and proliferation of retinal vascular endothelial cells (RECs). TS markedly inhibited the in vitro angiogenic activity of RECs although the growth inhibition of RECs was small. TS apparently decreased the cell-associated urokinase-type plasminogen activator (uPA) activity and matrix metalloprotease 1 (MMP-1) activity even in the presence of anti-bFGF IgG. Thus, the suppression of the periendothelial matrix-degrading activities related to uPA and MMP-1 is suggested to be another possible mechanism of the antiangiogenic effect of TS, besides its prevention of bFGF REC binding which has previously been reported.

Gene transfer of a soluble receptor of VEGF inhibits the growth of experimental eyelid malignant melanoma.

PURPOSE: To determine the effect of adenovirus-mediated gene transfer of a soluble receptor of vascular endothelial growth factor (VEGF) on the growth of experimental eyelid malignant melanoma. METHODS: An adenovirus vector encoding a soluble VEGF receptor/flt-1 (Adflt-ExR) was constructed. The bovine retinal endothelial cells (ECs) were incubated in a culture medium of 293E1 cells infected by means of an adenovirus vector or uninfected (control), which contained human recombinant VEGF, and the [3H]thymidine uptake was tested. The experimental eyelid malignant melanoma was induced by the injection of B16 melanoma cells (4 x 10(6) cells) into the right upper eyelid of BALB/c nu/nu mice, and the size of the tumor was recorded for 3 weeks after tumor cell injection. The effect of Adflt-ExR was examined in three ways. Model 1: B16 cells were infected by Adflt-ExR beforehand (at a multiplicity of infection [MOI] of 10) and injected into the eyelid. Model 2: Adflt-ExR was injected into pre-established B16 cell-induced eyelid malignant melanoma. Model 3: Adflt-ExR was injected into the femoral muscle of mice before B16 cell injection into the eyelid, and the remote effect was evaluated. An adenovirus vector bearing the LacZ gene (AdLacZ) or phosphate-buffered saline was used as a control. The amount of VEGF and the flt-ExR protein was measured by sandwich enzyme-linked immunosorbent assay (ELISA). Vascularization was evaluated by counting the number and the size of the vessels. RESULTS: The supernatant of Adflt-ExR-transfected cells clearly inhibited VEGF-induced bovine retinal EC proliferation in vitro. In models 1 and 2, the tumor growth in Adflt-ExR-treated mice was significantly lower than that of controls (P < 0.05). In model 3, no significant difference was found (P = 0.14). The molar ratio of VEGF/flt-ExR protein was clearly low in the tumors of Adflt-ExR-treated mice in models 1 and 2 (P < 0.01) but not in model 3 (P > 0.05). In vessel density, the tumors in Adflt-ExR-treated mice had fewer vessels than tumors in control animals in models 1 and 2 (P < 0.05). CONCLUSIONS: Adenovirus-mediated gene transfer of a soluble form of VEGF receptor (flt-1) gene inhibited the growth of the experimental eyelid malignant melanoma. This method may be useful as an antiangiogenic therapy for eyelid malignant melanoma.

Experimental subretinal neovascularization is inhibited by adenovirus-mediated soluble VEGF/flt-1 receptor gene transfection: a role of VEGF and possible treatment for SRN in age-related macular degeneration.

Accumulating evidence has shown the importance of vascular endothelial growth factor (VEGF) in chorioretinal angiogenesis. However, whether or not VEGF is indeed critical for the pathogenesis of subretinal neovascularization (SRN) in adulthood, which is a serious complication of age-related macular degeneration, has to be further investigated. We constructed an adenovirus expressing an entire ectodomain of the human VEGF receptor/flt-1 fused to Fc portion of human IgG (Adflt-ExR): this soluble receptor is secreted from Adflt-ExR-transfected cells. We studied the effect of Adflt-ExR on the formation of experimental SRN. Experimental SRN was induced by intense photocoagulation on the retina in pigmented rats and Adflt-ExR was injected into the femoral muscle. The formation of SRN assessed by fluorescein angiography was more significantly inhibited for 7 days in the Adflt-ExR-treated rats than in the control rats who received either an adenovirus vector encoding LacZ gene or balanced salt solution (BSS). The serum concentration of this soluble receptor increased for 7 days and thereafter gradually decreased. An immunohistochemical study disclosed the fibroblast cell proliferation and inflammatory cell infiltration to be reduced in the photocoagulation spot of Adflt-ExR-treated rats. VEGF plays a crucial role in the formation of SRN and VEGF soluble receptor gene transfection can inhibit SRN. This method will contribute to future gene therapy for age-related macular degeneration.

[A case of ring 14 chromosome with ocular manifestations].

BACKGROUND: Ring 14 chromosome has been reported to be associated with mental retardation, craniofacial dysmorphology, and epilepsy. Flecked and/or pigmented retina are also ocular manifestations of this disease. CASE: A 29-year-old female suffered from seizures and developmental and growth delay. Narrow palpebral fissura, broad flat nose, large auricula, high arched palate, and short neck were present. Chromosomal analysis disclosed her ring 14 chromosome (p 11.2 q 32.3). Ophthalmologically, cortical cataract, refractive error (right--3.00 D, left--1.50 D), and yellow-white flecks in the macula and yellow-white spots in the mid-peripheral retina in both eyes were present. CONCLUSIONS: To date, ophthalmic changes concomitant to a breakpoint at 14 q 32.2 have been reported. We report a case of ring 14 chromosome with breakpoint at 14 q 32.3 which showed yellow flecks in the macula and mid-peripheral retina.