Type 2C protein phosphatases directly regulate abscisic acid-activated protein kinases in Arabidopsis

Abscisic acid (ABA) signaling is important for stress responses and developmental processes in plants. A subgroup of protein phosphatase 2C (group A PP2C) or SNF1-related protein kinase 2 (subclass III SnRK2) have been known as major negative or positive regulators of ABA signaling, respectively. Here, we demonstrate the physical and functional linkage between these two major signaling factors. Group A PP2Cs interacted physically with SnRK2s in various combinations, and efficiently inactivated ABA-activated SnRK2s via dephosphorylation of multiple Ser/Thr residues in the activation loop. This step was suppressed by the RCAR/PYR ABA receptors in response to ABA. However the abi1–1 mutated PP2C did not respond to the receptors and constitutively inactivated SnRK2. Our results demonstrate that group A PP2Cs act as ‘gatekeepers’ of subclass III SnRK2s, unraveling an important regulatory mechanism of ABA signaling.     

Successful therapy of macrophage activation syndrome with dexamethasone palmitate

Macrophage activation syndrome (MAS) is a severe and potential life-threatening complication of childhood systemic inflammatory disorders. Corticosteroids are commonly used as the first-line therapy for MAS. We report four patients with MAS who were successfully treated with dexamethasone palmitate (DexP), a liposome-incorporated dexamethasone, much more efficient than free corticosteroids. DexP effectively inhibited inflammation in MAS patients in whom the response to pulse methylprednisolone was not sufficient to manage their diseases. DexP was also effective as the first-line therapy for MAS. Based on these findings, DexP is an effective therapy in treating MAS patients.     

Antitumor Effect of Intratumoral Administration of Biological Response Modifiers: Induction of Immunosuppressive Acidic Protein, a Type of α1-Acid Glycoprotein, in Mice

The antitumor effects of biological response modifiers (BRMs) in an experimental mouse model, the "double grafted tumor system" were analyzed. Male BALB/c mice received simultaneous inoculations of Metn-A fibrosarcoma cells on the right flank (10⁶ cells) and left flank (2 × 10⁵ cells) on day 0, and BRMs were injected intratumorally into the right tumor on days 3, 4 and 5. PSK (a protein-bound polysaccharide preparation), interleuldn-1 (IL-1) and cepharanthin (R) cured not only the right, but also the left, non-treated tumor in a double grafted tumor system. OK-432 (a Streptococcus preparation) and BCG and tumor necrosis factor (TNF) cured the right tumor and inhibited the growth of the left tumor. Lentinan (a polysaccharide preparation) and IL-6 inhibited neither the right nor the left tumor. Immunosuppressive acidic protein (IAP) in serum was increased transiently soon after intradermal injection of PSK, CR, OK-432 and TNF in BALB/c mice. Lentinan, however, did not induce IAP. IAP in serum was gradually increased after intradermal inoculation of Meth-A tumor in BALB/c mice. The biochemical difference between PSK-induced IAP (early, inflammatory IAP) and Meth-A-induced IAP (late, tumor-induced IAP) was investigated by crossed affinity immunoelectrophoresis with concanavalin A. IAP of murine serum was separated into 4 peaks. IAP in normal mouse was rich in high-mannose type sugar chain (Peak 3) and contained no hybrid-type sugar chain (Peak 4), which was present in inflammatory and tumor-induced IAP. Inflammatory IAP was rich in biantennary sugar chain (Peak 2) and tumor-induced IAP was rich in tri-tetraantennary sugar chain (Peak 1).     

A case of glaucoma with choroidal hemangioma managed by nonpenetrating trabeculectomy

BACKGROUND: Nonpenetrating trabeculectomy was used in a patient with glaucoma complicated by diffuse choroidal hemangioma. CASE: A 12-year-old boy suffered from glaucoma with choroidal hemangioma in the left eye. Intraocular pressure was 28 mm Hg and visual acuity was 0.04. Nonpenetrating trabeculectomy was then performed. OBSERVATIONS: Postoperative intraocular pressure was controlled at around 15 mm Hg with pilocarpine hydrochloride eye drops. Visual acuity and visual field were preserved over 19 months after the operation. CONCLUSIONS: An increase in aqueous outflow resistance was considered to be the major mechanism in the rise in intraocular pressure, based on distinct dilatation and tortuosity of the episcleral blood vessels and congestion of Schlemm's canal. Therefore, construction of aqueous drainage by nonpenetrating trabeculectomy was effective. Retaining the trabecular meshwork was also considered effective in controlling complications such as choroidal hemorrhage and postoperative flat anterior chamber.     

Accumulation of photosensitizer ATX-S10 (Na) in experimental corneal neovascularization

PURPOSE: To determine the most appropriate time for laser irradiation to produce selective occlusion of new corneal vessels by photodynamic therapy (PDT) with a new photosensitizer, ATX-S10(Na). METHODS: The time course of the plasma levels of ATX-S10(Na) and the degree of dye accumulation in the corneal neovascularization after intravenous administration was determined in rabbit eyes. Plasma concentration of ATX-S10(Na) was analyzed by a spectrophotometer. The amount of ATX-S10(Na) in the new corneal vessels was measured by nitrogen-pulsed laser spectrofluorometry. Frozen sections of neovascularized cornea and iris were observed by fluorescence microscopy. RESULTS: Plasma ATX-S10(Na) concentration was highest 5 minutes after dye injection and rapidly decreased and reached almost zero at 24 hours, indicating its prompt excretion from the body. The amount of ATX-S10(Na) in the new corneal vessels as measured by nitrogen-pulsed laser spectrofluorometry increased and reached maximal level at 2 to 4 hours. Under fluorescence microscopy, the dye was more abundantly localized in the wall of new corneal vessels than in the normal tissue at 2 to 4 hours. CONCLUSION: These results indicate that laser irradiation between 2 and 4 hours after dye injection is appropriate for selective PDT with ATX-S10(Na) for the occlusion of new corneal vessels.     

A retrospective pilot study of indocyanine green enhanced diode laser photocoagulation for subfoveal choroidal neovascularization associated with age-related macular degeneration

PURPOSE: The effectiveness and limitations of indocyanine green (ICG) enhanced diode laser photocoagulation in treating subfoveal choroidal neovascularization (CNV) associated with age-related macular degeneration (AMD) were investigated retrospectively. METHODS: Thirty-eight eyes of 37 patients with subfoveal CNV received ICG enhanced diode laser (wavelength, 805 nm) photocoagulation in our preliminary series. Nineteen eyes had classic CNV and the others had occult CNV, which was well-delineated on ICG angiography. The rate of anatomical success and functional outcomes were investigated. Factors prognostic of a final visual acuity of 0.1 or better were analyzed. The follow-up period ranged from 6 to 51 months (mean +/- SD = 26.5 +/- 14.4 months). RESULTS: Occlusion of CNV was achieved in 35 of 38 eyes (92%), and 7 eyes (18%) showed recurrence, which was occluded by retreatment in all but 1 eye. Ten eyes (26.3%) showed improvement of visual acuity; 16 (42.1%) showed no change; and in 12 eyes (31.6%) visual acuity deteriorated. Factors prognostic of a final visual acuity of 0.1 or better were good preoperative visual acuity (Mann-Whitney U-test, P =.0028), and a relatively short distance between the edge of laser burns and the center of the foveal avascular zone (unpaired t-test, P =.0285). CONCLUSION: Indocyanine green enhanced photocoagulation achieved a higher anatomical success rate but functional outcomes equal to those with argon or krypton laser photocoagulation. A controlled prospective study is necessary to prove the efficacy of this treatment.     

Management of orbital lymphangioma using intralesional injection of OK-432

AIM: To treat orbital lymphangioma with an intralesional injection of OK-432 (group A Streptococcus pyogenes of human origin). METHOD: A 14 year old boy had a right orbital cystic lymphangioma. The visual acuity in the eye was 20/28. In an initial treatment, 0.02 mg of OK-432, was injected into the tumour after aspiration of the fluid contents, but no effect was seen. The second treatment was performed with 0.04 mg of OK-432. RESULT: 4 months later, the lesion had totally shrunk to fibrous tissue. The side effects were fever, a local inflammatory reaction lasting 3 days, and increased intraocular pressure, which was managed by draining the fluid contents. Visual acuity improved to 20/15, and the visual field defect and restriction of eye movement seen before treatment disappeared. No recurrence was noted 1 year after treatment. CONCLUSION: An intralesional injection of OK-432 shrunk the lymphangioma without functional disturbance and scar in the facial skin. OK-432 may be useful for orbital lymphangioma, but further studies are still warranted to determine efficacy, complications, and the optimal dose for safe treatment.