Effect of ambient solar ultraviolet radiation on incidence of squamous-cell carcinoma of the eye

BACKGROUND: We have investigated the geographic distribution of squamous-cell carcinoma of the eye to assess whether solar ultraviolet light is a risk factor for this disease. METHODS: We used routinely collected population-based cancer incidence data and published measurements of ambient solar ultraviolet light in our analysis. FINDINGS: The incidence of squamous-cell carcinoma of the eye declined by 49% of each 10 degrees increase in latitude (p < 0.0001), falling from more than 12 cases per million per year in Uganda (latitude 0.3(0)) to less than O.2 per million per year in the UK (latitude > 50(0)). Solar ultraviolet radiation decreases with increasing latitude, and the incidence of squamous-cell carcinoma of the eye decreased by 29% per unit reduction in ultraviolet exposure (p < 0.0001). INTERPRETATION: Our results are compatible with the hypothesis that exposure to solar ultraviolet light is an important cause of squamous-cell carcinoma of the eye.     

Ionic interactions and the global conformations of the hammerhead ribozyme

Here we investigate the global conformation of the hammerhead ribozyme. Electrophoretic studies demonstrate that the structure is folded in response to the concentration and type of ions present. Folding based on colinear alignment of arms II and III is suggested, with a variable angle subtended by the remaining helix I. In the probable active conformation, a small angle is subtended between helices I and II. Using uranyl photocleavage, an ion binding site has been detected in the long single-stranded region. The folded conformation could generate a preactivation of the scissile bond to permit in-line attack of the 2'-hydroxyl group, with a bound metal ion playing an integral role in the chemistry.     

Do androgens regulate growth hormone-binding protein in adult man?

To determine whether adult serum GH-binding protein (GHBP) is regulated by androgen, serum GHBP concentrations were compared between 20 normal and 18 hypogonadal men matched for age and body mass index, and the effect of im testosterone treatment (250 mg testosterone enanthate) on GHBP levels in the 18 hypogonadal men was studied. Nine of the hypogonadal subjects had coexistent GH deficiency. Serum GHBP concentration was measured by a ligand immunofunctional assay. The mean serum GHBP level in untreated hypogonadal men was not significantly different from that of normal men (0.98 +/- 0.15 vs. 1.17 +/- 0.16 nmol/L). The mean serum insulin-like growth factor I (IGF-I) level was significantly lower in the hypogonadal men (132 +/- 22 vs. 206 +/- 17 ng/mL; P < 0.01). Basal testosterone (3.7 +/- 0.7 nmol/L) in hypogonadal men increased during treatment to a mean level of 29.1 +/- 2.8 nmol/L, which was not significantly higher than that in normal men (22.6 +/- 1.9 nmol/L). The mean serum GHBP level in hypogonadal men fell significantly during treatment to 0.60 +/- 0.11 nmol/L (P = 0.0003), whereas the serum IGF-I level rose significantly to 151 +/- 26 ng/mL (P < 0.04). The decrease in GHBP level was significant in both the GH-sufficient and GH-deficient subjects (P < 0.02 in both instances), whereas the increase in IGF-I level was significant in the GH-sufficient group (199 +/- 22 to 235 +/- 29 ng/mL; P < 0.04) but not in the GH-deficient group (53 +/- 7 to 55 +/- 5 ng/mL; P > 0.8). Thus, serum GHBP is normal in hypogonadal men but is reduced by testosterone treatment irrespective of endogenous GH-secretory status. It was concluded that the effect of testosterone on GHBP is pharmacological and occurs independent of GH mediation.     

Dietary interventions of human carcinogenesis

The diet is a complex mixture that is associated with approximately 30% of human cancer in the U.S. Extensive laboratory studies indicate that the diet is composed of many mutagens/carcinogens as well as antimutagens/anticarcinogens. Overwhelming evidence from epidemiological studies indicates that a diverse diet that is high in fruits and vegetables and low in certain fats, along with moderate caloric intake and exercise, is most closely associated with reduced cancer risk. Dietary intervention studies using complex food items (fruits, vegetables, and fats) support these epidemiological observations; dietary interventions using single compounds (vitamins, antioxidants, etc.) have generally not. Estimates suggest that appropriate dietary changes could reduce the percentage of deaths due to prostate, colorectal, pancreatic, and breast cancer by >/=50%.     

BCL-6 gene mutations in posttransplantation lymphoproliferative disorders predict response to therapy and clinical outcome

Posttransplantation lymphoproliferative disorders (PT-LPDs) represent a heterogeneous group of Epstein-Barr virus-associated lymphoid proliferations that arise in immunosuppressed transplant recipients. Some of these lesions regress after a reduction in immunosuppressive therapy, whereas some progress despite aggressive therapy. Morphological, immunophenotypic, and immunogenotypic criteria have not been useful in predicting clinical outcome. Although structural alterations in oncogenes and/or tumor suppressor genes identified in some PT-LPDs correlate with a poor clinical outcome, the presence of these alterations has not been a consistently useful predictor of lesion regression after reduction of immunosuppression. We examined 57 PT-LPD lesions obtained from 36 solid organ transplant recipients for the presence of mutations in the BCL-6 proto-oncogene using single-strand conformation polymorphism and sequence analysis, followed by correlation with histopathologic classification and clinical outcome, which was known in 33 patients. BCL-6 gene mutations were identified in 44% of the specimens and in 44% of the patients; none were identified in the cases classified as plasmacytic hyperplasia. However, mutations were present in 43% of the polymorphic lesions and 90% of the PT-LPDs diagnosed as non-Hodgkin's lymphoma or multiple myeloma. BCL-6 gene mutations predicted shorter survival and refractoriness to reduced immunosuppression and/or surgical excision. Our results suggest that the BCL-6 gene structure is a reliable indicator for the division of PT-LPDs into the biological categories of hyperplasia and malignant lymphoma, of which only the former can regress on immune reconstitution. The presence of BCL-6 gene mutations may be a useful clinical marker to determine whether reduction in immunosuppression should be attempted or more aggressive therapy should be instituted.