The incorporation of drugs into hair: relationship of hair color and melanin concentration to phencyclidine incorporation

Rodents with different hair pigmentation patterns were studied to evaluate the role of melanin in the incorporation of phencyclidine (PCP) into hair. There are two types of melanin in hair and other tissues: eumelanin, a brown-black pigment and pheomelanin, a reddish-yellow pigment. Sprague Dawley (SD; nonpigmented), Dark Agouti (DA; brown), Copenhagen (CP; brown hooded), Long Evans (LE; black hooded), and LBNF1 (deep brown) rats and Swiss-Webster (SW; nonpigmented), C57BL6 (black), and C57BL6 Ay/a (yellow) mice were administered PCP at 10 mg/kg/day for 5 days (n = 5 for each strain). Hair was collected either 14 (rats) or 35 (mice) days (mice) after beginning drug administration and analyzed for PCP, eumelanin, and pheomelanin. PCP concentrations in ng/mg (mean +/- SEM) were as follows: SD, 0.46 +/- 0.13; DA, 12.25 +/- 1.24; CP nonpigmented, 0.12 +/- 0.004; CP pigmented, 9.16 +/- 2.8; LE nonpigmented, 0.66 +/- 0.07; LE pigmented, 21.2 +/- 1.4; LBNF1, 21.64 +/- 3.8; SW, 0.48 +/- 0.36; C57 black, 11.0 +/- 4.03; and C57 yellow, 2.26 +/- 0.55. Eumelanin concentrations in microg/mg (mean +/- SEM) were as follows: DA, 20.50 +/- 1.58; CP pigmented, 19.43 +/- 0.40; LE pigmented, 17.56 +/- 0.61; LBNF1, 27.26 +/- 2.52; C57 black, 37.33 +/- 3.61; and C57 yellow, 1.76 +/- 0.02. Eumelanin was not detected in nonpigmented hair. Pheomelanin concentrations in microg/mg (mean +/- SEM) were as follows: DA, 0.09 +/- 0.00; CP pigmented, 0.20 +/- 0.03; LBNF1, 0.06 +/- 0.01; C57 black, 0.16 +/- 0.05; and C57 yellow, 29.16 +/- 0.97. Pheomelanin was not detected in nonpigmented or LE pigmented hair. These data demonstrate that PCP is incorporated into black hair to a greater extent than yellow or nonpigmented hair. There appears to be a linear relationship between the PCP concentration in hair and the ratio of eumelanin to pheomelanin. Our data suggest that despite variations in PCP concentration because of hair color, they may be normalized by using the ratio of eumelanin to pheomelanin rather than hair weight.     

Experimental study on external tibial rotation of the knee

We investigated the effect of varying concentration of 1-tyrosine and 1-cysteine in culture medium on melanin production by human skin melanocytes (skin phototype II/III). In addition to the analyses of dopa oxidase activity and total melanin, pheomelanin production in the cells was assessed by high-performance liquid chromatography determinations of pheomelanin degradation products, 3-aminotyrosine and 4-amino-3-hydroxyphenylalanine. As another marker for pheomelanin, melanosomal sulfur was determined by the use of X-ray microanalysis. With varying concentration of both amino acids, profound changes in the pigmentation patterns of the melanocytes were observed. A high concentration of 1-tyrosine (0.2 mM) was always connected with increased pigmentation. In combination with a low 1-cysteine content we saw an increase in tyrosinase activity and the highest melanin content. At high concentrations of both 1-tyrosine and 1-cysteine, the melanocytes showed reduced tyrosinase activity and they produced notably more pheomelanin. In case of the pheomelanin measurements by high-performance liquid chromatography and the sulfur detection with X-ray microanalysis, strongly increased concentrations were found when cells were maintained in high 1-tyrosine medium as compared with those grown with low 1-tyrosine. This was especially true for the combination with low 1-cysteine showing that the 1-tyrosine content of the medium strongly influences not only the eumelanin but also the pheomelanin production in the cultured melanocyte. It can be concluded that variations in the concentrations of 1-tyrosine and 1-cysteine in culture medium can be used to regulate the melanogenetic phenotype under in vitro conditions.     

Genetic studies of the mouse mutations mahogany and mahoganoid

The mouse mutations mahogany (mg) and mahoganoid (md) are negative modifiers of the Agouti coat color gene, which encodes a paracrine signaling molecule that induces a swithc in melanin synthesis from eumelanin to pheomelanin. Animals mutant for md or mg synthesize very little or no pheomelanin depending on Agouti gene background. The Agouti protein is normally expressed in the skin and acts as an antagonist of the melanocyte receptor for alpha-MSH (Mc1r); however, ectopic expression of Agouti causes obesity, possibly by antagonizing melanocortin receptors expressed in the brain. To investigate where md and mg lie in a genetic pathway with regard to Agouti and Mc1r signaling, we determined the effects of these mutations in animals that carried either a loss-of-function Mc1r mutation (recessive yellow, Mc1re) or a gain-of-function Agouti mutation (lethal yellow, Ay). We found that the Mc1re mutation suppressed the effects of md and mg, but that md and mg suppressed the effects of Ay on both coat color and obesity. Plasma levels of alpha-MSH and of ACTH were unaffected by md or mg. These results suggest that md and mg interfere directly with Agouti signaling, possibly at the level of protein production or receptor regulation.     

Structural analysis of memory traces in children from 4 to 10 years of age.

In 2 experiments, items from 4 (or 8) semantic categories were presented in 4 (or 8) colors located at 4 (or 8) spatial positions. In a recall task, a total of 48 4-, 7-, and 10-yr-olds were given semantic, color, and locational cues. The probability of successful cued recall to each type of cue and cue combination was used to estimate the proportion of memory traces that contained the various types of information. Although recall increased with age, the relative effectiveness of the 3 types of cues did not, and the estimated proportion of memory traces for the set of items that contained semantic information was higher than the estimated proportion having color and locational information. Retention of one type of cue information was not independent of retention of other types of cue information; Ss of all ages tended to retain either none or more than 1 of the 3 kinds of information. (21 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Photoprotective actions of natural and synthetic melanins

Melanins are thought to be important modulators of photochemistry in skin. Eumelanin, a black-brown pigment, is believed to protect against UV-induced photodamage, whereas pheomelanin, a red-yellow pigment, is believed to possess photosensitizing properties. To investigate the hypothesized dichotomy of melanins as both photoprotectants and photosensitizers, we examined the effects of melanins on UV-induced liposomal lipid peroxidation. Sepia melanin, a representative eumelanin, and both red hair pheomelanin and synthetic pheomelanin were employed in these studies. Both eumelanin and pheomelanin inhibited UVA/B- and UVA-induced liposomal lipid peroxidation in a concentration-dependent manner as measured by inhibition of conjugated diene formation. No change in protective properties of the melanins was observed in the presence of saturating levels of O2 during UVA irradiation. Pheomelanin irradiated with UVA/B or UVA induced superoxide-catalyzed reduction of nitroblue tetrazolium, whereas eumelanin did not. Melanins are known to bind various metals, and we examined the effect of iron on the photoproperties of melanins. Eumelanin complexed with Fe(III) did not inhibit UVA/B-induced lipid peroxidation, whereas pheomelanin complexed with Fe(III) stimulated UVA/B-induced lipid peroxidation. Thus, complexation with iron reversed the antioxidant effect of eumelanin and converted pheomelanin into a prooxidant. Analysis of lipid peroxidation products indicated that the oxidation was mediated by free radicals rather than by singlet oxygen. These data indicate that both eumelanin and pheomelanin exert antioxidant effects against UV-induced lipid peroxidation but that the prooxidant activities of pheomelanin result from pheomelanin-metal complexation.     

(Pheo)melanin photosensitizes UVA-induced DNA damage in cultured human melanocytes

The question of whether melanins are photoprotecting and/or photosensitizing in human skin cells continues to be debated. To evaluate the role of melanin upon UVA irradiation, DNA single-strand breaks (ssb) were measured in human melanocytes differing only in the amount of pigment produced by culturing at two different concentrations, basic (0.01 mM) or high (0.2 mM), of L-tyrosine, the main precursor of melanin. In parallel, pheo- and total melanin contents of the cells were determined. Identical experiments were performed with two melanocyte cultures derived from a skin type I and a skin type VI individual. For the first time the correlation between UVA-induced genotoxicity and pheo-/total melanin content has been investigated. We observed that cultured in basic medium, the skin type VI melanocytes contained 10 times more total melanin and about seven times more pheomelanin than the skin type I melanocytes. Elevation of tyrosine level in the culture medium resulted in an increase of both pheo- and total melanin levels in both melanocyte cultures; however, the melanin composition of skin type I melanocytes became more pheomelanogenic, whereas that of skin type VI melanocytes remained the same. The skin type VI melanocytes cultured in basic medium demonstrated a very high sensitivity (1.18 ssb per 10(10) Da per kJ per m2) toward UVA that is probably related to their high pheo- and total melanin content. Their UVA sensitivity, however, did not change after increasing their melanin content by culturing at high tyrosine concentration. In contrast, the skin type I melanocytes demonstrated a low sensitivity (0.04 ssb per 10(10) Da per kJ per m2) toward UVA when cultured in basic medium, but increasing their melanin content resulted in a 3-fold increase in their UVA sensitivity (0.13 ssb per 10(10) Da per kJ per m2). These results demonstrate that UVA-irradiated cultured human melanocytes are photosensitized by their own synthesized chromophores, most likely pheomelanin and/or melanin intermediates.     

Color constancy under natural and artificial illumination

Color constancy was studied under conditions simulating either natural or extremely artificial illumination. Four test illuminants were used: two broadband phases of daylight (correlated color temperatures 4000 and 25,000 K) and two spectrally impoverished metamers of these lights, each consisting of only two wavelengths. A computer controlled color monitor was used for reproducing the chromaticities and luminances of an array of Munsell color samples rendered under these illuminants. An asymmetric haploscopic matching paradigm was used in which the same stimulus pattern, either illuminated by one of the test illuminants, or by a standard broadband daylight (D65), was alternately presented to the left and right eye. Subjects adjusted the RGB settings of the samples seen under D65 (match condition), to match the appearance of the color samples seen under the test illuminant. The results show the expected failure of color constancy under two-wavelengths illumination, and approximate color constancy under natural illumination. Quantitative predictions of the results were made on the basis of two different models, a computational model for recovering surface reflectance, and a model that assumes the color response to be determined by cone-specific contrast and absolute level of stimulation (Lucassen & Walraven, 1993). The latter model was found to provide somewhat more accurate predictions, under all illuminant conditions.     

The effects of improved diets on the daily intake of environmental contaminants as calculated from personal food consumption data, by Monte Carlo simulation

In a previous paper, we discussed the Estimated Ecological Daily Intake (EEDI), which is a new method for the estimating daily intake of environmental contaminants based on individual food consumption data. This method makes it possible to identify high-risk cases, using a Monte Carlo simulation for varying contamination levels in each food item and permits epidemiological assessment of the individual, rather than the population, intake of environmental contaminants. We attempted to identify those contaminants whose maximum dietary levels were most commonly exceeded. The results obtained were as follows: 1) After a 1,000-fold extrapolation, performed for each person and contaminant, some cases exceeded allowable maximums in dieldrin, lead, cadmium, and total mercury. In dieldrin and lead intake, few cases exceeded dieldrin and lead maximums by a factor of 2 or 3, but in the cases of cadmium and total mercury, individual maximum intake was significantly exceeded. 2) After estimating a high-risk individual's times of exceeding the allowance in cadmium intake with dietary improvement, we found a 10.5% excess intake after 40% improvement. Clearly, the issue of environmental contaminants exposure due to dietary intake is a significant one.     

Another view of schizophrenia subtypes. A report from the international pilot study of schizophrenia

We studied respiratory mechanics in young volunteers before and after 5-wk training programs limited to the ventilatory muscles. Four strength trainers (S) performed repeated static maximum inspiratory and expiratory maneuvers against obstructed airways. Four endurance trainers (E) performed voluntary normocarbic hyperpnea to exhaustion. Subjects spent 30-45 min each day in these exercises, 5 days a week. Four control subjects (C) did no training. We attempted to minimize the effect of learning. S increased pressure maximums by about 55%, but vital capacity and total lung capacity by only about 4%. Initially all subjects could sustain hyperpnea at about 81% of their control 15-s maximum voluntary ventilation (MVV) for 15 min; E increased this to about 96% and increased their MVV by 14% as well. No other statistically significant changes were recognized in any group. We conclude that ventilatory muscle strength or endurance can be specifically increased by appropriate ventilatory muscle training programs.     

Septicemia in the newborn due to gram-negative bacilli. Risk factors, clinical symptoms, and hematologic changes

The case histories of 17 newborns developing septic shock due to gram-negative bacilli were studied for pre- and perinatal risk factors, clinical symptoms, and hematologic changes. Immaturity, resuscitation procedures, and hypothermia on admission were found to be the risk factors most frequently preceding septicemia. A skin color fading and changing from reddish-pink to yellow-green was the most early noticeable clinical symptom in all patients. The total leukocyte counts as well as the relative proportion of bands increased significantly at the onset of illness. When septicemia advanced, a marked drop of leukocytes was found, while the relative proportion of bands increased further. Only 1 in 12 cases showed a decrease in the platelet counts at the height of septicemia. A procedure for the early diagnosis of a neonatal septicemia is proposed: (1) Registration of perinatal risk factors. (2) With perinatal risk factors a skilled and attentive clinical observation is necessary. Particular attention should be paid to changes of skin color. (3) White blood cell picture: (a) every day in patients with perinatal risk factors and (b) every 6 h in patients showing suspicious symptoms.     

Linkage of circulating eosinophils to markers on chromosome 5q

Although peripheral blood eosinophilia is strongly associated with the risk of developing asthma, genetic determinants of eosinophilia have not been extensively studied. We used sib-pair analysis to assess linkage of circulating eosinophils (as a percent of total white blood cells [WBC]) to nine markers located in chromosome 5q31-33. The study was divided into two phases. Of 246 sib pairs available for the first phase, 35 were classified as low concordant (LC) (both sibs had <= 2% circulating eosinophils), 18 were defined as high concordant (HC) (both sibs had 5% or more circulating eosinophils), and 26 were defined as discordant (one sib had <= 2% and the other sib had 5% or more circulating eosinophils). Significant evidence for linkage among low concordant sib pairs was found for several markers in the region under study, with a peak for marker D5S500 (proportion of alleles shared identical by descent [ibd] = 0.68 +/- 0.05 [mean +/- SE], p = 0.0004). A cross-validating study was done in which an additional 19 sib pairs that were low concordant for circulating eosinophils were studied. Evidence for linkage was also observed in this subset. Results were independent of current wheezing, total serum IgE levels, and other potential confounders. A multipoint analysis done for all low-concordant sib pairs available showed that the maximal logarithm of the odds favoring genetic linkage (LOD) score (2.4, p = 0.0004) was observed in correspondence with marker D5S658. We conclude that a locus or loci may be present in chromosome 5q31-33 that controls for circulating eosinophils as a proportion of total WBC.     

The use of a photoprotective agent to increase the color stability of a tinted extraoral prosthetic silicone

PURPOSE: This study investigated the use of ultraviolet-absorbing or photoprotective agents as a method of decreasing the color changes caused by ultraviolet radiation on an intrinsically tinted facial prosthetic material. MATERIALS AND METHODS: Silastic MDX 4-4210 (Dow Corning Corp, Midland, MI) was the facial prosthetic material studied. It was intrinsically tinted with talc and nylon flock to approximate the color of skin. Three brands of commercially available sunscreens with sun protective factor (SPF) of 15 were placed on the surface of the cured silicone samples. The samples were rotated in an ultraviolet radiation chamber for 300 hours. A control group was placed in the dark for 300 hours. The second phase of the experiment had para-aminobenzoic acid (PABA) added to the tinted silicone. All samples were measured with a spectrophotometer at the beginning and at the end of 300 hours, and a delta E was obtained. RESULTS: None of the sunscreens provided any ultraviolet radiation protection to the silicone. The addition of PABA caused a significant color degradation of the silicone. CONCLUSIONS: No photoprotective agent tested provided any significant level of ultraviolet radiation protection for silastic MDX 4-4210.     

Effect of sexual abstinence on the proportion of X-bearing sperm as assessed by multicolor fluorescent in situ hybridization

OBJECTIVE: To document the relation between sexual abstinence and the proportion of X-bearing sperm in the ejaculate. DESIGN: Prospective cohort study. SETTING: Medical college. PATIENT(S): Ten normospermic men, aged 30 to 40 years, provided two semen samples: the first sample was obtained 1.0 to 1.5 days after ejaculation; the second, 7 to 10 days after ejaculation. INTERVENTION(S): Abstinence. MAIN OUTCOME MEASURE(S): Proportion of X- and Y-bearing sperm in two ejaculates. RESULT(S): Multicolor fluorescent in situ hybridization using directly labeled alpha-satellite probes specific for chromosomes 18, X and Y were used to analyze 40,273 sperm. After 1.0 to 1.5 days of abstinence, there were 47.6% +/- 1.7% (mean +/- SD) X-bearing sperm, and after 7 to 10 days of abstinence, there were 49.6% +/- 2.1% X-bearing sperm. The X:Y ratio increased marginally from 0.905 to 0.981. CONCLUSION(S): Sexual abstinence marginally increases the proportion of X-bearing sperm in the ejaculate as assessed by multicolor fluorescent in situ hybridization. This change of borderline statistical significance probably has little impact on the secondary sex ratio.     

Oleamide potentiates benzodiazepine-sensitive gamma-aminobutyric acid receptor activity but does not alter minimum alveolar anesthetic concentration

Short-term exposure to ozone at peak ambient levels induces neutrophil influx and impairs lung function in healthy humans. In order to investigate the mechanisms contributing to neutrophil recruitment and to examine the role of T-cells in the acute inflammatory response, we exposed 12 healthy humans to 0.2 parts per million (ppm) of ozone and filtered air on two separate occasions for 2 h with intermittent periods of rest and exercise (minute ventilation = 30 L x min(-1)). Fibreoptic bronchoscopy was performed 6 h after the end of exposures. Total protein, tryptase, histamine, myeloperoxidase, interleukin (IL)-8 and growth-related oncogene-alpha (Gro-alpha) were measured and total and differential cell counts were performed in bronchoalveolar lavage (BAL) fluid. Flow cytometry was performed on BAL cells to study total T-cells, T-cell receptors (alphabeta and gammadelta), T-cell subsets (CD4+ and CD8+ cells) and activated T-cell subsets (CD25+). Using immunohistochemistry, neutrophils, mast cells, total T-cell numbers, T-cell subsets, CD25+ T-cells and leukocyte endothelial adhesion molecules including P-selectin, E-selectin, intercellular adhesion molecule (ICAM)-1 and vascular adhesion molecule (VCAM)-1 were quantified in the bronchial biopsies. Paired samples were available from nine subjects. Following ozone exposure there was a threefold increase in the proportion of polymorphonuclear neutrophils (PMNs) (p=0.07) and epithelial cells (p=0.05) in BAL fluid. This was accompanied by increased concentrations of IL-8 (p=0.01), Gro-alpha (p=0.05) and total protein (p=0.058). A significant positive correlation was demonstrated between the two chemokines and proportion of PMNs in BAL fluid. After ozone exposure there was a significant decrease in the CD4/CD8 ratio (p=0.05) and the proportion of activated CD4+ (p=0.01) and CD8+ T-cells (p=0.04). However, no significant changes were demonstrable in any of the inflammatory markers studied in the biopsies. Short-term exposure of healthy humans to 0.2 ppm ozone induced a neutrophil influx in peripheral airways at 6 h post exposure, but no apparent inflammatory response in proximal airways. This response seems to be mediated at least in part by interleukin-8 and growth-related oncogene-alpha.     

Effect of direct reduced iron on alumina activity in electric arc furnace slags

Abstract

Test trials were conducted in a 70 t ultrahigh power (UHP) electric arc furnace. The proportion of direct reduced iron (DRI) in the charge varied between 40 and 95%. Slag samples were taken at various time intervals and analysed. The analyses were used for estimating the activity of alumina in the slag. The activity was correlated with the basicity, temperature and DRI proportion in the charge. The results of correlation show that the activity is mainly dependent on the basicity of the slag. It is inversely proportional to the basicity and increases as the temperature rises. The activity increases by 3·8×10- 4 for every 10% increase in DRI proportion in the charge.     

Echocardiographic hemodynamic and morphometric predictors of survival after two-ventricle repair in infants with critical aortic stenosis

OBJECTIVES: The purpose of this study was to identify echocardiographic hemodynamic and morphometric factors that would predict which infants with critical aortic stenosis could undergo relief of left ventricular outflow obstruction as opposed to the Norwood procedure. BACKGROUND: Echocardiographic predictors of survival in infants with critical aortic stenosis after two-ventricle repair have been mainly limited to morphometric factors, which have limitations. Echocardiographic hemodynamic predictors of survival in these patients have not previously been studied. METHODS: Doppler color flow mapping and pulsed Doppler techniques were used to obtain hemodynamic measurements of flow in the ascending, transverse and descending aorta, the ductus arteriosus, and across the aortic and mitral valves in infants with critical aortic stenosis. Morphometric measurements of the left heart structures were obtained, and comparisons were made between survivors and nonsurvivors for the hemodynamic and morphometric factors. RESULTS: Twenty-eight infants (mean age 1 +/- .6 days, mean weight 3.6 +/- .6 kg) with critical aortic stenosis were evaluated. Nineteen had a two-ventricle repair initially attempted, and nine had a Norwood operation. Among the patients with a two-ventricle repair, the hemodynamic factors associated with survival after two-ventricle repair included predominant or total antegrade flow in the ascending (p < 0.01) and transverse aorta (p < 0.05). Aortic valve gradient, mitral valve inflow and direction of flow in the ductus arteriosus and descending aorta were unrelated to outcome. The morphometric factors associated with survival after two-ventricle repair included the indexed aortic annulus (p < 0.0002), aortic root (p < 0.003), ascending aorta (p < 0.008) and left ventricular long-axis length (p < 0.01). Left ventricular volume, mass, ejection fraction and mitral valve area were not related to outcome after two-ventricle repair. CONCLUSIONS: In infants with critical aortic stenosis, predominant or total antegrade flow in the ascending and transverse aorta was associated with survival after two-ventricle repair. Determination of a one- versus two-ventricle repair remains a complex issue in infants with critical aortic stenosis. In addition to established morphometric predictors, hemodynamic information on the direction of flow in the aorta may help to define candidates for the Norwood operation.     

Is fatty liver induction a general feature of the administration of foreign sulfhydryl compounds?

Adequate N retention and growth have been demonstrated in children consuming diets in which the total daily protein is fed in a single meal, energy intake being spread over a 14 hour period. To elucidate how adequate protein nutriture continues when protein is not consumed in parallel to energy, plasma free amino acids were measured in 11 children fed a casein-modified cow's milk based diet providing all protein (6.4% of calories) in one feeding, while energy was evenly distributed among five feedings. Children were fed at 0800 hours, 1200 hours, 1500 hours (protein-containing meal), 1900 hours, and 2200 hours. Fasting plasma aminograms were determined in all 11 children. During a long-term growth study with the diet, six children had additional determinations 3 and 4 hours after the first feeding on the same day on which the fasting sample was obtained; samples prior to and 3 and 4 hours after the 1500 hour feeding were obtained on a different day. In a seventh child, all six samples were obtained on a single day. Fasting values for total amino acids (TAA), total essential amino acids (TEAA) and TEAA/TAA, Val, Ile and Pro were elevated in most cases, a pattern seen in children fed high protein diets. The 1100 hour and 1200 hour samples showed a marked decrease in TAA, TEAA and TEAA/TAA. A further drop at 1500 hour produced a pattern characteristic of protein deficiency. Following the protein containing meal, TAA increased 50-100%, TEAA 100-200%, with disproportionate increases in Leu, Ile, Val and Pro. The persistence of this pattern in some cases up to 17 hours suggested that EAA were available for protein synthesis when additional energy was subsequently consumed. An aminogram characteristic of protein deficiency was seen only 18-20 hours after the last protein intake.     

Genetic and environmental contributions to size, color, shape, and other characteristics of melanocytic naevi in a sample of adolescent twins

The presence of melanocytic naevi is the strongest known risk factor for malignant melanoma. We have developed a computer imaging system with which it is possible to make quantitative measures of the size, color, and shape of pigmented lesions. The objective of this study was to examine the genetic and environmental contributions to these characteristics of naevi as measured by computer image analysis in a sample of adolescent twins. We captured video images of the 5 most atypical pigmented skin lesions (i.e., the largest, darkest, or most irregularly shaped) on each individual from 322 Australian adolescent twin pairs. Features extracted by computer image analysis for each lesion included color, size, symmetry, elongation, boundary irregularity, and edge distinctness. We found major genetic influences on the color and size of lesions accounting for between 40 and 80% of total variance. There were significant components of shared environmental influence (22-45% of total variance) for the color variables, with sun exposure the most obvious explanation. Differences between individuals in naevus color and size are largely genetic in origin although there are significant environmental contributions to color as well.