CK2 Phosphorylates Sec31 and Regulates ER-To-Golgi Trafficking

Protein export from the endoplasmic reticulum (ER) is an initial and rate-limiting step of molecular trafficking and secretion. This is mediated by coat protein II (COPII)-coated vesicles, whose formation requires small GTPase Sar1 and 6 Sec proteins including Sec23 and Sec31. Sec31 is a component of the outer layer of COPII coat and has been identified as a phosphoprotein. The initiation and promotion of COPII vesicle formation is regulated by Sar1; however, the mechanism regulating the completion of COPII vesicle formation followed by vesicle release is largely unknown. Hypothesizing that the Sec31 phosphorylation may be such a mechanism, we identified phosphorylation sites in the middle linker region of Sec31. Sec31 phosphorylation appeared to decrease its association with ER membranes and Sec23. Non-phosphorylatable mutant of Sec31 stayed longer at ER exit sites and bound more strongly to Sec23. We also found that CK2 is one of the kinases responsible for Sec31 phosphorylation because CK2 knockdown decreased Sec31 phosphorylation, whereas CK2 overexpression increased Sec31 phosphorylation. Furthermore, CK2 knockdown increased affinity of Sec31 for Sec23 and inhibited ER-to-Golgi trafficking. These results suggest that Sec31 phosphorylation by CK2 controls the duration of COPII vesicle formation, which regulates ER-to-Golgi trafficking

Ocular infections caused by Providencia rettgeri

To report a series of patients with ocular infections caused by the rarely described gram-negative bacterium, Providencia rettgeri. Retrospective case series. Five patients with ocular infections who grew P. rettgeri after culture (2 keratitis, 1 dacryocystitis, 1 conjunctivitis, 1 conjunctivitis/endophthalmitis). Microbiology culture results positive for P. rettgeri were cross-referenced to identify the patients with ocular infections. Medical records of these patients were carefully reviewed. Descriptive analysis of each patient's history, potential risk factors, and clinical outcome. Five eyes in 2 institutions were found to be culture positive for the gram-negative bacterium P. rettgeri. The organism may cause keratitis, dacryocystitis, conjunctivitis, and endophthalmitis. Possible risk factors include a compromised ocular surface and coexisting medical morbidity, including urinary tract infections, recent hospitalizations, and an immunocompromised state. Culture and sensitivity profiles should guide treatment; resistant strains are being identified. Infections caused by P. rettgeri, although rare, are responsible for ocular morbidity. This report describes patient attributes, risk factors, and outcomes that will be helpful to ophthalmologists treating ocular infections. P. rettgeri should be acknowledged as a source of ocular infection

Immune cell subsets in necrotizing fasciitis: an immunohistochemical analysis

Current concepts of the pathophysiology of necrotizing fasciitis (NF), a life-threatening infection of soft tissues associated with a toxic shock syndrome, emphasizes the role of bacterial superantigens as mediators of cytokine release by immune lymphocytes. In order to assess the cellular basis of immune activation, immunohistochemistry was applied to the analysis of inflammatory cell subsets in situ in 13 patients with NF. The percentage of inflammatory cells in skin and soft tissue was scored from 0 to 3+ (>50%). Substantial numbers of CD15+ polymorphonuclear leukocytes were present in 12 of 13 patients. CD3+ T-lymphocytes accounted for >10%, CD68+ macrophages for >50%, and Factor XIIIa+ mononuclear cells for >10% of the mononuclear cell infiltrates, respectively, in 10 of 13 patients, whereas CD1a+ cells were present in only 3 of 13 cases and accounted for <10% of mononuclear inflammatory cells. We conclude that immune lymphocytes and accessory immune cells are represented in substantial numbers in the early lesions of NF, and their presence supports current concepts with respect to the pathophysiology of this disorder

Long-term Follow-up of Conjunctival and Corneal Intraepithelial Neoplasia Treated with Topical Interferon Alfa-2b

To evaluate the long-term recurrence rate (>1 year) of conjunctival and corneal intraepithelial neoplasia (CIN) treated with topical interferon alfa-2b. Retrospective, noncomparative, interventional case series. Twenty-eight eyes of 26 patients from 2 institutions, treated between April 1997 and June 2005, with CIN lesions utilized topical interferon alfa-2b drops 4 times daily until clinical resolution was achieved. Patients' charts and clinical photographs were reviewed, and data were analyzed. All eyes were monitored for the possibility of recurrence with a minimum of 1-year follow-up from the time of documented clinical resolution. Complete clinical resolution of the CIN lesions was achieved in 27 of the 28 eyes treated (96.4%). One of the 28 eyes treated (3.6%) had only a partial response to treatment. For the 27 eyes with complete response, resolution occurred after a median of 2.0 months (range, 10 days–15 months). Eyes were treated for a median of 3.2 months (range, 1–15). Median follow-up after clinical resolution (tumor-free period) was 42.4 months (range, 14–89). One eye of the 27 analyzed (3.7%) experienced a recurrence. Side effects of treatment were limited to mild conjunctival hyperemia and follicular conjunctivitis in 3 patients (12%). In all cases, there was total resolution of the side effects within 1 month after cessation of the medication. In this group of patients with CIN lesions observed for >1 year, topical interferon alfa-2b was effective in treating lesions with minimal self-limited side effects

Tuberculous Uveitis Presenting with a Bullous Exudative Retinal Detachment: A Case Report and Systematic Literature Review

<p><i>Purpose</i>: To describe tuberculous uveitis (TU) presenting as a bullous retinal detachment (RD) and to perform a comprehensive literature review on TU with similar features.</p> <p><i>Methods</i>: Observational case report and systematic literature review.</p> <p><i>Results</i>: An 84-year-old woman presented with bilateral granulomatous uveitis and bullous RD in the left eye. The interferon gamma release assay was strongly positive, but all other tests were unremarkable. The patient was diagnosed with TU and started on anti-tubercular therapy (ATT) and systemic steroids with excellent treatment response. Twenty-six articles (32 cases) reported TU with exudative RD. Choroidal tuberculoma was the most common clinical manifestation, followed by optic disc edema and retinal exudate. Systemic steroids with ATT improved vision in more patients (78.6%) than ATT alone (50.0%) or oral steroids followed by ATT (50.0%).</p> <p><i>Conclusion</i>: Atypical presentations of TU make diagnosis and treatment difficult. A high level of suspicion for TU is needed to minimize ocular morbidity.</p

Femtosecond laser-assisted sutureless anterior lamellar keratoplasty.

To report the technique and small case series results of femtosecond laser-assisted sutureless anterior lamellar keratoplasty (FALK) for anterior corneal pathology. Retrospective, noncomparative, interventional case series. Twelve consecutive eyes from 12 patients with anterior corneal scarring. Femtosecond laser-assisted sutureless anterior lamellar keratoplasty. Measured parameters included femtosecond laser settings, technique, uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), and complications. Mean follow-up was 12.7 months (range, 6-24). No intraoperative complications were found. Uncorrected visual acuity (VA) improved in 7 eyes (58.3%) compared with preoperative VA. The mean difference between preoperative and postoperative UCVAs was a gain of 2.5 lines (range, unchanged-7 lines). Best-corrected VA was unchanged or improved in all eyes compared with preoperative levels. The mean difference between preoperative and postoperative BCVAs was a gain of 3.8 lines (range, unchanged-8 lines). In 2 eyes, adjuvant surgical procedures were performed (one treated with phototherapeutic keratectomy and the other with photorefractive keratectomy). Six patients (50%) developed dry eye after FALK, which improved during the follow-up period. No graft rejection, infection, or epithelial ingrowth was found in this series of patients. Femtosecond laser-assisted sutureless anterior lamellar keratoplasty could improve UCVA and BCVA in patients with anterior corneal pathology