Regulation of RKIP Function by Helicobacter pylori in Gastric Cancer

Helicobacter pylori (H. pylori) is a gram-negative, spiral-shaped bacterium that infects more than half of the world’s population and is a major cause of gastric adenocarcinoma. The mechanisms that link H. pylori infection to gastric carcinogenesis are not well understood. In the present study, we report that the Raf-kinase inhibitor protein (RKIP) has a role in the induction of apoptosis by H. pylori in gastric epithelial cells. Western blot and luciferase transcription reporter assays demonstrate that the pathogenicity island of H. pylori rapidly phosphorylates RKIP, which then localizes to the nucleus where it activates its own transcription and induces apoptosis. Forced overexpression of RKIP enhances apoptosis in H. pylori-infected cells, whereas RKIP RNA inhibition suppresses the induction of apoptosis by H. pylori infection. While inducing the phosphorylation of RKIP, H. pylori simultaneously targets non-phosphorylated RKIP for proteasome-mediated degradation. The increase in RKIP transcription and phosphorylation is abrogated by mutating RKIP serine 153 to valine, demonstrating that regulation of RKIP activity by H. pylori is dependent upon RKIP’s S153 residue. In addition, H. pylori infection increases the expression of Snail, a transcriptional repressor of RKIP. Our results suggest that H. pylori utilizes a tumor suppressor protein, RKIP, to promote apoptosis in gastric cancer cells

Severe Leber Hereditary Optic Neuropathy Plus Disease in a Middle-Aged Man

A 50-year-old African American man with hypertension, atrial fibrillation, and congestive heart failure presented with progressive vision loss in both eyes over 3 months. He described blurriness and dimming of vision and changes in color perception. The patient also endorsed ascending numbness and paresthesias from his feet to hips bilaterally, with an onset 6 months before vision loss

Getting Stoned From Being Too High: Accidental Discovery That Optic Disc Drusen May Arise From High Intracranial Pressure of Pseudotumor Cerebri / Idiopathic Intracranial Hypertension (.pdf)

To evaluate the prevalence of optic disc drusen (ODD) in the setting of papilledema from pseudotumor cerebri/idiopathic intracranial hypertension (IIH), and to assess if the coexistence of both conditions may worsen the visual outcomes as compared with either condition alone

Risk Factors for Corneal Striae in Eyes after Glaucoma Surgery

Eyes with corneal striae had steeper cornea, induced astigmatism, and higher corneal hysteresis (CH), which implies a relationship between striae, corneal shape, and the cornea's resistance to deformation at low intraocular pressures (IOPs). Anterior corneal striae (ACS) are associated with low IOP. However, the clinical significance of ACS is unclear. Here, we aim to evaluate differences in eyes with striae compared with eyes without striae. Adults with ACS (cases) and without ACS (controls) ≥8 weeks after glaucoma surgery with an IOP ≤10 mm Hg were enrolled. Optical coherence tomography and optical biometry were performed. CH, defined as the difference in pressure between corneal indentation and reformation in response to an air jet, was obtained by the ocular response analyzer. Hypotony maculopathy (HM) was defined as optic disc swelling, vascular tortuosity attributed to hypotony, or clinical presence of chorioretinal folds confirmed on OCT. One hundred sixteen eyes (76 cases, 40 controls) were included. Cases had a lower IOP compared with controls (6.5±2.3 vs. 8.5±1, P<0.0001). A 1 mm Hg increase in CH increased ACS odds [odds ratio (OR)=1.51, P=0.01]. A 1 D increase in the flattest presurgical and postsurgical corneal power increased ACS odds by 1.83 (P=0.01) and 1.41 (P=0.02), respectively. Astigmatism increased in eyes with ACS by 1.11 D (P<0.001). ACS odds were increased with every 1 minute increase in mitomycin-C duration (OR=1.58, P=0.047) and decreased with the use of topical glaucoma medication (OR=0.62, P=0.03). Visual acuity decreased from logarithm of the minimal angle of resolution 0.22 (20/33 Snellen) presurgery to 0.28 (20/38) postsurgery (P=0.008), independent of ACS. HM occurred in 19% of cases (P=0.05). A higher postsurgical CH increased HM odds (OR=1.8, P=0.003). HM predicted a 0.41 mm decrease in axial length (P<0.0001), independent of IOP. ACS were associated with a steeper cornea, induced astigmatism, and higher CH, suggesting a relationship between striae, corneal shape, and the cornea's ability to resist deformations at lower IOP. CH, HM, and axial length shortening were associated independently of IOP

IL-6 promotes RKIP and STAT 3 transcription and phosphorylation; <i>H. pylori</i> infection induces STAT3 transcription and phosphorylation.

<p>(A) Western blot analysis of AGS cells treated with the indicated concentrations of IL-6 and for 6 hours. Densitometry was performed and for pRKIP expression, our results indicate a 1.8 fold incerase of pRKIP (average intensity 0.59 vs 1.051) in cells treated with 25 ng/ml IL-6 and a 1.35 fold increase (average intensity 0.59 vs 0.772) in cells treated with 50 ng/ml IL-6. For RKIP expression, our results indicate a 0.8 fold incerase of pRKIP (average intensity 0.69 vs 0.563) in cells treated with 25 ng/ml IL-6 and a 1.05 fold increase (average intensity 0.69 vs 0.745) in cells treated with 50 ng/ml IL-6 when normalized to actin at each time point. (B) Western blot analysis of AGS co-cultured with <i>H. pylori</i> and examined for pY705 STAT3 for the indicated times; (C) STAT3 luciferase reporter transcriptional assay of AGS cells co-cultured with <i>H. pylori</i> at the indicated MOI; (D) STAT3 luciferase reporter assay of AGS cells transiently transfected with STAT3 for 24 h and co-cultured with <i>H. pylori</i> and/or treated with IL-6 for 6 h. A paired t-test was performed to analyze the increase or decrease in STAT3 transcription of experimental samples when compared to empty vector (EV): *IL-6, p<0.0003; **STAT3, p<0.009; *** <i>H. pylori</i> p<0.0005; **** STAT3 and <i>H. pylori</i> p<0.0000023.</p