Molecular cloning of the human gene SUVCC1 associated with the repair of nondimer DNA damage induced by solar UV radiation.

A mutant cell line, DRP 287, sensitive to solar UV radiation and deficient in the repair of solar UV-induced nondimer DNA damage, was derived from ICR 2A frog cells. These cells were transfected with human DNA and a secondary transformant obtained in which normal solar UV sensitivity was restored and the repair defect corrected. The DNA from this secondary transformant was used to construct a genomic DNA library from which a recombinant phage was isolated containing the human gene capable of restoring normal solar UV sensitivity and correcting the repair defect in the DRP 287 cells. This represents the first human gene which has been isolated that is specifically involved in the repair of nondimer DNA damage induced by solar UV radiation. It has been designated SUVCC1 to denote solar UV cross-complementing gene number 1.

Survival, excision repair and inhibition of DNA synthesis in normal human skin fibroblasts exposed to simulated sunlight.

The responses of normal human skin fibroblasts exposed to simulated sunlight produced by a solar simulator were examined. The parameters investigated were cellular survival, excision repair and the inhibition and recovery of DNA synthesis. The latter two effects were examined using the bromodeoxyuridine photolysis assay and the alkaline step elution assay respectively. The results of these experiments are consistent with the conclusion that the lesions induced by simulated sunlight represent a mixture of damage which elicits cellular responses and repair mechanisms similar to those manifested by cells irradiated with UVC and UVA radiation.

Repair of DNA damage induced in systemic lupus erythematosus skin fibroblasts by simulated sunlight.

Skin fibroblasts derived from three normal individuals and three patients exhibiting the disease systemic lupus erythematosus (SLE) were exposed to the simulated sunlight produced by a solar simulator. The induction and repair of DNA damage induced by this treatment were examined. The total number of lesions repaired by excision, as well as the removal of pyrimidine dimers and E. coli endonuclease III--sensitive sites did not differ significantly in the three SLE cell strains compared with normal cells. However, abnormalities in the formation and maintenance of DNA-protein crosslinks (DPC) and DNA single-strand breaks (SSB) were found in SLE-4 and SLE-5 following simulated sunlight exposure. In contrast, SLE-3 cells exhibited responses similar to normal cells in reference to SSB and DPC formation. These findings correlate well with the previously determined UV sensitivity of these SLE cell strains.

Long-term stability and visual outcome after favorable initial response of proliferative diabetic retinopathy to panretinal photocoagulation.

The authors assessed the relationship between early objective response to panretinal photocoagulation (PRP) and the subsequent long-term visual outcome in 59 eyes of 59 consecutive patients who developed proliferative diabetic retinopathy while under the care of a retinal specialist. Thirty five eyes (59%) had regression of high-risk retinopathy characteristics within 3 months of treatment. Eighteen of these eyes (52%) had a final visual acuity of 20/20 or better with a mean follow-up of more than 4 years. Only 2 of the 24 nonresponder eyes (8%) had visual acuity of 20/20 or better. Thirteen of the responder eyes (37%) sustained a delayed vitreous hemorrhage, which was usually self-limited. Three responders underwent vitrectomy with excellent visual results. The authors conclude that the beneficial effect of PRP on visual outcome is directly related to the regression of retinopathy risk factors and that the long-term visual prognosis in high-risk eyes manifesting a favorable initial response to PRP is excellent.

Foveal avascular zone diameter and sickle cell disease.

Patients with sickle cell disease can have a distinct retinopathy in which the posterior pole shows abnormalities, including perifoveolar vascular abnormalities. The foveal avascular zone (FAZ) was examined using fluorescein angiography in patients with sickle cell disease and in healthy normal controls. The longest FAZ diameters of 38 patients (51 eyes) with sickle cell disease were compared with those of the 48 patients (60 eyes) in the control group. The average of the longest FAZ diameter in the patients with sickle cell disease was 1.00 mm compared with 0.61 mm for the controls. This difference was statistically significant (P less than .00001). Within the sickle cell group, there were no significant differences in the FAZ diameters with respect to degree of retinopathy, type of sickle hemoglobinopathy, or visual acuity. Thus, an enlarged FAZ diameter in patients with sickle cell disease is confirmed.

Retrobulbar bupivacaine irrigation for postoperative pain after scleral buckling surgery. A prospective study.

The authors conducted a prospective, randomized, double-masked clinical trial to determine if retrobulbar irrigation with bupivacaine hydrochloride 0.75% (Marcaine) has an effect on postoperative pain after scleral buckling surgery. Fifty consecutive patients undergoing scleral buckling under general anesthesia were randomized to receive either bupivacaine or balanced salt solution as a retrobulbar irrigation at the end of their retinal detachment procedure. Of the 25 patients who received bupivacaine, only three (12%) required parenteral pain relief in the first 24 hours after surgery. This was statistically significant when compared with the 18 (72%) of 25 patients requiring parenteral pain relief in the placebo group (P less than 0.0001). In addition, when questioned about their perception of the degree of postoperative pain, patients in the control group rated their level of pain as significantly more severe than did patients in the bupivacaine group. The authors conclude that retrobulbar irrigation with bupivacaine is a safe and effective way to achieve postoperative pain relief after surgery for scleral buckling.

Effect of optical defocus on the steady state pattern reversal visual-evoked response.

The effects of optical defocusing with convex lenses on the amplitudes of pattern reversal visual-evoked response (PVER) were investigated. With the large check size and high-contrast pattern, PVER amplitudes showed a linear decrease in response to initial defocusing up to +5 to +6 dptr. As the degree of defocus increased, the PVER amplitude, though irregular, continued to show reliable, definite responses up to +25 dptr. With the intermediate check size and pattern contrast, PVER amplitudes displayed a linear decrease, but unlike the large-check/high-contrast condition, diminished to noise level after a defocus of greater than +4 to +5 dptr. From these results, we speculate that two phases in this function curve derive from the large-check/high-contrast condition: first, the contrast- or contour-dependent phase, and, second, the luminosity/movement-dependent phase.

DNA-protein crosslinking in normal and solar UV-sensitive ICR 2A frog cell lines exposed to solar UV-radiation.

DNA-protein crosslinks (DPC) were measured following exposure to the solar UV wavelengths produced by a fluorescent sunlamp in ICR 2A frog cells and two solar UV-sensitive mutants derived from this cell line. Approx. 5-7 DPC per 10(10) dalton were induced in these cells by either 150 kJ/m2 of sunlamp UV greater than 315 nm plus photoreactivating light (PRL) or 10 kJ/m2 of sunlamp UV greater than 295 nm. The irradiated cells were then incubated for 0-24 h and the level of DPC measured using alkaline elution. It was found for the ICR 2A cells exposed to sunlamp UV greater than 315 nm that the level of DPC increased about 3-fold during a 2-h postirradiation incubation and then decreased. The mutant cell lines also showed an enhancement in the level of DPC following irradiation, although it was much less pronounced and the levels decreased much more rapidly. In a similar fashion, the level of DPC increased in ICR 2A cells exposed to sunlamp UV greater than 295 nm with more than a 5-fold enhancement after a 4-h incubation. Once again, the mutant cell lines showed an increase in the level of DPC that was smaller and more transient than the effect in the ICR 2A cells. These results suggests that this enhancement in DPC may be indicative of a process that plays a role in cellular survival following solar UV-irradiation.

Resection of the liver for colorectal carcinoma metastases. A multi-institutional study of long-term survivors.

In this review of a collected series of patients undergoing hepatic resection for colorectal metastases, 100 patients were found to have survived greater than five years from the time of resection. Of these 100 long-term survivors, 71 remain disease-free through the last follow-up, 19 recurred prior to five years, and ten recurred after five years. Patient characteristics that may have contributed to survival were examined. Procedures performed included five trisegmentectomies, 32 lobectomies, 16 left lateral segmentectomies, and 45 wedge resections. The margin of resection was recorded in 27 patients, one of whom had a positive margin, nine of whom had a less than or equal to 1-cm margin, and 17 of whom had a greater than 1-cm margin. Eighty-one patients had a solitary metastasis to the liver, 11 patients had two metastases, one patient had three metastases, and four patients had four metastases. Thirty patients had Stage C primary carcinoma, 40 had Stage B primary carcinoma, and one had Stage A primary carcinoma. The disease-free interval from the time of colon resection to the time of liver resection was less than one year in 65 patients, and greater than one year in 34 patients. Three patients had bilobar metastases. Four of the patients had extrahepatic disease resected simultaneously with the liver resection. Though several contraindications to hepatic resection have been proposed in the past, five-year survival has been found in patients with extrahepatic disease resected simultaneously, patients with bilobar metastases, patients with multiple metastases, and patients with positive margins. Five-year disease-free survivors are also present in each of these subsets. It is concluded that five-year survival is possible in the presence of reported contraindications to resection, and therefore that the decision to resect the liver must be individualized.

Induction of sister-chromatid exchanges in ICR 2A frog cells exposed to 265-313 nm monochromatic ultraviolet wavelengths and photoreactivating light.

Exposure of ICR 2A frog cells to 265 nm, 289 nm, 302 nm or 313 nm monochromatic ultraviolet (UV) wavelengths induced the formation of sister-chromatid exchanges (SCEs). However, treatment of cells with photoreactivating light (PRL) following the UV irradiations resulted in a lower level of SCEs compared with cells incubated in the dark. Hence, it can be concluded that pyrimidine dimers are the principal photoproducts responsible for the induction of SCEs in cells exposed to 265-313 nm UV due to the specificity of DNA photolyase for the light-dependent monomerization of dimers in DNA. It was also found that the maximum yield of induced SCEs in 313 nm-irradiated cells was only about 7 SCEs per cell whereas the plateau values for the shorter wavelengths were approximately 15-20 SCEs per cell. In addition, treatment of cells with 313 nm plus 265 nm light resulted in a lower level of SCEs than in cells exposed to 265 nm UV alone. These results can be interpreted in the context of a replication model for SCE, in which the high level of non-dimer damages produced in the DNA of 313 nm-irradiated cells inhibits the induction of SCEs by the pyrimidine dimers that are also produced by this wavelength.