Parallel induction of ATM-dependent pro- and antiapoptotic signals in response to ionizing radiation in murine lymphoid tissue.

The ATM protein kinase, functionally missing in patients with the human genetic disorder ataxia-telangiectasia, is a master regulator of the cellular network induced by DNA double-strand breaks. The ATM gene is also frequently mutated in sporadic cancers of lymphoid origin. Here, we applied a functional genomics approach that combined gene expression profiling and computational promoter analysis to obtain global dissection of the transcriptional response to ionizing radiation in murine lymphoid tissue. Cluster analysis revealed a prominent pattern characterizing dozens of genes whose response to irradiation was Atm-dependent. Computational analysis identified significant enrichment of the binding site signatures of NF-kappaB and p53 among promoters of these genes, pointing to the major role of these two transcription factors in mediating the Atm-dependent transcriptional response in the irradiated lymphoid tissue. Examination of the response showed that pro- and antiapoptotic signals were simultaneously induced, with the proapoptotic pathway mediated by p53 targets, and the prosurvival pathway by NF-kappaB targets. These findings further elucidate the molecular network induced by IR, point to novel putative NF-kappaB targets, and suggest a mechanistic model for cellular balancing between pro- and antiapoptotic signals induced by IR in lymphoid tissues, which has implications for cancer management. The emerging model suggests that restoring the p53-mediated apoptotic arm while blocking the NF-kappaB-mediated prosurvival arm could effectively increase the radiosensitivity of lymphoid tumors.

Recurrent ocular herpes simplex keratitis following excimer laser photorefractive keratectomy in a rabbit model.

PURPOSE: Reactivation of latent herpes simplex virus (HSV) by excimer laser photorefractive keratectomy(PRK) has been reported previously in the literature. This study evaluates the extent of such HSV reactivation and determines whether corneal de-epithelialization prior to PRK or the laser treatment itself induces this response. METHODS: Twenty three normal 1.5-2.5 kg New Zealand white rabbits were infected on the surface of the cornea with HSV-1, strain RE. The animals were monitored until resolution and then divided into two treatment groups: 1) de-epithelialization alone, and 2) de-epithelialization plus laser. Animals were evaluated in a masked fashion by clinical examination and viral cultures twice a week through day 28. RESULTS: The reactivation rate for group 1 (de-epithelization alone) was 0.0%, and for group 2 (PRK) was 67% by slit lamp biomicroscopy. Viral culture positivity rate matched these findings. CONCLUSIONS: Excimer laser (193 nm) treatment can trigger viral shedding and reactivation of herpetic ocular disease in the latently infected rabbit. De-epithelialization alone is not sufficient to cause such viral reactivation or keratitis. Our findings suggest that patients with a history of herpetic keratitis undergoing PRK are at increased risk of HSV reactivation as a result of exposure to the excimer laser.

Intraoperative PAR corneal topography system (CTS): comparison of its keratometric readings to manual keratometer, auto-keratometer, EyeSys Corneal Analysis system, and slit lamp PAR CTS in healthy eyes.

PURPOSE: To compare the keratometric readings obtained from Intraoperative PAR Corneal Topography System (IOPAR) to those produced by manual keratometer (Mnl-Km), autokeratometer (Auto-Km), EyeSys CAS (EyeSys Corneal Analysis System) and slit lamp PAR CTS in healthy eyes. METHODS: All instruments were calibrated prior to use and only data from the best image obtained was used for statistical analysis. Simulated keratometry readings obtained from the central 3-mm zone of the corneas by IOPAR, including flat (K1) and steep (K2) keratometry readings, average keratometric power (AK), astigmatism (As) (difference between steep and flat keratometry readings) and the axis of the steep meridian (Ax) were compared to those from four other units. The latter units were also compared among themselves. Statistical analysis was done for right and left eyes separately. For each variable, average differences between the measurements taken from pairs of instruments were estimated, with corresponding 95% confidence intervals. The degree of agreement between pairs of instruments on individual measurements was additionally assessed, via the use of "Bland-Altman"-type plots, and estimates of the proportion of cases achieving satisfactory agreement. Additionally, for every variable, the average of the measurements taken from the different instruments were compared. RESULTS: Forty-five (22 right and 23 left) normal corneas of 26 volunteers were examined. On the average, IOPAR tended to measure K1 higher than slit lamp PAR CTS system. Because K2 measurements taken by the IOPAR were higher than that of all other instruments, the As measurements, on the average, were also higher than that of others, with the exception of the PAR CTS. For the same reasons, the IOPAR produced average AK readings that were higher than those taken by EyeSys CAS and PAR CTS. When the individual measurements taken by the IOPAR were compared with each of the other units, according to the arbitrary designation of satisfactory agreement within +/-0.5 D (for K1, K2, AK, and As) and +/-20 degrees (for Ax), for almost all parameters, proportion of differences that were within the agreement range varied from 0.33 to 0.82, with wide confidence intervals (confidence interval lower limits ranging from 0.20 to 0.61 and upper limits ranging from 0.62 to 0.94). CONCLUSIONS: IOPAR is a clinically useful topographic system, producing qualitative and quantitative data in the operating environment that, in normal corneas, on the average, matches those produced by the other units in the clinic. When individually analyzed, its keratometric measurements may show greater variations with respect to other units. Further studies with multiple examiners, in corneas with high or irregular astigmatism are required to establish its reproducibility and efficacy.

Is intraoperative topography predictive of postoperative topographical changes following refractive surgery?

PURPOSE: To evaluate the usefulness of measuring corneal topography intraoperatively by Intraoperative PAR Corneal Topography System (IOPAR CTS) to predict the postoperative topographical changes in patients undergoing refractive surgery. METHODS: Topographical measurements of 9 eyes of 9 patients were taken by IOPAR CTS: 6 immediately after Intrastromal Corneal Ring Segments (ICRS) placement surgery and 3 immediately after Photorefractive Keratectomy (PRK) surgery. The topographical images taken by IOPAR CTS were analyzed to determine the quality of the image produced and the correlation of the keratometric data from the central 3 mm of cornea with measurements taken from an autokeratometer (Auto-Km) and the EyeSys Corneal Analysis System (CAS) for the same eyes taken three months following the procedure. RESULTS: At the 3-month postoperative exam, the correlation coefficients for flat (K1), steep (K2), and average keratometry (AK) readings produced by the Auto-Km and the EyeSys CAS were quite high. However, the correlation coefficients for K1, K2, AK, As or steep meridian axis (Ax) readings taken intraoperatively by IOPAR CTS were quite low when compared to the readings taken by either the Auto-Km or EyeSys CAS three months postoperatively. CONCLUSION: We found IOPAR CTS, relatively difficult to perform in the operating room during refractive surgical procedures and not useful clinically in predicting the postoperative topographical changes induced by ICRS or PRK procedure. Further studies are required to establish the efficacy and reproducibility of the instrument.

Effect on caries experience of lifetime residents after 10 years of fluoridation in Townsville, Australia.

An oral health survey was conducted in the tropical city of Townsville 10 years after its water supply was fluoridated to a level of 0.7 parts/106. The results of the calibration of examiners prior to the survey are presented. Checks on the consistency and comparability of the results obtained by each examiner during the survey show that the results are reliable and reproducible. Dental caries experience of both primary and permanent teeth was found to be significantly lower in Townsville than in 16 non-fluoridated towns. Comparisons are also made between the prevalence of caries in Townsville and four naturally fluoridated towns.