A Method to Measure Visual Field Sensitivity at the Edges of Glaucomatous Scotomata

METHODS. Subjects comprised 22 glaucomatous patients. Gradients of sensitivity were calculated for ''squares'' of test points in a patient's 24-2/30-2 VF results, so that the edges of scotomata could be identified where gradients were steep. Next, 10 new VF points were placed in these locations for each patient. Each patient's VF was then measured using this novel test grid (52 standard 24-2 test points and 10 additional points examined concurrently) on two separate occasions. The absolute difference between the measured sensitivity at each new additional test point and the average of the sensitivities of its surrounding four test points was calculated (D ave ). The intra-and intervisit reproducibility of the additional test points' thresholds was calculated. Finally, fluctuation of overall VF damage was estimated using the intraclass correlation coefficient (ICC) and the coefficient of variation (CV). RESULTS. The average of the sensitivities (D ave ) increased as the gradient of the plane steepened, whereas the reproducibility of the additional test points' thresholds remained stable. ICC was significantly higher and CV was significantly lower for the novel test grid compared with the standard 24-2 test pattern. CONCLUSIONS. It may be advantageous to increase the density of VF test points where there are large local differences in VF sensitivity. These additional measurements may result in more reproducible and well-defined estimates of scotomata

Erlotinib inhibits osteolytic bone invasion of human non-small-cell lung cancer cell line NCI-H292

Previous preclinical and clinical findings have suggested a potential role of epidermal growth factor receptor (EGFR) in osteoclast differentiation and the pathogenesis of bone metastasis in cancer. In this study, we investigated the effect of erlotinib, an orally active EGFR tyrosine kinase inhibitor (TKI), on the bone invasion of human non-small-cell lung cancer (NSCLC) cell line NCI-H292. First, we established a novel osteolytic bone invasion model of NCI-H292 cells which was made by inoculating cancer cells into the tibia of scid mice. In this model, NCI-H292 cells markedly activated osteoclasts in tibia, which resulted in osteolytic bone destruction. Erlotinib treatment suppressed osteoclast activation to the basal level through suppressing receptor activator of NF-κB ligand (RANKL) expression in osteoblast/stromal cell at the bone metastatic sites, which leads to inhibition of osteolytic bone destruction caused by NCI-H292 cells. Erlotinib inhibited the proliferation of NCI-H292 cells in in vitro. Erlotinib suppressed the production of osteolytic factors, such as parathyroid hormone-related protein (PTHrP), IL-8, IL-11 and vascular endothelial growth factor (VEGF) in NCI-H292 cells. Furthermore, erlotinib also inhibited osteoblast/stromal cell proliferation in vitro and the development of osteoclasts induced by RANKL in vitro. In conclusion, erlotinib inhibits tumor-induced osteolytic invasion in bone metastasis by suppressing osteoclast activation through inhibiting tumor growth at the bone metastatic sites, osteolytic factor production in tumor cells, osteoblast/stromal cell proliferation and osteoclast differentiation from mouse bone marrow cells

Comparison of Esterman disability scores obtained using Goldmann perimetry and the Humphrey field analyzer in Japanese low-vision patients.

PURPOSE:To compare the Esterman Disability Score (EDS) obtained with Goldmann perimetry (GP) testing and the Humphrey field analyzer (HFA) in low vision Japanese subjects. Subjects were also divided into groups by diagnosis to examine how disease influences EDS measurements. METHODS:The EDS was obtained using GP (GP-EDS) and the built-in testing program of the HFA (HFA-EDS). Tests were performed within 3 months of each other. Regression analyses were used to examine the relationship between GP-EDS and HFA-EDS. RESULTS:A total of 128 visually impaired subjects were included in this study. Subjects had low vision because of glaucoma (57 subjects), age-related macular degeneration (AMD, 17 subjects), retinitis pigmentosa (RP, 17 subjects), and other causes (37 subjects). The GP-EDS obtained was well-correlated with HFA-EDS (r = 0.87, P < 0.001) and it was possible to estimate HFA-EDS from GP-EDS. The GP-EDS was significantly lower than the HFA-EDS in eyes with glaucoma and RP. There was no significant difference between EDS values in eyes with AMD or other disease. CONCLUSION:The GP-EDS correlated well with the HFA-EDS. However, the relationship between the EDS measured with the two different testing modalities varies by disease

The NH2-terminal region of the active domain of sonic hedgehog is necessary for its signal transduction

AbstractThe NH2-terminal domain of sonic hedgehog (residue 25–198) was expressed in both yeast and animal cells. The yeast-derived NH2-terminal domain of sonic hedgehog was less active by far than the animal cell-derived counterpart. The yeast-derived NH2-terminal domain of sonic hedgehog lacked 10 amino acids from the NH2-terminus. This cleavage of the yeast-derived NH2-terminal domain of sonic hedgehog might due to Kex 2. In contrast, a mutant yeast-derived NH2-terminal domain of sonic hedgehog (Lys-33 to Thr) retained its NH2-terminus and its activity was comparable to that of the animal cell-derived NH2-terminal domain of sonic hedgehog. The NH2-terminal deleted NH2-terminal domain of sonic hedgehog completely lost its activity, nevertheless it inhibited the alkaline phosphatase activity induced by the animal cell-derived NH2-terminal domain of sonic hedgehog in a dose-dependent manner. These data suggest that the NH2-terminal deleted NH2-terminal domain of sonic hedgehog retains a receptor-binding ability and that the NH2-terminal peptide of the NH2-terminal domain of sonic hedgehog is necessary for its signal transduction

Biomarkers for antitumor activity of bevacizumab in gastric cancer models

Abstract Background Bevacizumab is a humanized monoclonal antibody to human vascular endothelial cell growth factor (VEGF) and has been used for many types of cancers such as colorectal cancer, non-small cell lung cancer, breast cancer, and glioblastoma. Bevacizumab might be effective against gastric cancer, because VEGF has been reported to be involved in the development of gastric cancer as well as other cancers. On the other hand, there are no established biomarkers to predict the bevacizumab efficacy in spite of clinical needs. Therefore, we tried to identify the predictive markers for efficacy of bevacizumab in gastric cancer patients by using bevacizumab-sensitive and insensitive tumor models. Methods Nine human gastric and two colorectal cancer mouse xenografts were examined for their sensitivity to bevacizumab. We examined expression levels of angiogenic factors by ELISA, bioactivity of VEGF by phosphorylation of VEGFR2 in HUVEC after addition of tumor homogenate, tumor microvessel density by CD31-immunostaining, and polymorphisms of the VEGF gene by HybriProbe™ assay. Results Of the 9 human gastric cancer xenograft models used, GXF97, MKN-45, MKN-28, 4-1ST, SC-08-JCK, and SC-09-JCK were bevacizumab-sensitive, whereas SCH, SC-10-JCK, and NCI-N87 were insensitive. The sensitivity of the gastric cancer model to bevacizumab was not related to histological type or HER2 status. All tumors with high levels of VEGF were bevacizumab-sensitive except for one, SC-10-JCK, which had high levels of VEGF. The reason for the refractoriness was non-bioactivity on the phosphorylation of VEGFR2 and micro-vessel formation of VEGF, but was not explained by the VEGF allele or VEGF165b. We also examined the expression levels of other angiogenic factors in the 11 gastrointestinal tumor tissues. In the refractory models including SC-10-JCK, tumor levels of another angiogenic factor, bFGF, were relatively high. The VEGF/bFGF ratio correlated more closely with sensitivity to bevacizumab than with the VEGF level. Conclusions VEGF levels and VEGF/bFGF ratios in tumors were related to bevacizumab sensitivity of the xenografts tested. Further clinical investigation into useful predictive markers for bevacizumab sensitivity is warranted.</p

The association between photoreceptor layer thickness measured by optical coherence tomography and visual sensitivity in glaucomatous eyes

<div><p>Purpose</p><p>To assess the thickness of the photoreceptor layer in the macular region in glaucomatous eyes.</p><p>Method</p><p>Humphrey 10–2 visual field (VF) testing was carried out and mean threshold (mTH) was calculated in 118 eyes from 118 patients with open angle glaucoma. Macular optical coherence tomography (OCT) measurements (RS 3000, Nidek Co.ltd., Aichi, Japan) were also carried out in all eyes. Thickness measurements were recorded in the outer segment and retinal pigment epithelium (OS+RPE), the nerve fiber layer (NFL), the ganglion cell layer and inner plexiform layer (GCL+IPL), the inner nuclear layer and outer plexiform layer (INL+OPL) and the outer nuclear layer and inner segment (ONL+IS). The relationship between mTH and the thickness of these five different layers was investigated. Additionally, the influence of OS+RPE on mTH was investigated using partial correlation eliminating the effect of other variables of NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length.</p><p>Results</p><p>The thickness of the OS+RPE layer was significantly decreased with the decrease of mTH (coefficient = 0.63 p <0.001). Partial correlation analysis suggested OS+RPE thickness is significantly (coefficient = 0.31, p <0.001) related to mTH, independent from NFL, GCL+IPL, INL+OPL, ONL+IS, age, gender and axial length.</p><p>Conclusions</p><p>The thickness of the RPE+OS layer appears to be related to visual sensitivity in glaucoma.</p></div

The Relationship between Corvis ST Tonometry and Ocular Response Analyzer Measurements in Eyes with Glaucoma

<div><p>It is important to compare the results of Corneal Visualization Scheimpflug Technology instrument (CST) measurements and Reichert Ocular Response Analyzer (ORA) parameters. The purpose of the study was to investigate the association between CST measurements and ORA parameters in ninety-five patients with primary open-angle glaucoma. Measurements of CST, ORA, axial length (AL), average corneal curvature (CC), central corneal thickness (CCT) and intraocular pressure (IOP) with Goldmann applanation tonometry (GAT) were carried out. The association between CST and ORA parameters was assessed using linear regression analysis, with model selection based on the second order bias corrected Akaike Information Criterion index. Measurements from ORA (corneal hysteresis [CH] and corneal response factor [CRF]) had high intraclass correlation coefficients (ICC) and low coefficients of variation, but some CST parameters showed much lower reproducibility, namely: A1 length, A2 length, highest concavity time and peak distance. Of 12 CST parameters tested, 8 were significantly correlated with CH and 10 were significantly correlated with CRF, however, the magnitude of the correlation coefficients were weak to moderate at best. The optimal model to explain CH using CST measurements was given by: CH = -76.3 + 4.6*A1 time + 1.9*A2 time + 3.1 * highest concavity deformation amplitude + 0.016*CCT (R² = 0.67, p <0.001). Similarly, the optimal model for CRF was given by: CRF = -53.5 + 4.2*A1 time + 1.9*A1 length + 20.8*A1 deformation amplitude + 0.8*A2 time + 0.017*CCT (R² = 0.73, p <0.001). ORA parameters show higher reproducibility than CST measurements. Although many CST parameters are significantly related to ORA parameters, the strengths of these relationships are weak to moderate.</p></div