In the last two decades, atopic dermatitis (AD) has been of increasing clinical significance in Japan. Eight-20% of patients with AD developed progressive cataracts (cataract-AD) and lens epithelial cells (LECs) were severely damaged. Lens epithelium-derived growth factor (LEDGF) is a newly isolated survival factor. In the presence of LEDGF, LECs survive well and in the absence of LEDGF, they become highly susceptible to stress. We investigated (1) whether auto-antibody (auto-Ab) to LEDGF is present in sera of AD patients and (2) whether depletion of LEDGF by the auto-Ab kills LECs. In sera from 26 patients with AD using ELISA, we found significantly higher levels of auto-Ab to LEDGF than that in a normal control group. Affinity purified auto-Ab to LEDGF from these sera killed LECs without complement activation. Levels of histamine in the AD group were significantly higher and levels of prostaglandin E2 were significantly lower than in the normal group. However, statistically there are no differences between sera from AD and cataract-AD in levels of Ab to LEDGF, histamine, prostaglandin E2 (PGE2), immunoglobulin E (IgE) and eosinophiles. We speculate that cataract-AD may be induced, in part, by a combination of high levels of serum histamine and eye rubbing which could break the blood-aqueous barrier to allow the entry of Ab to LEDGF into the privileged compartment, thus, reducing LEDGF levels, resulting in damage to LECs, and cataract formation.
BACKGROUND. Testing for human papillomavirus (HPV) is an integral part of equivocal cervical cytology triage. Clinical validation of non‐FDA (Food and Drug Administration)–approved methods is therefore important because of the high volume of such tests and the implications for missed high‐grade lesions if test performance is not optimal. METHODS. A preinitiation study and 17 months of follow‐up data using Hybrid Capture II (HC II) HPV detection with SurePath (SP) sample collection were analyzed. Results of HPV tests on abnormal cytology samples were collected and compared with follow‐up results. HPV‐positive rates were determined in cases of low‐grade squamous intraepithelial lesion (LSIL) and high‐grade squamous intraepithelial lesion (HSIL), and follow‐up rates of cervical intraepithelial neoplasia (CIN) were determined in HPV‐positive and ‐negative cases of atypical squamous cells of unknown significance (ASC‐US). Rates were compared with published data using FDA‐validated methods. RESULTS. The preinitiation study showed the test method to be 100% sensitive for the detection of LSIL (20 cases) and HSIL (8). The ASC‐US follow‐up study (2319 cases with 625 having biopsy results) showed that the rate of CIN III+ in HPV +/− cases was 7.8%/1.4%, and of CIN II+ was 17.5%/4.3%, respectively. The positive predictive values/negative predictive values (PPV/NPVs) (CIN II+) for the test were 17.5%/95.7%, respectively. CONCLUSIONS. Published FDA‐validated HPV testing follow‐up data show that the expected rates of CIN III+ and CIN II+ in the HPV‐negative ASC‐US population are 1.4% and 5%, respectively, with PPV/NPVs (CIN II+) of 20%/99%, respectively. By comparison, the present data using HC II with SP show strong similarity, indicating clinical validity for the use of this method. Cancer (Cancer Cytopathol) 2006; © 2006 American Cancer Society.
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