Clinical features of anterior uveitis caused by three different herpes viruses.

PURPOSE: To compare the clinical findings in patients with anterior uveitis (AU) caused by herpes simplex virus (HSV), varicella zoster virus (VZV), and cytomegalovirus (CMV). METHODS: We retrospectively analyzed the clinical profiles of HSV-AU (14 patients), VZV sine herpete (ZSH-AU: 21 patients), and CMV-AU (17 patients) diagnosed by the detection of corresponding viral DNA in aqueous humor samples by polymerase chain reaction. Further, five patients with Posner-Schlossman (P-S) syndrome were selected as controls for CMV-AU. RESULTS: Patients with CMV-AU were predominately male or older in age, and all cases were unilateral except for three patients with CMV-AU. Mutton-fat keratic precipitates (KPs) were found mostly in patients with HSV-AU and ZSH-AU. Severities of AU and viral load were the highest in ZSH-AU, followed by HSV-AU and CMV-AU. Iris atrophy was observed in HSV-AU (50%) and ZSH-AU (76%), with typical morphology of round type and sector type, respectively. In patients with CMV-AU, a ring-shaped KP was found in 53% patients, 76% of whom showed a decreased number of corneal endothelial cells. CMV was not detected in the aqueous humor of patients with typical P-S syndrome. CONCLUSION: Clinical findings of HSV-AU and VZV-AU were similar; however, more inflammatory findings were observed in VZV-AU. Iris atrophy morphologically differed in HSV-AU and VZV-AU. Inflammatory findings in CMV-AU were mild, and clinical features of iritis differed from those of the two former groups. A difference in the etiology between CMV-AU and P-S syndrome was observed.

Anti-TNF-α Therapy for Refractory Uveitis Associated with Behçet's Syndrome and Sarcoidosis: A Single Center Study of 131 Patients.

PURPOSE: The efficacy of infliximab (IFX) and adalimumab (ADA) for treating Behçet's syndrome (BS) and sarcoidosis has not been compared adequately. METHODS: We reviewed the medical records of patients with uveitis diagnosed at Tokyo Medical University Hospital and compared the efficacy of IFX and ADA for BS and the efficacy of ADA for sarcoidosis and BS. RESULTS: 68 patients in IFX group and 63 patients in ADA group were analyzed. In BS patients, IFX and ADA were both effective in improving uveitic macular edema (UME). ADA improved UME in BS but not in sarcoidosis patients. The efficacy of ADA in reducing doses of corticosteroids and glaucoma medications was better in sarcoidosis than in the BS group. CONCLUSION: Both IFX and ADA are efficacious in improving UME in BS patients. The reason that ADA improves UME better in BS than in sarcoidosis may be due to the difference in pathogenesis between these diseases.

The structure of a new cardenolide diglycoside and the biological activities of eleven cardenolide diglycosides from Nerium oleander.

A new cardenolide diglycoside (1) was isolated from Nerium oleander together with ten known cardenolide diglycosides 2-11. The structure of compound 1 was established on the basis of their spectroscopic data. The in vitro anti-inflammatory activity of compounds 1-11 was examined on the basis of inhibitory activity against the induction of the intercellular adhesion molecule-1 (ICAM-1). Compounds 2-5 were active at an IC(50) value of less than 0.8 µM. The cytotoxicity of compounds 1-11 was evaluated against three human cell lines normal human fibroblast cells (WI-38), malignant tumor cells induced from WI-38 (VA-13), and human liver tumor cells (HepG2). Compound 3 was active toward VA-13 cells, and compounds 2-5 were active toward HepG2 cells at IC(50) values of less than 1.3 µM. The multidrug resistance (MDR)-reversal activity of compounds 1-11 was evaluated on the basis of the amount of calcein in MDR human ovarian cancer 2780AD cells in the presence of each compound. Compounds 1 and 8 showed moderate effects on calcein accumulation.

Three new cardenolides from methanol extract of stems and twigs of Nerium oleander.

Two new cardenolide monoglycosides, cardenolides B-1 (1) and B-2 (2) were isolated from Nerium oleander, together with oleagenin (3) which is the first isolated compound from natural sources. The structure of compounds 1-3 were established on the basis of their spectroscopic data.

[Pars plana vitrectomy in patients with acute retinal necrosis syndrome: surgical results in 52 patients].

PURPOSE: To analyze results of pars plana vitrectomy for acute retinal necrosis (ARN) syndrome. METHODS: We reviewed the records of 52 eyes with ARN syndrome who underwent pars plana vitrectomy at the Tokyo Medical University Hospital from 1989 to 2007. The mean age was 50.1 +/- 10.2 years and the mean follow-up duration was 75.3 months. The causative virus was herpes simplex virus in 7 cases and varicella zoster virus in 45 cases. In all cases, treatment with acyclovir and corticosteroids was started from presentation. During the follow-up period, vitrectomy was done in patients who developed retinal detachment, and in those who developed posterior vitreous detachment exerting marked traction on the retina, even though retinal detachment had not occurred. In these cases, preoperative and postoperative visual acuities were compared and reoperation, retinal detachment preventive surgery and age-stratified visual prognosis after vitrectomy were analyzed. RESULTS: Visual acuity was improved by 2 lines or more in 13 eyes (25.0%), remained unchanged in 16 eyes (30.8%), and deteriorated by 2 lines or more in 23 eyes (44.2%). Thirty-seven of 52 eyes (71.2%) required re-operation. No significant differences were detected when the patients were stratified according to whether they were treated either with or without combined use of silicon oil, or according to whether they were treated either with or without prophylactic surgery for retinal detachment, as well as by age of vitrectomy. A combination of lens extraction, silicon oil and encircling sclera buckling procedure was associated with a significantly higher frequency of final visual acuity. CONCLUSION: Despite the advances in vitrectomy achieved today, the visual prognosis of acute retinal necrosis remains unsatisfactory. The present study found no significant improvement in the prognostic relevance of prophylactic vitrectomy. Improvement in pharmacotherapy may help improve the prognosis. Further prospective large-scale studies to compare other treatment modalities are also required.

Biphenylene-substituted ruthenocenylphosphine for Suzuki-Miyaura coupling of sterically hindered aryl bromides.

A highly general, active, and stable catalytic system was realized in the palladium-catalyzed Suzuki-Miyaura reactions of sterically hindered aryl bromides with arylboronic acids using biphenylene-substituted di-tert-butylruthenocenylphosphine (R-Phos) as a supporting ligand.

The application of the mutated acetolactate synthase gene from rice as the selectable marker gene in the production of transgenic soybeans.

We investigated selective culturing conditions for the production of transgenic soybeans. In this culturing system, we used the acetolactate synthase (ALS)-inhibiting herbicide-resistance gene derived from rice (Os-mALS gene) as a selectable marker gene instead of that derived from bacteria, which interfered with the cultivation and practical usage of transgenic crops. T(1) soybeans grown from one regenerated plant after selection of the ALS-targeting pyrimidinyl carboxy (PC) herbicide bispyribac-sodium (BS) exhibited herbicide resistance, and the introduction and expression of the Os-mALS gene were confirmed by genetic analysis. The selective culturing system promoted by BS herbicide, in which the Os-mALS gene was used as a selectable marker, was proved to be applicable to the production of transgenic soybeans, despite the appearance of escaped soybean plants that did not contain the Os-mALS transgene.

Presumed Vogt-Koyanagi-Harada disease with unilateral ocular involvement: report of three cases.

AIM: To report three cases of presumed Vogt-Koyanagi-Harada (VKH) disease with unilateral ocular manifestations. METHODS: This retrospective study reviewed the long-term follow-up observations of three patients who attended the uveitis clinic at Tokyo Medical University Hospital. The patients were followed for 5-16 years with systemic clinical, ophthalmologic and laboratory examinations. Ophthalmoscopic findings, extraocular manifestations, visual acuity, and response to corticosteroid administration were evaluated. RESULTS: Three patients had characteristic clinical features of VKH involving only one eye, including diffuse choroiditis, serous retinal detachment, focal areas of delayed choroidal perfusion, multifocal areas of pinpoint leakage, macular oedema, and optic nerve staining. All patients received systemic corticosteroid therapy during the acute phase of the disease. During the follow-up period (5-16 years), all three patients developed sunset-glow fundus and nummular chorioretinal depigmented scars in the affected eye only, as well as systemic complications of deafness, vitiligo, and poliosis. CONCLUSION: The clinical and laboratory features of all three patients were typical of VKH disease except for the unilateral involvement. It is important for ophthalmologists to recognize unilateral VKH disease, even though it is a rare clinical variant of the disease.

An unusual case of Behcet disease with posterior scleritis: A case report.

RATIONALE: Posterior scleritis is an ocular inflammatory disorder that can be associated with both infectious and non-infectious immune reactions. Behcet disease is a chronic, relapsing, multisystemic inflammatory disorder with uveitis. There are no reported cases of posterior scleritis with Bechet disease. PATIENT CONCERNS: A 50-year-old man previously diagnosed with systemic Behcet disease presented with ocular pain and decreased vision in the left eye. DIAGNOSIS: Posterior scleritis associated with Behcet disease was diagnosed based on optical coherence tomography showing choroidal folds, as well as contrast computed tomography and ultrasound sonography demonstrating thickening of the posterior sclera. INTERVENTIONS: Treatment with systemic corticosteroids was initiated. Since inflammation relapsed during steroid tapering, anti-tumor necrosis factor-alpha (TNF-α) therapy was used in combination, and tapering of steroids was possible without recurrence of inflammation for 12 months. OUTCOMES: Posterior scleritis was resolved and visual acuity improved. With the continuation of TNF-α therapy, oral prednisolone was successfully tapered and discontinued. No relapse of inflammation was observed at follow-up 1 year after discontinuation of prednisolone. LESSONS: Ophthalmologists should be aware of the possibility of rare manifestation of posterior scleritis in patients with Behcet disease, and that combined use of systemic steroids and anti-TNF-α therapy may resolve the scleritis without recurrence of inflammation.

Bid truncation mediated by caspases-3 and -9 in vinorelbine-induced apoptosis.

Vinorelbine is a chemotherapeutic vinca alkaloid clinically prescribed for non-small cell lung cancer and breast cancer. Here we studied the mechanism for vinorelbine-induced apoptosis in a human T-cell lymphoma. Although vinorelbine induces DNA fragmentation that is inhibited by specific peptide inhibitors for caspases-9 and -3 in Jurkat cells, caspase-8 deficiency retards vinorelbine-induced apoptosis. Activation of caspase-8 is also observed in vinorelbine-treated cells, and the activity is diminished when the caspase-3 activity is blocked by a specific peptide inhibitor, Ac-DNLC-CHO. Blocking of the Fas receptor with an antagonistic anti-Fas antibody does not affect vinorelbine-induced DNA fragmentation. These results suggest that vinorelbine-induced apoptosis is enhanced by the activation of caspase-8 via caspase-9-mediated activation of caspase-3, but not through a Fas-triggered signal. Western blotting suggests that vinorelbine cleaves caspase-3, -9 and -8 and reduces the amount of mitochondrial cytochrome c. Caspase-8 deficiency suppresses all of these events. A downstream substrate for caspase-8, Bid, is also cleaved in vinorelbine-treated cells, but the Bid truncation is also observed in caspase-8-deficient Jurkat cells. Importantly, recombinant caspases-3 and -9, as well as caspase-8, directly cleaves recombinant Bid in vitro. These results suggest that caspases-3 and -9 participate in Bid truncation, indicating a new mechanism for vinorelbine-induces apoptosis.

Confinement loss evaluation based on a multilayer division method in Bragg fibers.

Confinement loss is comprehensively evaluated for TE, TM, and hybrid modes of Bragg fibers using a multilayer division method newly developed. We show the loss dependence on the core radius, wavelength, cladding index contrast, and the number of cladding pairs. The confinement loss is reduced in proportion to (a/b)(2N) and (n(2) (b)b/n(2) (a)a)(2N) for the TE and other three modes, respectively, with respect to cladding pairs N under the quarter-wave stack condition, with cladding high na and low indices nb and their corresponding thicknesses a and b. For sufficiently large core radius, the confinement loss decreases in inverse proportion to the third and first powers of core radius for the TE and other three modes, respectively. Low loss modes are the TE(01), TE(02), HE(13), and TE(03) modes in order of increasing confinement loss.

Biphenylene-substituted ruthenocenylphosphine for Suzuki-Miyaura coupling of aryl chlorides.

High activity in the palladium-catalyzed Suzuki-Miyaura reactions of aryl chlorides with arylboronic acids was furnished using biphenylene-substituted di- tert-butylruthenocenylphosphine (R-Phos) as a supporting ligand. Substrate combinations even for the construction of highly hindered tetra- ortho-substituted biaryls can be achieved in good to excellent yields with low catalyst loadings in short reaction times.

Intravitreal injection of Tacrolimus (FK506) suppresses ongoing experimental autoimmune uveoretinitis in Rats.

AIM: To determine whether intravitreal injection of tacrolimus suppresses ongoing experimental autoimmune uveoretinitis (EAU) in rats. METHODS: Rats were immunised with interphotoreceptor retinoid-binding protein peptide (R14) and given an intravitreal injection of tacrolimus on day 12 after immunisation. Intraocular inflammation was assessed by slit-lamp biomicroscopy and histopathological examination. Interferon gamma and tumour necrosis factor alpha protein levels in the ocular tissues were measured. Gene expression of chemokines was determined in ocular tissues by reverse transcription-polymerase chain reaction. To evaluate the systemic effect of intravitreal injection of tacrolimus, delayed-type hypersensitivity was measured by ear swelling. RESULTS: Clinical and pathological scores showed that ocular inflammation of tacrolimus-treated eyes was markedly less than that of vehicle-treated eyes. The amount of interferon gamma and tumour necrosis factor alpha was considerably inhibited in tacrolimus-treated eyes. The gene expression of monocyte chemattractant protein-1 (MCP-1) and regulated upon activation, normal T cell expressed and secreted (RANTES) was markedly reduced in tacrolimus-treated eyes. Delayed-type hypersensitivity responses were not impaired in tacrolimus-treated rats. CONCLUSIONS: Intravitreal injection of tacrolimus was highly effective in suppressing the ongoing process of EAU without any side effects on systemic cellular immunity. This treatment may be useful in the management of patients with severe uveitis.

Fracture of Ni-Ti superelastic alloy under sustained tensile load in physiological saline solution containing hydrogen peroxide.

The fracture of Ni-Ti superelastic alloy has been investigated by a sustained tensile-loading test in physiological saline solution containing hydrogen peroxide (0.15M NaCl + 0.3M H(2)O(2)). The fracture always occurs when the applied stress exceeds the critical stress for martensite transformation. In contrast, under a low applied stress, the fracture does not always occur within 1000 h. The fracture is probably mainly caused by localized corrosion associated with the preferential dissolution of nickel ions. In 0.3M H(2)O(2) solution without NaCl, the fracture does not occur even under a high applied stress. The results of the present study imply that one reason for the fracture of the Ni-Ti superelastic alloy in vivo is localized corrosion due to the synergistic effects of hydrogen peroxide and sodium chloride under applied stress.

A case of hypertensive keratouveitis with endotheliitis associated with cytomegalovirus.

AIM: While cytomegalovirus is well known as a pathogenic organism of retinitis, especially associated with human immunodeficiency virus infection, there are few reports of anterior uveitis associated with cytomegalovirus. METHODS: The authors present a case of keratouveitis associated with cytomegalovirus. RESULTS: A 70-year-old Japanese man was referred to the authors because of poorly controlled hypertensive keratouveitis in the left eye. The patient had a history of recurrent hypertensive anterior uveitis. At presentation, the corneal stroma was edematous, with Descemet's folds and pigmented keratic precipitates. The anterior chamber angle was depigmented compared to the fellow eye. Even though pupil dilation and posterior synechiae were absent, iris atrophy was not evident. His right eye appeared normal except for moderate cataract. Funduscopy of the left eye was hazy, with the optic disc showing a normal color but poorly defined details, and no apparent exdative retinitis. The best-corrected decimal visual acuity of the right and left eyes was 0.4 and 0.02, respectively. Intraocular pressure was 11 mmHg in the right eye and 35 mmHg in the left, despite maximum medical therapy. Systemic acyclovir and prednisolone for a month did not improve the hypertensive keratouveitis. The aqueous humor was investigated for herpes simplex virus, varicella-zoster virus and cytomegalovirus. Cytomegalovius genome was detected by polymerase chain reaction analysis. Oral valganciclovir rapidly reduced ocular hypertension within a week. CMV DNA disappeared 3 months after the initiation of valganciclovir. CONCLUSION: The authors reported a case of hypertensive keratouveitis with endotheliitis associated with cytomegalovirus.

Molecular and Serological Characterization of Cucumber mottle virus, a New Cucurbit-Infecting Tobamo-like Virus.

A new tobamo-like virus was isolated from a greenhouse-grown cucumber that showed severe mosaic distortion on leaves and fruit, in the southern part of Japan. The virus was tentatively designated Cucumber mottle virus (CuMoV) and further characterized. The size and antigenicity of the coat protein (CP) and the complete sequence of the genome were compared with those of the known cucurbit-infecting tobamoviruses: the W and SH strains of Cucumber green mottle mosaic virus (CGMMV), the C and Y strains of Kyuri green mottle mosaic virus (KGMMV), Cucumber fruit mottle mosaic virus (CFMMV), and Zucchini green mottle mosaic virus (ZGMMV). The CP of CuMoV migrated more slowly than those of CGMMV-W and -SH and KGMMV-C and -Y in sodium dodecyl sulfate polyacrylamide gel electrophoresis. In Western blot analysis, the CP of CuMoV cross-reacted weakly with antisera against CGMMV-W and did not react with antisera against KGMMV-Y. The overall nucleotide sequence of CuMoV had 62.5 to 63.5% identity with those of CGMMV-W, -SH, KGMMV-Y, CFMMV, and ZGMMV. The genome organization was characteristic of tobamoviruses, encoding a 131-kb protein, a 188-kb protein, a movement protein (MP), and CP in 5' to 3' order. In the phylogenetic analyses of the CP, CuMoV was placed in a separate lineage from CGMMV-W, -SH, KGMMV-C, -Y, CFMMV, and ZGMMV. The results indicate that CuMoV is a distinct tobamovirus species which represents a third sub-subgroup in the cucurbit-infecting tobamoviruses.

Hydrogen absorption of titanium and nickel-titanium alloys during long-term immersion in neutral fluoride solution.

Hydrogen absorption of biomedical titanium and Ni-Ti alloys in a neutral fluoride (2.0% NaF) solution for up to 10,000 h at 37 degrees C has been evaluated by means of hydrogen thermal desorption analysis. For alpha titanium (commercial pure titanium), the amount of absorbed hydrogen was, at most, 10-30 mass ppm, and the corrosion product and hydride formation were revealed on the surface of the specimen by X-ray diffraction analysis. Ni-Ti superelastic alloy absorbed approximately 150 mass ppm of hydrogen, which was probably sufficient to result in the pronounced degradation of the mechanical properties, although corrosion was hardly observed. In contrast, hydrogen absorption of alpha-beta titanium (Ti-6Al-4V) and beta titanium (Ti-11.3Mo-6.6Zr-4.3Sn) alloys was negligible, although general corrosion was observed. The results of the present study indicate that the susceptibility of titanium and Ni-Ti alloys to hydrogen absorption in the neutral fluoride solution is different from that in the acidic fluoride solution reported previously.

Hydrogen embrittlement of work-hardened Ni-Ti alloy in fluoride solutions.

Hydrogen embrittlement of work-hardened Ni-Ti alloy has been examined in acidulated phosphate fluoride (APF) solutions. Upon immersion in a 2.0% APF solution with a pH of 5.0, tensile strength decreased markedly with immersion time. Moreover, the fracture mode changed from ductile to brittle due to brittle layer formation at the peripheral part of the cross section of the specimen. The amount of absorbed hydrogen increased linearly with immersion time, and it reached above 5000 mass ppm after 24 h. The hydrogen desorption temperature of the immersed specimens shifted from 450 degrees C to a lower temperature with immersion time. As the amount of absorbed hydrogen was larger than 500 mass ppm, the degradation of mechanical properties was recognized. Although the tensile properties and fracture mode scarcely change in a 0.2% APF solution, the slight reduction in hardness and hydrogen absorption of several hundreds mass ppm were observed. The results of the present study imply that work-hardened Ni-Ti alloy is less sensitive to hydrogen embrittlement compared with Ni-Ti superelastic alloy.

Suspected simultaneous bilateral anterior ischemic optic neuropathy in a patient with Behçet's disease.

AIM: To report a 47-year-old Japanese woman with a one-year history of Behçet's disease who complained of sudden bilateral visual loss with concurrent anterior ischemic optic neuropathy (AION). CASE REPORT: The patient's Snellen visual acuity was 0.1 (OD) and 0.3 (OS) of onset. There was bilateral mild anterior chamber inflammation. Bilateral optic disc pale swelling was observed without retinal exudates and edema. Fluorescein angiography demonstrated bilateral hypofluorescence of the optic disc in early frames but with no distinct retinal vasculitis. Visual field showed bilateral relative central scotoma and right altitudinal hemianopsia. Laboratory examination revealed an ESR of 26 mm in the first hour with a C-reactive protein level of < 0.3 mg/dl. Periocular injection of triamcinolone acetonide in both eyes without systemic corticosteroid administration improved her visual acuity to 0.7 (OD) and 1.2 (OS) within 45 days of onset. Bilateral optic disc swelling gradually resolved. In the early stages, fluorescein angiography demonstrated normal optic disc filling in both eyes. There was a residual right central scotoma on visual field. CONCLUSION: We observed an extremely rare case of simultaneous bilateral AION with Behçet's disease with marked visual recovery within 45 days of onset.

Hydrogen absorption behavior of beta titanium alloy in acid fluoride solutions.

Hydrogen absorption behavior of a beta titanium alloy in acid fluoride solutions has been analyzed by hydrogen thermal desorption. The amount of absorbed hydrogen increased with immersion time in a 2.0% acidulated phosphate fluoride (APF) solution. In the case of an immersion time of 60 h, the amount of absorbed hydrogen exceeded 10000 mass ppm. In contrast, the amount of hydrogen absorbed in the 0.2% APF solution was several times smaller than that in the 2.0% APF solution for the same immersion time. For immersion in a 0.2% APF solution, hydrogen absorption saturated after 48 h. The surface topography and corrosion products on the surface of the specimen immersed in the 2.0% APF solution were different from those in the 0.2% APF solution. During the later stage of immersion, the amount of absorbed hydrogen markedly increased under higher applied stress, although the applied stress did not enhance hydrogen absorption during the early stage of immersion. These results of hydrogen absorption behavior are consistent with the delayed fracture characteristics of the beta titanium alloy.