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PubMed2006

Risk factors for histological types and anatomic sites of cutaneous basal-cell carcinoma: an italian case-control study.

Different clinico-pathologic subtypes and anatomic sites of basal-cell carcinoma (BCC) may display distinct characteristics and mechanisms of development. However, scanty information exists on potential differences in etiological factors for BCC according to histotype and anatomic location. Thus, we analyzed data from an Italian case-control study, including 528 subjects with newly diagnosed, histologically confirmed BCC and 512 controls admitted to the same hospitals with acute conditions. The multivariate odds ratio (OR) of nodular (OR=1.53) but not superficial (OR=0.71) BCC was increased for occupational exposure to sunlight. Considering the anatomic site of BCC, the corresponding values were 1.46 for head/neck and 0.74 for truncal location. Direct associations were observed with recreational sunlight exposure, eye color, red hair, and number and early age of severe sunburn episodes, along with some differences in risk between histotypes and anatomic sites. This study confirmed the role of (intermittent) sun exposure and phenotypic characteristics as risk factors for BCC, and suggested etiological differences between nodular and superficial histotypes and between head/neck and truncal locations.

Basal Cell Carcinoma↗

PubMed1998

Role of multiple trans-acting regulators in modifying the effect of the retrotransposon copia on host gene expression in Drosophila.

We have examined the combinatorial effect of five trans-acting modifiers of white apricot, a copia retrotransposon-induced allele of the white eye-color gene. Quantitation of steady-state levels of copia transcripts for various modifier combinations at different developmental stages using northern analysis reveals nonadditivity and epistasis. Interestingly, extensive overexpression of copia transcripts caused by the modifier Ufo is altered up to twofold in level when Ufo is combined with either of the modifiers Mow or Wow. In general, double combinations do not elevate the level of copia transcripts more than twofold. The role of suppressor mutations in modifying the effect of transposable elements on host gene expression is discussed.

Animals↗

PubMed2003

Cis- and trans-acting influences on telomeric position effect in Drosophila melanogaster detected with a subterminal transgene.

One model of telomeric position effect (TPE) in Drosophila melanogaster proposes that reporter genes in the vicinity of telomeres are repressed by subterminal telomere-associated sequences (TAS) and that variegation of these genes is the result of competition between the repressive effects of TAS and the stimulating effects of promoters in the terminal HeT-A transposon array. The data presented here support this model, but also suggest that TPE is more complex. Activity of a telomeric white reporter gene increases in response to deletion of some or all of the TAS on the homolog. Only transgenes next to fairly long HeT-A arrays respond to this trans-interaction. HeT-A arrays of 6-18 kb respond by increasing the number of dark spots on the eye, while longer arrays increase the background eye color or increase the number of spots sufficiently to cause them to merge. Thus, expression of a subtelomeric reporter gene is influenced by the telomere structure in cis and trans. We propose that the forces involved in telomere length regulation in Drosophila are the underlying forces that manifest themselves as TPE. In the wild-type telomere TAS may play an important role in controlling telomere elongation by repressing HeT-A promoter activity. Modulation of this repression by the homolog may thus regulate telomere elongation.

Animals↗

PubMed1984

Noise-induced hearing loss as influenced by other agents and by some physical characteristics of the individual.

The interaction of noise with a variety of other agents and with some physical characteristics of the individual to produce noise-induced hearing loss is reviewed critically. The review is restricted, for the most part, to publications since 1970. Other agents interacting with steady-state noise that are reviewed here include: (1) ototoxic drugs (kanamycin, neomycin, ethacrynic acid, furosemide, and salicylates), (2) impulse noise, and (3) whole-body vibration. Physical characteristics of the individual that are reviewed are: (1) age, (2) presence of previous hearing loss from prior noise exposure, (3) eye color, and (4) race. Suggestions for future research in this general area are also made. Some of these suggestions are as follows: (1) to extend studies of the interaction of steady-state noise with impulse noise, salicylates, and whole-body vibration to encompass a broader range of exposure conditions, including exposure conditions typically encountered by the worker, (2) to develop an animal model of presbycusis to explore the interactions of noise-induced hearing loss and presbycusis, and (3) to explore the potential interactions resulting from concurrent exposure to multiple agents, such as impulse noise and ototoxic drugs, in younger, more susceptible animals.

Acoustic Stimulation↗

PubMed1988

Health effects of sunlight exposure in the United States. Results from the first National Health and Nutrition Examination Survey, 1971-1974.

The dermatologic component of the first National Health and Nutrition Examination Survey (N = 20,637), conducted from 1971 through 1974, documented the deleterious effect of ultraviolet radiation on selected skin and eye conditions. Actinic skin damage was more frequent in white men with high as compared with low sunlight exposure, 36.7% vs 23.3%, respectively. Among white women, the corresponding figures were 34.1% vs 18.6%, respectively. Actinic damage was found more often in individuals with light eye color. Basal cell epitheliomas were found in 11.3% of white men aged 65 to 74 years who had severely actinic-damaged skin as compared with 1.0% of those with undamaged skin. Sunlight exposure was positively associated with localized hypomelanism, localized hypermelanism, seborrheic keratoses, senile lentigines, freckles, acne rosacea, spider nevi, varicose veins, venus star, dry skin, wrinkled skin, pterygia, arcus senilis, and a variety of minor oral lesions of the tongue, palate, and buccal mucosa. These findings suggest that a large number of dermatologic conditions, which may in part result from overexposure to sunlight, may be preventable.

Adolescent↗

PubMed1996

Perturbation of nuclear architecture by long-distance chromosome interactions.

SUMMARY: Position-effect variegation (PEV) describes the stochastic transcriptional silencing of a gene positioned adjacent to heterochromatin. Using FISH, we have tested whether variegated expression of the eye-color gene brown in Drosophila is influenced by its nuclear localization. In embryonic nuclei, a heterochromatic insertion at the brown locus is always spatially isolated from other heterochromatin. However, during larval development this insertion physically associates with other heterochromatic regions on the same chromosome in a stochastic manner. These observations indicate that the brown gene is silenced by specific contact with centromeric heterochromatin. Moreover, they provide direct evidence for long-range chromosome interactions and their impact on three-dimensional nuclear architecture, while providing a cohesive explanation for the phenomenon of PEV.

Animals↗

PubMed1996

Latanoprost, a prostaglandin analog, for glaucoma therapy. Efficacy and safety after 1 year of treatment in 198 patients. Latanoprost Study Groups.

PURPOSE: To determine efficacy and safety of latanoprost, a prostaglandin analog for glaucoma, during 1 year of treatment. METHODS: After baseline measurements, 0.005% latanoprost was topically applied once daily for 12 months in patients from Scandinavia, the United Kingdom, and the United States who had elevated intraocular pressure (IOP). Diagnoses included ocular hypertension, chronic open-angle glaucoma, exfoliation syndrome, and pigment dispersion syndrome. Treatment was masked for the first 6 months and open-label during the second 6 months. RESULTS: Of the 272 patients initially enrolled, withdrawals were due to inadequate IOP control (1%), increased iris pigmentation (5%), other ocular problems (3%), systemic medical problems (3%), and nonmedical reasons (14%). Latanoprost significantly (P < 0.0001) reduced diumal IOP from 25.3 +/- 3.0 mmHg (mean +/- standard deviation) at baseline to 17.4 +/- 2.7 mmHg (32% reduction) at 12 months in the 198 patients who completed 1 year of treatment. The IOP reduction was maintained at a consistent level throughout the 12 months without evidence of drift, and was not affected by sex, age, race, or eye color. Overall, latanoprost caused a possible or definite increase in iris pigmentation in 12% of the 272 patients, all of whom had multicolored irides at baseline. One half of these patients with increased pigmentation withdrew before completing 1 year of therapy. Visual field, optic disc cupping, visual acuity, refractive error, conjunctival hyperemia, aqueous flare, anterior chamber cellular response, lens examination, blood pressure, heart rate, blood tests, and urinalysis were not appreciably altered. CONCLUSION: Latanoprost safely and effectively reduces IOP for 1 year in patients of diverse nationalities, providing further evidence for its usefulness in chronic glaucoma therapy.

Administration, Topical↗

PubMed1993

Individual susceptibility to noise-induced hearing loss: an old topic revisited.

The wide range in susceptibility to noise-induced hearing loss has intrigued researchers and hearing conservationists alike. Some of these differences in variability have been attributed to various intrinsic factors such as eye color, gender, age, etc. However, a review of controlled research shows that the influence of these intrinsic variables is relatively small and cannot explain the wide range of hearing loss observed in demographic studies. Furthermore, uncontrolled variables or unrecognized drug and noise interaction may obscure the relation between noise exposure and hearing loss. With the growing understanding of the physiology of the auditory system, new possibilities are emerging that may explain the range of susceptibility. A review of the role of acoustic reflex effectiveness, cochlear efferent function, and history of noise exposure provide a perspective for future strategies in predicting susceptibility to noise-induced hearing loss.

Age Factors↗

PubMed2002

Fluorescent transformation markers for insect transgenesis.

The first effectively achieved germ-line transformations of non-drosophilid insects were based on mutant rescue of eye color phenotypes. However, for most insect species neither visible mutants nor corresponding cloned genes are available. Therefore, the development of broadly applicable and reliable transformation markers will be of great importance to fully exploit the enormous potential transgenic insect technology has to offer. Here we review transposon-mediated germ-line transformation approaches that employ green fluorescent protein (GFP) variants to identify successful gene transfer. Furthermore, we provide novel data on the use of DsRed as an additional red fluorescent transformation marker for insect transgenesis. In conclusion, fluorescent proteins controlled by suitable strong promoters possess ideal characteristics to serve as transformation markers for a wide range of insect species.

Animals↗

PubMed1994

The Lighten up (Lip) gene of Drosophila melanogaster, a modifier of retroelement expression, position effect variegation and white locus insertion alleles.

We are interested in identifying single gene mutations that are involved in trans-acting dosage regulation in order to understand further the role of such genes in aneuploid syndromes, various types of dosage compensation as well as in regulatory mechanisms. The Lighten up (Lip) gene in Drosophila melanogaster was identified in a mutagenic screen to detect dominant second site modifiers of white-blood (wbl), a retrotransposon induced allele of the white eye color locus. Lip specifically enhances the phenotype of wbl as well as a subset of other retroelement insertion alleles of white, including the copia-induced allele, white-apricot (wa), and six alleles caused by insertion of I elements. We isolated six alleles of Lip which are all recessive lethal, although phenotypically additive heteroallelic escapers were recovered in some combinations. Lip also suppresses position effect variegation, indicating that it may have a role in chromatin configuration. Additionally, Lip modifies the total transcript abundance of both the blood and copia retrotransposons, having an inverse effect on the steady state level of blood transcripts, while showing a non-additive effect on copia RNA.

Alleles↗

PubMed1998

Regena (Rga), a Drosophila homolog of the global negative transcriptional regulator CDC36 (NOT2) from yeast, modifies gene expression and suppresses position effect variegation.

A mutation in Regena (Rga) was isolated in screens for modifiers of white eye color gene expression. The reduction in the level of the Rga product results in a complex modulation of white mRNA both positively and negatively, depending on the developmental stage. In addition to white, Rga also affects the expression of several other tested genes, with one of them, Vinculin, being regulated in a strong sex-specific manner. Rga was cloned by transposon tagging. Its predicted product lacks any recognized nucleic acid-binding motif but is homologous to a global negative transcriptional regulator, CDC36 (NOT2), from yeast. Rga also acts as a suppressor of position effect variegation, suggesting that a possible function of Rga could be mediation of an interaction between chromatin proteins and the transcriptional complex.

Amino Acid Sequence↗

PubMed2006

Color fingerprinting of proteins by calixarenes embedded in lipid/polydiacetylene vesicles.

"Naked eye" color detection of proteins was achieved by embedding calixarene receptors within vesicles comprising phospholipids and the chromatic polymer polydiacetylene. Dramatic visible absorbance changes were induced through electrostatic interactions between the protein surface and the vesicle-incorporated hosts. The colorimetric responses could be induced by micromolar protein concentrations, and furthermore, specific protein fingerprints could be obtained by incorporating different receptors within the vesicles. Fluorescence and circular dichroism experiments confirmed the relationship between the colorimetric phenomena and protein docking on the surface of the chromatic vesicles. The colorimetric assay constitutes a generic platform for high-sensitivity detection of soluble proteins and for evaluation of protein surface charge distribution.

Calixarenes↗

PubMed1999

Tobacco smoking contributes little to facial wrinkling.

BACKGROUND: The potential detrimental effects of tobacco smoking have been widely cited. Tobacco smoking has been linked with facial wrinkling, but some previous studies have failed to take into account a number of potential confounders or were unblinded and thus subjective to bias. OBJECTIVE: This study was designed to determine if there was increased facial wrinkling in smokers directly associated with tobacco usage after controlling for solar risk behavior. SUBJECTS: Eighty-two smokers (> 10 cigarettes per day) and 118 non-smokers (< 100 lifetime cigarettes) were recruited. Caucasian participants completed a questionnaire designed to assess demographic variables and other suspected factors related to wrinkling. METHODS: Three dermatologists, blinded to demographic information, reviewed three photographs of each subject and rated the wrinkling on a 100 mm visual analog scale. Stepwise linear regression was performed on all variables which attained a P < 0.1 level of independent significance. RESULTS: Overall the model accounted for 75.4% (P = 0.0001) of the variance in wrinkling, and predictive variables (P < or = 0.02) included age (partial R2 = 0.69), smoking pack years (R2 = 0.04), hours of outdoor work (R2 = 0.008), freckling (R2 = 0.007), and eye color (R2 = 0.004). A second model was created excluding age which accounted for 37.8% of the variance. The predictive variables in the second model (P < 0.08) included education (partial R2 = 0.08), smoking pack years (R2 = 0.05), hours of outdoor work (R2 = 0.03), weight change (R2 = 0.02), female sex (R2 = 0.02), hours of lifetime sun (R2 = 0.03), tanning bed use (R2 = 0.01), and sunscreen use (R2 = 0.02). CONCLUSIONS: Smoking may significantly contribute to facial wrinkling, but accounts for only 6% of the explained variance. If there is a role for tobacco smoking in causing wrinkling, this role is a minor one.

Adult↗

PubMed1992

Variation and covariates of the number of benign nevi in adolescents.

Melanocytic nevi of diameter greater than or equal to 2 mm were counted on most of the skin surface of 349 adolescents aged 14-15 years of European race or ethnicity in Dunedin, New Zealand. Total counts are described by means of a form of Poisson-error log-linear modeling suitable for data showing unexplained variation (NE Breslow, Appl Statist 1984;33:38-44). There were marked interpersonal variation in the number of nevi; only some was attributable to observed factors. The mean and median counts were 23.8 and 18 nevi, respectively. The estimated ratio of the number of nevi for females compared with males was 0.7 (95% confidence interval (CI) 0.6-0.8). Greater amounts of sunbathing were associated with greater numbers of nevi. Hair and eye color, socioeconomic status, and sunburn history did not show statistically significant effects. Time since menarche and shaving status also showed no effects. Lack of suntan was associated with lower counts. Freckling was positively correlated with higher counts; the severe freckling group had an estimated ratio of 1.9 (95% CI 1.3-2.8) compared with those with no or very few freckles. The results are consistent with the hypothesis that ultraviolet radiation exposure from recreational sun exposure positively influences the total burden of nevi in normal subjects. Comparison with other epidemiologic studies suggests that the typical ultraviolet radiation dose-nevus yield curve might be steeper in males than females. Unexplained variation of nevus count may reflect heterogeneity of constitutional factors not yet measured in epidemiologic studies.

Adolescent↗

PubMed1978

Xanthommatin biosynthesis in wild-type and mutant strains of the Australian sheep blowfly Lucilia cuprina.

The synthesis of eye pigments has been studied in the seven eye color mutants of the Australian sheep blowfly, Lucilia cuprina. Six appears to be affected primarily in the synthesis of xanthommatin. In wild type, the onset of xanthommatin biosynthesis occurs midway through metamorphosis. Developmental patterns of accumulation of the xanthommatin precursors tryptophan, kynurenine, and 3-hydroxykynurenine have also been established for wild type. By determining the levels of these precursors in late pupae of the mutants, it has been shown that the mutant yellowish accumulates excess tryptophan and the mutant yellow accumulates excess kynurenine. The implications of these results--that yellowish lacks tryptophan oxygenase, thus failing to convert tryptophan to kynurenine, and that yellow lacks kynurenine hydroxylase (blockade in the conversion of kynurenine to 3-hydroxykynurenine)--have been confirmed. This has involved in vitro assays of tryphophan oxygenase and precursor feeding experiments. The precursor accumulation patterns are less clear for the other mutants.

Amino Acids↗

PubMed2001

Molecular nature of 11 spontaneous de novo mutations in Drosophila melanogaster.

To investigate the molecular nature and rate of spontaneous mutation in Drosophila melanogaster, we screened 887,000 individuals for de novo recessive loss-of-function mutations at eight loci that affect eye color. In total, 28 mutants were found in 16 independent events (13 singletons and three clusters). The molecular nature of the 13 events was analyzed. Coding exons of the locus were affected by insertions or deletions >100 nucleotides long (6 events), short frameshift insertions or deletions (4 events), and replacement nucleotide substitutions (1 event). In the case of 2 mutant alleles, coding regions were not affected. Because approximately 70% of spontaneous de novo loss-of-function mutations in Homo sapiens are due to nucleotide substitutions within coding regions, insertions and deletions appear to play a much larger role in spontaneous mutation in D. melanogaster than in H. sapiens. If so, the per nucleotide mutation rate in D. melanogaster may be lower than in H. sapiens, even if their per locus mutation rates are similar.

Alleles↗

PubMed1993

Mutations at the Darkener of apricot locus modulate transcript levels of copia and copia-induced mutations in Drosophila melanogaster.

Mutations of the Doa locus of Drosophila melanogaster darken the eye color of the copia-induced white(apricot) (wa) allele and increase the accumulation of white promoter-initiated transcripts encoding functional mRNA. We show here that quantities of transcripts initiated in both long terminal repeats (LTRs) of the specific wa-copia element are increased, and those initiating in the 5' LTR of the element are structurally altered, yielding a slightly shortened transcript. Accumulation of host-initiated transcripts of a copia-induced mutation within the achaete-scute complex, Hairy-wing Ua (HwUa), are reduced by Doa mutations. Finally, we show that homozygosity for Doa mutations increases the accumulation of copia transcripts from the population of elements in the genome. These results suggest that Doa modulates the severity of copia-induced mutations while functioning as a dosage-sensitive modulator of copia transcription.

Alleles↗

PubMed1985

An inquiry into the epidemiology of melanoma.

The authors conducted a study of 404 melanoma patients and 521 control patients of both sexes at Roswell Park Memorial Institute. As have previous investigators, they found that higher risk attaches to upper socioeconomic status, as measured by occupation and education, lightness of complexion and hair, and amount of blue in the admixture of eye color. The authors also found a higher risk among individuals who reacted to sun exposure by burning, blistering, or freckling rather than by tanning. A particular concern was to measure risk associated with exposure to the sun. As have two other investigators, they found that risk decreased with increasing exposure, suggesting either that individuals continually exposed to the sun have less risk because of tanning, or that susceptibles purposely avoid sun exposure, or both. The fact that melanoma occurs with greater frequency on sites exposed to the sun suggests that sun exposure plays a part. These studies showed a dose-response increase in risk (odds ratios of up to 4 for males and over 6 for females) with increases in number of traits possessed, such as light complexion, and burning or freckling in response to sun exposure. This is consistent with the authors' earlier finding of a strong familial aggregation of melanoma.

Adult↗