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PubMed1987

Clinical method for measuring adaptation of tonic accommodation and vergence accommodation.

Previous work indicates that tonic adapters of accommodation and vergence have indirect effects on accommodative vergence and vergence accommodation and that these crosslink responses interact with one another to produce clear and single vision. Clinical measurements of tonic accommodation, tonic vergence, vergence accommodation (CA/C ratio), and accommodative vergence (AC/A ratio) are therefore of value in determining possible binocular vision abnormalities. Currently, clinical methods are only available for measuring the tonic vergence (phoria) and the AC/A ratio. We have determined a fast and accurate method for evaluating both tonic accommodation (accommodative phoria) and vergence accommodation (CA/C ratio). In both procedures, the loop of accommodation was opened with a 0.2 cpd difference of Gaussian (DOG) target. This target was found to be incapable of stimulating any reflex accommodation, yet it is localized in space and can easily stimulate binocular fixation. Our results indicate that opening the loop of accommodation with a pinhole Maxwellian view or with a 0.2 cpd DOG produces similar response values for tonic accommodative aftereffects and vergence accommodation responses. The decay rate of tonic accommodative aftereffects as well as changes in the resting focus of accommodation caused by vergence accommodation (CA/C) can be measured clinically using dynamic retinoscopy in combination with the DOG target. Clinical values of the CA/C ratio obtained with these techniques were highly correlated (r = 0.92) with laboratory measures obtained with an objective infrared optometer and eye trac monitor.

Accommodation, Ocular↗
PubMed1991

Color-mediated contrast sensitivity in disabled readers.

Specific deficits in the processing of transient visual stimuli have been identified in reading-disabled children. It has been suggested that suitably chosen colored filters can assist reading-disabled children but this is controversial. In order to assess how colored lenses might assist a reading-disabled child, we compared contrast sensitivity judgments of 20 disabled readers with those made by 20 good readers of the same age. Contrast sensitivity thresholds were measured over a spatial frequency range of 0.4 to 12.8 cpd. Contrast sensitivity functions were recorded for each child under four different conditions. For each condition the child wore a spectacle frame with a colored filter which had been selected on the basis of the child's best and worst performances on a spatial location task (BEST and WORST), a neutral density optical filter (GRAY), and an untinted filter (CLEAR). The results showed that the best colored filter selected for each of the disabled readers dramatically reduced sensitivity as the spatial frequency moved into the range of printed material (i.e., sensitivity declined sharply from 0.4 to 12.8 cpd). In contrast, there was very little change in sensitivity for the good readers using their best filters. These provocative findings suggest that colored optical filters might improve transient-on-sustained inhibition in disabled readers. It is possible that individually designed filters will provide a way of mitigating the effects of weak transient processing in reading-disabled children. However, our results should not be interpreted as supporting the efficacy of prescribed, colored optical filters as a remediation technique for reading disability.

Child↗
PubMed1995

Small amounts of chromatic aberration influence dynamic accommodation.

The prevailing view of accommodation is that the eye changes focus to maximize luminance contrast by trial and error. Negative feedback is considered essential in this view because luminance contrast provides no directional information. Fincham proposed an alternate view in which longitudinal (axial) chromatic aberration (LCA) provides a directional stimulus for accommodation. For spatial frequencies above approximately 0.5 cpd contrast of the retinal image is different for long, middle, and short spectral waveband components of the image. We varied the amount of LCA in small steps (0.25 D) to determine how much LCA is needed to enhance or impair the response. An infrared optometer monitored accommodation continuously while subjects viewed a yellow/black square-wave grating (3.5 cpd) in a Badal stimulus system. The yellow/black grating was produced by superimposing red (600 nm) and green (520 nm) gratings, and LCA was increased, decreased, neutralized, and reversed by repositioning the red grating component along the axis of the optical system. Target vergence was modulated sinusoidally (0.2 Hz) over a 1 D range (1.5 to 2.5 D) and gain and phase-lag of the accommodation response were determined by Fourier analysis. Subjects accommodated well as long as a normal amount of LCA was present--0.5 D in the correct direction enhanced accommodative gain, and 0.25 D in the reverse direction markedly inhibited the response. We conclude that the contrast of the retinal image in different spectral wavebands specifies focus of the eye, and provides a powerful directional stimulus for reflex accommodation.

Accommodation, Ocular↗
PubMed2002

Effect of dichoptic adaptation on frequency-doubling perimetry.

BACKGROUND: In frequency-doubling technology (FDT) perimetry, the second eye tested has reduced sensitivity. We investigated the cause of this sensitivity reduction. METHODS: Contrast sensitivity was measured for frequency doubling (0.25 cpd, 25 Hz) and nonflickering (4 cpd) gratings, arranged similarly to the targets in the FDT perimeter (Welch Allyn, Skaneateles Falls, NY, and Humphrey Instruments, San Leandro, CA). Various test orders were examined. RESULTS: Frequency-doubling (FD) sensitivity was reduced (0.15 log) in the second eye. A similar reduction occurred when first and second eye gratings were oriented orthogonally, suggesting that dichoptic contrast adaptation was not the cause. FD sensitivity was little affected after testing with nonflickering gratings, suggesting that fatigue effects were small. Sensitivity was reduced when testing was performed after 5 min of opaque occlusion. The use of a translucent occluder eliminated the reduction in sensitivity in the second eye. CONCLUSION: We confirm the presence of reduced sensitivity in the second eye tested with FD perimetry and find that it is caused by delayed light adaptation post-occlusion.

Adaptation, Ocular↗
PubMed2006

Electronic momentary assessment in chronic pain I: psychological pain responses as predictors of pain intensity.

OBJECTIVES AND METHODS: Electronic momentary assessment was employed to substantiate the relevance of psychological functioning in chronic pain. More than 7,100 electronic diaries from 80 patients with varying IASP classified types of chronic pain served to investigate to what extent fear-avoidance, cognitive and spousal solicitous and punishing pain responses explained fluctuations in pain intensity and whether patients with pre-chronic, recently chronic and persistently chronic pain differed in this regard. RESULTS: Psychological pain responses explained 40% of the total variance in pain intensity: almost 24% concerned pain variance that occurred between the CPD patients and 16% pertained to pain variance due to momentary differences within these patients. Separately tested fear-avoidance and cognitive responses each explained about 28% of the total pain variance, while spousal responses explained 9%. Catastrophizing emerged as the strongest pain predictor, followed by pain-related fear and bodily vigilance. Results did not differ with the duration of chronicity. DISCUSSION: Exaggerated negative interpretations of pain, and fear that movement will induce or increase pain strongly predicted CPD pain intensity. Spousal responses-assessed only when the spouse was with the patient who at that moment was in actual pain-may more strongly affect immobility due to pain than pain intensity per se (see part II of the study). The findings substantiate the importance of catastrophizing, fear and vigilance identified primarily in low back pain and extend this to other forms of chronic pain. The compelling evidence of momentary within-patients differences underscores that these must be accounted for in chronic pain research and practice.

Activities of Daily Living↗
PubMed2006

China's syphilis epidemic: a systematic review of seroprevalence studies.

OBJECTIVE: The objective of this study was to investigate syphilis prevalence among low- and high-risk groups in China. GOAL: The goal of this study was to explore the magnitude of China's syphilis epidemic. STUDY DESIGN: A systematic literature review of syphilis seroprevalence studies in China was performed searching PubMed and the Chinese Periodicals Database (CPD). RESULTS: Five and 169 studies were retrieved from PubMed and the CPD, respectively. From 2000 to 2005, select low-risk groups had the following median syphilis prevalence: antenatal women (0.45%), premarital individuals (0.66%), and food and service employees (0.3%). Select high-risk groups had the following median prevalence: incarcerated female sex workers (12.49%), drug users (6.81%), and men who have sex with men (14.56%). In the last decade, prevalence has increased in all groups with the steepest rises seen among high-risk groups. CONCLUSIONS: Syphilis infection is increasing among low- and high-risk groups in China, suggesting unsafe sexual behavior that may accelerate HIV transmission and challenge current syphilis prevention and control efforts.

China↗
PubMed2005

Short-term effects of artificial tears on visual performance in normal subjects.

PURPOSE: Temporal changes in tear film structure can distort the optical wavefront as it passes through the tear layer and reduce contrast sensitivity. Theoretically, any substance applied to the tear layer that alters its structure could affect contrast sensitivity. The purpose of this study is to investigate how different formulations of carboxymethylcellulose sodium (CMC) applied to the tear layer affect contrast sensitivity over time. Additionally, the visual effect of these drops applied over soft and rigid, gas-permeable contact lenses was also investigated. METHODS: Twenty normal subjects took part in this project. Refresh Celluvisc (Allergan, Irvine, CA, 1.0% high-viscosity CMC) was compared with Refresh Liquigel (Allergan, 1.0% total CMC made by blending 0.35% high-viscosity with 0.65% medium viscosity CMC). Ten of the subjects were habitual soft contact lens wearers and 10 were habitual gas-permeable lens wearers. The stimulus, viewed monocularly, was a stationary, vertically oriented, sine wave grating (14 CPD). A temporal, two-alternative, forced-choice paradigm combined with a self-paced method of limits was used to monitor threshold over time. After baseline data collection, a drop of the artificial tear was applied to the tear layer and the procedure continued for 30 min. This allowed continual tracking of the threshold. Data were collected while viewing the stimulus with the subject's contact lens or with their spectacle prescription. RESULTS: One drop of Liquigel or Celluvisc decreased contrast sensitivity for a 14 CPD sine wave grating (all p values < 0.005). This decrease in contrast sensitivity was observed during spectacle, soft contact lens, and gas-permeable contact lens wear. Soft contact lens wear resulted in a greater decrease in contrast sensitivity than spectacles when Liquigel was applied to the tear layer. None of the other conditions were different between contact lens and spectacle wear. The return to baseline contrast sensitivity was not significantly different between soft or gas-permeable contact lens wear and spectacles for either Liquigel or Celluvisc. In general, Celluvisc had a greater effect on visual performance than Liquigel. CONCLUSIONS: These results suggest that Liquigel and Celluvisc alter the tear layer and affect contrast sensitivity. The results agree with patient observations that Celluvisc causes a moderate amount of blur that gradually subsides. In such patients, the shorter duration of blur with Liquigel (about half that of Celluvisc) may be more acceptable. The technique of blending various viscosity CMC materials while maintaining the total CMC concentration of 1.0% may be beneficial in dry eye therapy without causing excessive blur to patients.

Adult↗
PubMed2005

Effect of artificial tears on visual performance in subjects with dry eye.

PURPOSE: Disruption of the anterior refracting surface of the eye (i.e., the tear layer) reduces visual performance. Tear layer breakup occurs soon after a blink in contact lens wearers and patients with dry eye. This study determined whether artificial tears stabilize the tear film and improve visual performance in contact lens wearers who also exhibit a dry eye. METHODS: Five subjects with mild to moderate dry eye (probably as a result of an evaporative dry eye) during spectacle and contact lens wear were fitted with a Focus Night & Day hydrogel lens for this study. A temporal, two-alternative, forced-choice paradigm was used to measure contrast sensitivity. The stimuli were vertically oriented sine wave gratings (between 0.5 and 14 cpd) presented for 16.67 msec. The stimuli were presented at two different times after blink detection: 2 sec after blink detection (i.e., before tear layer breakup) or 4 sec after tear film breakup. Four conditions were investigated at 4 sec after tear layer breakup: 1) without artificial tears added, 2) with Clerz2 (Alcon, Fort Worth, TX) instilled, 3) with Sensitive Eyes (Bausch & Lomb, Rochester, NY), and 4) with GenTeal (Novartis, Basel, Switzerland) applied. The artificial tears were instilled at 10-min intervals during the data collection. The short-term visual effects of drop instillation were also investigated by continually monitoring contrast sensitivity for a 14-cpd grating after a single-drop administration. RESULTS: High spatial frequency contrast sensitivity and visual acuity were found to be reduced after tear film breakup in the absence of supplementation with artificial tears. For the group data (and four of five subjects), the instillation of Sensitive Eyes improved the contrast sensitivity and visual acuity to the level attained before tear breakup, thus prolonging visual performance. Clerz2 and GenTeal did not produce any enhancement in visual performance. A short-term decrease in contrast sensitivity was also observed with a single administration of Clerz2 and GenTeal. CONCLUSIONS: This study indicates that there was a benefit of Bausch & Lomb Sensitive Eyes tear supplementation on visual performance in subjects with an evaporative dry eye. This may be the result of 1) aqueous supplementation in these subjects and/or 2) the minimal tear layer disruption found with Sensitive Eyes drop administration. The results suggest that practitioners need to identify those patients who can benefit from the use of appropriate artificial tear supplements.

Adult↗
PubMed2006

Measuring contrast sensitivity under different lighting conditions: comparison of three tests.

PURPOSE: The purpose of this study was to evaluate three psychophysical tests for the measurement of contrast sensitivity (CS) and disability glare (DG) at different luminance levels. METHODS: In 60 eyes of 60 individuals (group 1: 20 healthy eyes of young individuals; group 2: 20 healthy eyes of elderly subjects; group 3: 20 eyes with nuclear cataract), CS with best correction was measured twice with the Frankfurt-Freiburg Contrast and Acuity Test System (FF-CATS) and the Functional Acuity Contrast Test (FACT, 1.5 cycles per degree [cpd]) at 167 cd/m2 and 0.167 cd/m2, and with the Pelli-Robson Chart (PRC) at 100 cd/m2 with and without glare. Repeatability of test and retest, and discriminative ability between the different subgroups, were assessed for CS values. RESULTS: Maximum CS values varied across tests. In all groups, highest CS values were obtained with the photopic FF-CATS. For FACT scores at 1.5 cpd, there was a ceiling effect for young subjects. CS scores obtained with the PRC were the lowest. The PRC had the best test-retest repeatability of all tests. Under mesopic conditions with glare, reliability was generally lower; the FF-CATS had the highest repeatability of the mesopic tests. The FF-CATS discriminated best between the different groups for all conditions. CONCLUSIONS: There are large discrepancies in the test results between CS testing methods, especially under different lighting conditions. Results from different CS tests are not interchangeable.

Adult↗
PubMed2006

Visual performance of subjects wearing presbyopic contact lenses.

PURPOSE: The purpose of this study is to assess the visual performance of subjects wearing gas-permeable (GP) multifocal contact lenses, soft bifocal contact lenses, GP monovision lenses and spectacles. METHODS: The study included 32 subjects between the ages of 42 and 65 years wearing GP monovision, the Acuvue Bifocal (Vistakon), the Essentials GP Multifocal (Blanchard), and progressive addition lenses (PAL; spectacles group). There were eight subjects in each of these groups who were already wearing these modalities. Binocular low (18%) and high (95%) contrast acuities were recorded using the Bailey-Lovie chart; binocular contrast sensitivity from 1.5 to 18 cycles per degree (cpd) measured with the Vistech VCTS 6500 system, and monocular glare sensitivity at three luminance settings (400, 100, and 12 foot lamberts) was measured using the brightness acuity tester (BAT). Binocular near visual task performance (a modified version of letter counting method used in previous presbyopic studies) was also assessed. RESULTS: For the contact lens-wearing groups, subjects wearing GP multifocals provided the best binocular high and low contrast acuity followed by soft bifocal wearers. There was relative parity between the binocular high and low contrast acuity with PAL and GP multifocal wearers. Monovision acuity, measured binocularly, was determined to be lower than the other three groups with this difference being most significant with high contrast acuity. Among contact lens-wearing groups, it was observed that GP multifocal lens wearers experienced the lowest amount of monocular disability glare followed by soft bifocal wearers and monovision wearers. Subjects wearing soft bifocal lenses and monovision demonstrated slightly reduced binocular contrast sensitivity at all spatial frequencies. In the contact lens groups, GP multifocal lens wearers had the highest binocular contrast sensitivity at all spatial frequencies, on parity with PAL wearers, except at the highest spatial frequency (18 cpd) at which PAL wearers had better vision. Error scores for the binocular near visual task performance between the four groups revealed subjects with GP multifocal lenses and PAL wearers to have the least errors, followed by monovision users and then soft bifocal wearers with the most errors. CONCLUSION: Subjects wearing GP multifocals, soft bifocals, monovision, and PAL spectacles have good binocular contrast sensitivity, satisfactory binocular low and high contrast acuity, and increased sensitivity to glare. Presbyopic subjects requiring the use of contact lenses under dim light levels could benefit from GP multifocal lenses. Contrast and glare sensitivity evaluations provide significant information regarding the visual performance of the presbyopic contact lenses and should be included in regular presbyopic contact lens fitting.

Adult↗
PubMed2001

A multistep damage recognition mechanism for global genomic nucleotide excision repair.

A mammalian nucleotide excision repair (NER) factor, the XPC-HR23B complex, can specifically bind to certain DNA lesions and initiate the cell-free repair reaction. Here we describe a detailed analysis of its binding specificity using various DNA substrates, each containing a single defined lesion. A highly sensitive gel mobility shift assay revealed that XPC-HR23B specifically binds a small bubble structure with or without damaged bases, whereas dual incision takes place only when damage is present in the bubble. This is evidence that damage recognition for NER is accomplished through at least two steps; XPC-HR23B first binds to a site that has a DNA helix distortion, and then the presence of injured bases is verified prior to dual incision. Cyclobutane pyrimidine dimers (CPDs) were hardly recognized by XPC-HR23B, suggesting that additional factors may be required for CPD recognition. Although the presence of mismatched bases opposite a CPD potentiated XPC-HR23B binding, probably due to enhancement of the helix distortion, cell-free excision of such compound lesions was much more efficient than expected from the observed affinity for XPC-HR23B. This also suggests that additional factors and steps are required for the recognition of some types of lesions. A multistep mechanism of this sort may provide a molecular basis for ensuring the high level of damage discrimination that is required for global genomic NER.

Base Pair Mismatch↗
PubMed2005

Brassinosteroid homeostasis in Arabidopsis is ensured by feedback expressions of multiple genes involved in its metabolism.

Homeostasis of brassinosteroids (BRs) is essential for normal growth and development in higher plants. We examined responsiveness of 11 BR metabolic gene expressions to the decrease or increase of endogenous BR contents in Arabidopsis (Arabidopsis thaliana) to expand our knowledge of molecular mechanisms underlying BR homeostasis. Five BR-specific biosynthesis genes (DET2, DWF4, CPD, BR6ox1, and ROT3) and two sterol biosynthesis genes (FK and DWF5) were up-regulated in BR-depleted wild-type plants grown under brassinazole, a BR biosynthesis inhibitor. On the other hand, in BR-excessive wild-type plants that were fed with brassinolide, four BR-specific synthesis genes (DWF4, CPD, BR6ox1, and ROT3) and a sterol synthesis gene (DWF7) were down-regulated and a BR inactivation gene (BAS1) was up-regulated. However, their response to fluctuation of BR levels was highly reduced (DWF4) or nullified (the other eight genes) in a bri1 mutant. Taken together, our results imply that BR homeostasis is maintained through feedback expressions of multiple genes, each of which is involved not only in BR-specific biosynthesis and inactivation, but also in sterol biosynthesis. Our results also indicate that their feedback expressions are under the control of a BRI1-mediated signaling pathway. Moreover, a weak response in the mutant suggests that DWF4 alone is likely to be regulated in other way(s) in addition to BRI1 mediation.

Arabidopsis↗
PubMed1995

Ultraviolet Light Inhibition of Phytochrome-Induced Flavonoid Biosynthesis and DNA Photolyase Formation in Mustard Cotyledons (Sinapis alba L.).

In cotyledons of etiolated mustard (Sinapis alba L.) seedlings, phytochrome-far-red-absorbing form-induced flavonoid biosynthesis was found to be inhibited by short-term ultraviolet (UV) irradiations. UV inhibition was shown for the synthesis of quercetin, anthocyanin, and also for the accumulation of the mRNA for chalcone synthase, the key enzyme of this pathway. The UV effect was more pronounced on flavonoid biosynthesis, a process that selectively occurs in the epidermal layers, than on the synthesis of mRNA for chlorophyll a/b-binding protein localized in the mesophyll tissue. These UV inhibitory effects were accompanied by cyclobutane pyrimidine dimer (CPD) formation showing a linear fluence-response relationship. CPD formation and UV inhibition of flavonoid biosynthesis was found to be partially reversible by blue/UV-A light via DNA photolyase (PRE), allowing photoreactivation of the DNA by splitting of CPDs, which are the cause of the UV effect. Like flavonoid formation PRE was also induced by the far-red-absorbing form of phytochrome and induction was inhibited by UV. A potential risk of inhibition, in response to solar UV-B irradiation, was shown for anthocyanin formation. This inhibition, however, occurred only if photoreactivation was experimentally reduced. The PRE activity present in the etiolated seedlings (further increasing about 5-fold during light acclimatization) appears to be sufficient to prevent the persistence of CPDs even under conditions of high solar irradiation.

Journal Article↗
PubMed1996

Solar Ultraviolet-B Radiation Affects Seedling Emergence, DNA Integrity, Plant Morphology, Growth Rate, and Attractiveness to Herbivore Insects in Datura ferox.

To study functional relationships between the effects of solar ultraviolet-B radiation (UV-B) on different aspects of the physiology of a wild plant, we carried out exclusion experiments in the field with the summer annual Datura ferox L. Solar UV-B incident over Buenos Aires reduced daytime seedling emergence, inhibited stem elongation and leaf expansion, and tended to reduce biomass accumulation during early growth. However, UV-B had no effect on calculated net assimilation rate. Using a monoclonal antibody specific to the cyclobutane-pyrimidine dimer (CPD), we found that plants receiving full sunlight had more CPDs per unit of DNA than plants shielded from solar UV-B, but the positive correlation between UV-B and CPD burden tended to level off at high (near solar) UV-B levels. At our field site, Datura plants were consumed by leaf beetles (Coleoptera), and the proportion of plants attacked by insects declined with the amount of UV-B received during growth. Field experiments showed that plant exposure to solar UV-B reduced the likelihood of leaf beetle attack by one-half. Our results highlight the complexities associated with scaling plant responses to solar UV-B, because they show: (a) a lack of correspondence between UV-B effects on net assimilation rate and whole-plant growth rate, (b) nonlinear UV-B dose-response curves, and (c) UV-B effects of plant attractiveness to natural herbivores.

Journal Article↗
PubMed1997

Ultraviolet B-Sensitive Rice Cultivar Deficient in Cyclobutyl Pyrimidine Dimer Repair.

Repair of cyclobutyl pyrimidine dimers (CPDs) in DNA is essential in most organisms to prevent biological damage by ultraviolet (UV) light. In higher plants tested thus far, UV-sensitive strains had higher initial damage levels or deficient repair of nondimer DNA lesions but normal CPD repair. This suggested that CPDs might not be important for biological lesions. The photosynthetic apparatus has also been proposed as a critical target. We have analyzed CPD induction and repair in the UV-sensitive rice (Oryza sativa L.) cultivar Norin 1 and its close relative UV-resistant Sasanishiki using alkaline agarose gel electrophoresis. Norin 1 is deficient in cyclobutyl pyrimidine dimer photoreactivation and excision; thus, UV sensitivity correlates with deficient dimer repair.

Journal Article↗
PubMed1999

Identifying the management development needs of senior executives in Iran's teaching hospitals.

This research paper reports the findings of the first comprehensive survey of senior executives in Iran's teaching hospitals. It is based on an analysis identifying the continuing professional development (CPD) needs of the total population of the two senior levels of teaching hospitals management-presidents of physician-managers and administrative-managers. Four key areas of management knowledge were selected as the focus of the need identification: operational; financial; human resource; and organization change. The findings reveal a pent up demand for introductory level, formal knowledge in all four areas of management theory, to complement and extend the practical experience they have acquired in managing the complex environment of teaching hospitals. The paper goes on to propose a curriculum design and overall framework of provision to meet these genuinely felt CPD needs.

Curriculum↗
PubMed2005

Feature space interpretation of SVMs with indefinite kernels.

Kernel methods are becoming increasingly popular for various kinds of machine learning tasks, the most famous being the support vector machine (SVM) for classification. The SVM is well understood when using conditionally positive definite (cpd) kernel functions. However, in practice, non-cpd kernels arise and demand application in SVMs. The procedure of "plugging" these indefinite kernels in SVMs often yields good empirical classification results. However, they are hard to interpret due to missing geometrical and theoretical understanding. In this paper, we provide a step toward the comprehension of SVM classifiers in these situations. We give a geometric interpretation of SVMs with indefinite kernel functions. We show that such SVMs are optimal hyperplane classifiers not by margin maximization, but by minimization of distances between convex hulls in pseudo-Euclidean spaces. By this, we obtain a sound framework and motivation for indefinite SVMs. This interpretation is the basis for further theoretical analysis, e.g., investigating uniqueness, and for the derivation of practical guidelines like characterizing the suitability of indefinite SVMs.

Algorithms↗
PubMed2004

XPA gene-deficient, SCF-transgenic mice with epidermal melanin are resistant to UV-induced carcinogenesis.

Photobiologic investigations have been performed using animals without epidermal melanocytes. We developed xeroderma pigmentosum group A gene-deficient (XPA (-/-)), stem cell factor transgenic (SCF-Tg) mice, which one defective in nucleotide excision repair and have epidermal melanocytes, and investigated protective effects of epidermal melanin against UV-induced injuries. When irradiated to UVB, XPA (-/-) mice developed greatly enhanced responses including acute inflammation, cyclobutane pyrimidine dimer (CPD) formation, keratinocyte apoptosis, depletion of Langerhans cells and immunosuppression of contact hypersensitivity, but XPA (-/-), SCF-Tg mice showed much less responses to the same dose of UVB. XPA (-/-), SCF-Tg mice did not develop skin cancers after repeated exposures to UVB for 30 wk at a total dose of 72 J per cm(2), which induced a significant number of tumors even in wild-type, XPA (+/+) mice, and was lethal dose for XPA (-/-) mice. Dimethylbenz (alpha) anthracence (DMBA) induces DNA damages, which require XPA protein to be repaired. Topical application of DMBA produced a significant inflammation, CPD formation, apoptosis, immunosuppression, and skin cancers in XPA (-/-), SCF-Tg mice as well as XPA (-/-) mice. These findings indicate that epidermal melanin has a high ability to protect DNA damage by UVB radiation, and thereby, prevent UV-induced inflammation, immunosuppression, and carcinogenesis.

9,10-Dimethyl-1,2-benzanthracene↗