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Myelin oligodendrocyte glycoprotein antibody-associated disease is a group of central nervous system demyelinating disorders caused by autoantibodies. While myelin oligodendrocyte glycoprotein antibody-associated disease typically presents as optic neuritis and myelitis in adults, this case report details a patient with brainstem lesions. A 45-year-old male presented with episodes of vertigo, nystagmus, and diplopia in left lateral gaze, which had persisted for 2 months, accompanied by headache. Computed tomography showed hyperdensity extending from the left side of the pons to the middle cerebellar peduncle. Magnetic resonance imaging revealed lesions exhibiting heterogeneous diffusion restriction, with enhancement that included granular and linear patterns. 18F-fluorodeoxyglucose positron emission tomography demonstrated increased uptake in these lesions. Following further evaluation, myelin oligodendrocyte glycoprotein antibody-associated disease was diagnosed. Treatment with high-dose corticosteroids initially alleviated symptoms, but symptoms flared upon reduction of the steroids. This case underscores the importance of considering myelin oligodendrocyte glycoprotein antibody-associated disease in the differential diagnosis of brainstem lesions and discusses distinguishing imaging features from similar conditions.

Abstract The development of the parathyroid and the thymus from the third pharyngeal pouch depends on the activities of the Gcm2 and Foxn1 transcription factors, respectively, whose expression domains sharply demarcate two regions in the developing third pharyngeal pouch. Here, we have generated novel mouse models to examine whether ectopic co-expression of Gcm2 in the thymic epithelium and of Foxn1 in the parathyroid perturbs the establishment of organ fates in vivo. Expression of Gcm2 in the thymic rudiment does not activate a parathyroid-specific expression programme, even in the absence of Foxn1 activity. Co-expression of Foxn1 in the parathyroid fails to impose thymopoietic capacity. We conclude that the actions of Foxn1 and Gcm2 transcription factors are cell context-dependent and that they each require permissive transcription factor landscapes in order to successfully interfere with organ-specific cell fate.

Homologous recombination plays a key role in the repair of double-strand breaks (DSBs), and thereby significantly contributes to cellular tolerance to radiotherapy and some chemotherapy. DSB repair by homologous recombination is initiated by 5' to 3' strand resection (DSB resection), with nucleases generating the 3' single-strand DNA (3'ssDNA) at DSB sites. Genetic studies of Saccharomyces cerevisiae demonstrate a two-step DSB resection, wherein CtIP and Mre11 nucleases carry out short-range DSB resection followed by long-range DSB resection done by Dna2 and Exo1 nucleases. Recent studies indicate that CtIP contributes to DSB resection through its non-catalytic role but not as a nuclease. However, it remains elusive how CtIP contributes to DSB resection. To explore the non-catalytic role, we examined the dynamics of Dna2 by developing an immuno-cytochemical method to detect ionizing-radiation (IR)-induced Dna2-subnuclear-focus formation at DSB sites in chicken DT40 and human cell lines. Ionizing-radiation induced Dna2 foci only in wild-type cells, but not in Dna2 depleted cells, with the number of foci reaching its maximum at 30 minutes and being hardly detectable at 120 minutes after IR. Induced foci were detectable in cells in the G2 phase but not in the G1 phase. These observations suggest that Dna2 foci represent the recruitment of Dna2 to DSB sites for DSB resection. Importantly, the depletion of CtIP inhibited the recruitment of Dna2 to DSB sites in both human cells and chicken DT40 cells. Likewise, a defect in breast cancer 1 (BRCA1), which physically interacts with CtIP and contributes to DSB resection, also inhibited the recruitment of Dna2. Moreover, CtIP physically associates with Dna2, and the association is enhanced by IR. We conclude that BRCA1 and CtIP contribute to DSB resection by recruiting Dna2 to damage sites, thus ensuring the robust DSB resection necessary for efficient homologous recombination.

Abstract Background  The pathogenesis of polypoidal choroidal vasculopathy (PCV), and even its clinical features, are controversial. Previous histopathological studies have identified different features; either dilated choroidal vessels or intra-Bruch’s neovascularization. These differences might be partly attributable to the influence of the disease stage. We therefore evaluated the clinical features of early and late stage PCV. Methods  The medical records of 110 eyes of 97 PCV patients were retrospectively reviewed. The time between the subjective onset of visual abnormality and examination at our clinic and the greatest linear dimension of the total lesion at the first examination were investigated. The period of disturbed vision and lesion size data were placed in ascending order to determine the first quartile point. Eyes with both values at or below the first quartile point were classified as ‘small–short’ (early stage). Eyes with both values equal to at least the third quartile point were classified as ‘large–long’ (late stage). Fundus photography, indocyanine green and fluorescein angiography, visual acuity, and clinical course were compared. Results  Twelve eyes from 12 patients were small-short cases (period of disturbed vision of 1 month or less, lesion size 2.0 disc diameters or less). Eleven eyes from ten patients were large-long cases (period of disturbed vision 36 months or more, lesion size at least 5.0 disc diameters). The large-long eyes were characterized by occult choroidal neovascular membrane or scar tissue secondary to exudative age-related macular degeneration. Noticeable in the small-short eyes were atrophic changes in the retinal pigment epithelium, choroidal vessel hyperpermeability and pulsation. The visual prognosis and clinical course were different between the groups. Conclusions  The difference of clinical features between the groups might reflect different disease stages, although not all of the features observed in the small-short group appeared to represent the early stages of those recorded in the large-long group. Thus, the variation in histopathologic features among previous reports might be partly attributable to differences in disease stage. [ABSTRACT FROM AUTHOR]