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

A genome-wide association study of cleft lip with and without cleft palate identifies risk variants near MAFB and ABCA4

Case-parent trios were used in a genome-wide association study of cleft lip with and without cleft palate. SNPs near two genes not previously associated with cleft lip with and without cleft palate (MAFB, most significant SNP rs13041247, with odds ratio (OR) per minor allele = 0.704, 95% CI 0.635-0.778, P = 1.44 × 10-11; and ABCA4, most significant SNP rs560426, with OR = 1.432, 95% CI 1.292-1.587, P = 5.01 × 10-12) and two previously identified regions (at chromosome 8q24 and IRF6) attained genome-wide significance. Stratifying trios into European and Asian ancestry groups revealed differences in statistical significance, although estimated effect sizes remained similar. Replication studies from several populations showed confirming evidence, with families of European ancestry giving stronger evidence for markers in 8q24, whereas Asian families showed stronger evidence for association with MAFB and ABCA4. Expression studies support a role for MAFB in palatal development. © 2010 Nature America, Inc. All rights reserved