A case of eosinophilic chronic rhinosinusitis associated with optic neuropathy

We report a case of eosinophilic chronic rhinosinusitis (ECRS) associated with optic neuropathy. The visual acuity in the right eye was suddenly reduced to no light perception on awakening in the morning. Fundus examination of both eyes on the same day showed no remarkable changes. Emergency computed tomography showed pan-sinusitis bilaterally and a partial defect of the sphenoid bone on the right side. From the clinical findings, the case was diagnosed as optic neuropathy associated with chronic sinusitis. Endoscopic sinus surgery (ESS) was performed on the same day, and all of the major sinuses were found to be filled with highly viscous fluid. Part of the optic canal had a defect probably due to inflammatory invasion from the adjacent sphenoid bone. Steroid therapy was started immediately postoperatively. Histopathological examination of excised polyps showed that numerous eosinophils had invaded the polyps but no hyphae were present. The patient reported that he had bronchial asthma and had had nasal polypectomy. Six months after the ESS and steroid therapy, the patient had a recurrence of the sinusitis. At that time, laboratory examination showed an elevation of total IgE and eosinophil numbers. From the clinical findings and course, this case was diagnosed as ECRS accompanied by optic neuropathy. Although ECRS rarely has ocular complications, the inflammation can spread and the optic nerve can be affected

Orbital apex syndrome associated with herpes zoster ophthalmicus

We report our findings for a patient with orbital apex syndrome associated with herpes zoster ophthalmicus. Our patient was initially admitted to a neighborhood hospital because of nausea and loss of appetite of 10 days’ duration. The day after hospitalization, she developed skin vesicles along the first division of the trigeminal nerve, with severe lid swelling and conjunctival injection. On suspicion of meningoencephalitis caused by varicella zoster virus, antiviral therapy with vidarabine and betamethasone was started. Seventeen days later, complete ptosis and ophthalmoplegia developed in the right eye. The light reflex in the right eye was absent and anisocoria was present, with the right pupil larger than the left. Fat-suppressed enhanced T1-weighted magnetic resonance images showed high intensity areas in the muscle cone, cavernous sinus, and orbital optic nerve sheath. Our patient was diagnosed with orbital apex syndrome, and because of skin vesicles in the first division of the trigeminal nerve, the orbital apex syndrome was considered to be caused by herpes zoster ophthalmicus. After the patient was transferred to our hospital, prednisolone 60 mg and vidarabine antiviral therapy was started, and fever and headaches disappeared five days later. The ophthalmoplegia and optic neuritis, but not the anisocoria, gradually resolved during tapering of oral therapy. From the clinical findings and course, the cause of the orbital apex syndrome was most likely invasion of the orbital apex and cavernous sinus by the herpes virus through the trigeminal nerve ganglia

Visual field defects of optic neuritis in neuromyelitis optica compared with multiple sclerosis

<p>Abstract</p> <p>Background</p> <p>Neuromyelitis optica (NMO) is an inflammatory demyelinating disease that predominantly affects the optic nerves and the spinal cord, and is possibly mediated by an immune mechanism distinct from that of multiple sclerosis (MS). Central scotoma is recognized as a characteristic visual field defect pattern of optic neuritis (ON), however, the differing pathogenic mechanisms of NMO and MS may result in different patterns of visual field defects for ON.</p> <p>Methods</p> <p>Medical records of 15 patients with NMO and 20 patients with MS having ON were retrospectively analyzed. A thorough systemic and neurological examination was performed for evaluating ON. The total number of relapses of ON and visual fields was investigated. Visual fields were obtained by Goldmann perimeter with each ON relapse.</p> <p>Results</p> <p>All MS patients experienced central scotoma, with 90% of them showing central scotoma with every ON relapse. However, 53% of NMO patients showed central scotoma with every ON relapse (p = 0.022), and the remaining 47% of patients experienced non-central scotoma (altitudinal, quadrant, three quadrant, hemianopia, and bitemporal hemianopia). Thirteen percent of NMO patients did not experience central scotoma during their disease course. Altitudinal hemianopia was the most frequent non-central scotoma pattern in NMO.</p> <p>Conclusions</p> <p>NMO patients showed higher incidence of non-central scotoma than MS, and altitudinal hemianopia may be characteristic of ON occurring in NMO. As altitudinal hemianopia is highly characteristic of ischemic optic neuropathy, we suggest that an ischemic mechanism mediated by anti-aquaporin-4 antibody may play a role in ON in NMO patients.</p

Histone H2AX Phosphorylation Independent of ATM after X-irradiation in Mouse Liver and Kidney in situ

Histone H2AX undergoes phosphorylation at Ser-139 (gamma-H2AX) rapidly in response to DNA double-strand breaks (DSBs) induced by ionizing radiation. The post-translational modification of H2AX plays a central role in responses to radiation, including the repair of DSBs. Although ataxia telangiectasia mutated (ATM) kinase phosphorylates Ser-139 of H2AX in vitro, the post-translational modification pattern and the modifier of H2AX in organs in vivo are not yet well understood. In this study, we detected phosphorylation of H2AX at Ser-139 in cells of the mouse ear, liver, and kidney after X-irradiation. Moreover, the phosphorylation of H2AX was regulated depending on not only the cell type, but also the organ type and the localization of a cell type in an organ. Following X-irradiation, H2AX was phosphorylated in the liver and kidney of ATM gene knockout mice, suggesting that ATM kinase is not essential for phosphorylation of H2AX in these organs after X-irradiation in vivo

Tissue-specific DNA-PK-dependent H2AX phosphorylation and gamma-H2AX elimination after X-irradiation in vivo

Histone H2AX rapidly undergoes phosphorylation at Ser139 (gamma-H2AX) in response to DNA double-strand breaks. Although ATM kinase and DNA-PK phosphorylate Ser139 of H2AX in culture cells, the regulatory mechanism of gamma-H2AX level remains unclear in vivo. Here, we detected the phosphorylation of H2AX and the elimination of gamma-H2AX in the mouse skin after X-irradiation. Furthermore, following X-irradiation, the level of gamma-H2AX also increased in mice lacking either ATM or DNA-PK. Although the elimination after Xirradiation was detected in the skin of these mutant mice, the elimination in DNA-PK-deficient mice was slower than that in C3H and ATM knockout mice, suggesting that a fraction of gamma-H2AX in the skin is eliminated in a DNA-PK-dependent manner. Although the DNA-PK-dependent elimination of gamma-H2AX was also detected in the liver, kidney, and spleen, the DNA-PK-dependent phosphorylation of H2AX was detected in the spleen only. These results suggest that the regulatory mechanism of gamma-H2AX level is tissue- specific

p53 phosphorylation in mouse skin and in vitro human skin model by high-dose-radiation exposure

The skin is an eternal organ that is most frequently exposed to radiation. High-dose radiation initiates and promotes acute radiation injury. Thus, it is important to investigate the influence of high-dose radiation exposure on the skin at the molecular level. The post-translational modification of p53 plays a central role in radiation responses, including apoptosis and cell growth arrest. Although it is well known that ataxia telangiectasia mutated (ATM) kinase and DNA-dependent protein kinase (DNA-PK) can phosphorylate Ser15/Ser18 of p53 in vitro, the post-translational modification pattern and the modifier of p53 in the skin after exposure to high-dose X-rays are not yet well understood. Here we show that the phosphorylation of p53 on Ser15/Ser18, as well as the phosphorylation of histone H2AX on Ser139, was detected in the keratinocytes of the mouse skin and human skin models after high-dose X-ray irradiation. Following high-dose X-ray irradiation, both proteins were also phosphorylated in the skin keratinocytes of both ATM gene knockout mice and DNA-PK-deficient SCID mice

Dynamic change of histone H2AX phosphorylation independent of ATM and DNA-PK in mouse skin in situ.

Histone H2AX undergoes phosphorylation on Ser 139 (gamma-H2AX) rapidly in response to DNA double-strand breaks induced by exogenous stimuli, such as ionizing radiation. However, the endogenous phosphorylation pattern and modifier of H2AX remain unclear. Here we show that H2AX is regulated physically at the level of phosphorylation at Ser139 during a hair cycle in the mouse skin. In anagen hair follicles, gamma-H2AX-positive cells were observed in the outer root sheath (ORS) and hair bulb in a cycling inferior region but not in a permanent superficial region. In telogen hair follicles, gamma-H2AX-positive cells were only detected around the germ cell cap. In contrast, following X-irradiation, gamma-H2AX was observed in various cell types including the ORS cells in the permanent superficial region. Furthermore, gamma-H2AX-positive cells were detected in the skin of mice lacking either ATM or DNA-PK, suggesting that these kinases are not essential for phosphorylation in vivo

Dynamics of Ku80 in Living Hamster Cells with DNA Double-Strand Breaks Induced by Chemotherapeutic Drugs.

A variety of chemotherapeutic drugs, e.g., etoposide and bleomycin, are widely used in clinical practice to treat many types of animal malignancies. In the clinical situation, cellular resistance to chemotherapy is a significant component of tumor treatment failure. A variety of DNA repair factors, e.g., Ku80, might be a key contributor to chemoresistance to anticancer agents. In both cancer and normal cells, Ku80 plays a key role as a sensor of DNA double-strand break (DSB) induced by treatment with some chemotherapeutic drugs. Although the localization and mobility of Ku80 play a key role in regulating the physiological function of Ku80, it is not clear whether those of Ku80 are affected after treatment with chemotherapeutic drugs. We examined the localization and mobility of Ku80 in living hamster cells with or without DSBs, which were induced by treatment with chemotherapeutic drugs. Our data showed that Ku80, in contrast to H2AX, is highly mobile in the nuclei. We found that before and after the induction of DNA damage by treatment with etoposide or bleomycin, a major portion of Ku80 is exchanged by the same kinetics in the nuclei of interphase cells. These results suggest that the mobility of a major portion of Ku80 is not affected by DNA DSBs in order to find other DSBs. In addition, the information would be worthy to develop some new chemotherapeutic drugs to treat many types of animal malignancie