Two pairs of back-to-back α-helices of Kingella kingae RtxA toxin are crucial for the formation of a membrane pore.

The RtxA cytotoxin, a member of the RTX (Repeats in ToXin) family of pore-forming toxins, is the primary virulence factor of the paediatric facultative pathogen Kingella kingae. Although structure-function studies of RTX toxins have defined their characteristic domains and features, the exact membrane topology of RTX toxins remains unknown. Here, we used labelling of cell-bound RtxA with a membrane-impermeable, lysine-reactive reagent and subsequent detection of the labelled lysine residues by mass spectrometry, which revealed that most of the membrane-bound toxin is localised extracellularly.

PRIMARY OPEN-ANGLE GLAUCOMA DUE TO MUTATIONS IN THE MYOC GENE.

Aim: Mutations in the myocilin gene (MYOC) cause trabecular dysfunction and thus are involved in the pathogenesis of primary open-angle glaucoma (POAG). The aim of this study was to characterize and describe the clinical findings in two Czech families with POAG due to pathogenic variants in the MYOC gene.

Material And Methods: Members of the two families affected by POAG underwent complete ophthalmological examination.

The micronucleus cytome assay - A fast tool for DNA damage screening in human conjunctival epithelial cells.

Purpose: To assess whether the micronucleus cytome assay (MCyt) reliably detects DNA damage occurring in control and pathological superficial epithelial cells from human conjunctiva.

Methods: Impression cytology samples from the bulbar conjunctiva of 33 healthy controls, eight patients with conjunctival intraepithelial neoplasia (CIN) and eight with mucous membrane pemphigoid (MMP) were examined using the MCyt modified for the ocular surface.

Results: The mean number of micronuclei (MNi) in control samples was 0.

Acute elevation of intraocular pressure in patient with hyperlipidemic myeloma.

Purpose: To introduce a rare case of patient with hyperlipidemic myeloma and ocular manifestation in form of masquerade syndrome with acute elevation of intraocular pressure (IOP) and hyperviscous retinopathy.

Results: 55-year-old man with newly diagnosed hyperlipidemic myeloma and hyperviscous syndrome was acutely referred to our glaucoma outpatient clinic due to problems with his left eye: sudden pain, blurred vision, redness of the eye and IOP of 44 mm Hg. We excluded attack of angle closure glaucoma and found presence of whitish material in the anterior chamber and blood obstructing the iridocorneal angle.

The Lysosomal Sequestration of Tyrosine Kinase Inhibitors and Drug Resistance.

The Lysosomal sequestration of weak-base anticancer drugs is one putative mechanism for resistance to chemotherapy but it has never been directly proven. We addressed the question of whether the lysosomal sequestration of tyrosine kinase inhibitors (TKIs) itself contributes to the drug resistance in vitro. Our analysis indicates that lysosomal sequestration of an anticancer drug can significantly reduce the concentration at target sites, only when it simultaneously decreases its extracellular concentration due to equilibrium, since uncharged forms of weak-base drugs freely diffuse across cellular membranes.