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PubMed1983

Hair-bearing neck flap for upper-lip reconstruction in the male.

Reconstruction of the upper lip resulting in a hair-bearing area and a non-hair-bearing lining is described in two cases of full-thickness lip defects. A unipedicled neck flap was used in one case and a bipedicled neck flap in the other, both comprised of hair-bearing and adjacent non-hair-bearing areas. The neck flap has the advantages of providing the two layers of the lip, and the reconstructed lip is not too thick and is mobile and pliable, and the hair resembles lip hair in color, density, and quality. The multiple operative procedures can be performed under local anesthetic.

Adult↗
PubMed1993

Analysis of nicotine content of hair for assessing individual cigarette-smoking behavior.

The concentration of nicotine in hair was measured by a capillary gas chromatograph with a nitrogen-phosphorus detector after hair was dissolved in 2.5 N sodium hydroxide and nicotine was extracted using diethyl ether. In hair samples obtained from 36 smokers, who had smoked > or = 3 years, there was a significant positive correlation between the concentration of nicotine and the number of cigarettes consumed daily (r = 0.685; p < 0.001). The nicotine content of white hair was much less than that of black hair collected from the same subjects with grizzled hair. The above findings were confirmed by an animal experiment, in which nicotine (0.2, 0.6, and 2 mg/kg/day for 2 weeks) was administered intraperitoneally to pigmented rats whose hair had been removed beforehand by plucking from an area of the back of each rat. The hair which grew back in the denuded area was plucked and collected one week after the last administration of nicotine. The nicotine concentration in the brown hair of the back correlated with the given dose (r = 0.824; p < 0.001). In a separate experiment, hairs were removed from areas of back and thorax, and nicotine delivered to the rats for 4 weeks by an osmotic pump implanted under the skin, showing that the concentration in the whitish hair was much lower than that in brown hair. Finally, hair samples were collected from 14 subjects who had participated in a smoking cessation program over 6 months and who abstained from cigarette smoking. The axial distribution of nicotine along the hair shafts was determined for each subject.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1995

The histological and immunohistochemical changes in the skin of patients with melanoma who develop changes in skin pigmentation following immunotherapy.

The histological and immunocytochemical appearances of skin with altered pigmentation from two patients receiving chemoimmunotherapy for melanoma were examined. In both patients, there was a clinical response to treatment coincident with depigmentation of skin and hair. Skin biopsies showed extensive infiltration with CD8+ and CD4+ lymphocytes rather than CD57+ in the depigmented areas suggestive of a specific MHC-related cytotoxic T-cell activity against melanocytes. In keeping with this, MHCII expression was markedly up-regulated. These observations suggest the development of a simultaneous anti-tumour and anti-melanocyte immune response stimulated by chemoimmunotherapy, possibly against the same or similar antigens.

Adult↗
PubMed1998

Phaeomelanin versus eumelanin as a chemical indicator of ultraviolet sensitivity in fair-skinned subjects at high risk for melanoma: a pilot study.

It is now generally agreed that solar exposure is a major external factor in the causation of cutaneous melanoma in light skinned populations with red hair and a marked susceptibility to the acute effects of ultraviolet (UV) radiation. In the present study, we investigated the existence of a possible relationship between hair melanin composition and minimal erythema dose (MED), as an indicator of UV sensitivity, in a group of 15 healthy red-haired subjects aged 20-46 years. In spite of comparable skin and hair colour, marked variations were observed in the MED values as well as in the hair melanin composition. Phaeomelanin levels varied in the range 0.026-0.53% w/w and were generally comparable to or higher than eumelanin levels (0.042-0.17% w/w). No significant relationship was found between MED values and phaeomelanin, eumelanin or total melanin (eumelanin plus phaeomelanin) content. Notably, however, a gross positive correlation was found between the eumelanin/phaeomelanin ratio and the MED values. These results would suggest that a high UV sensitivity is associated with high phaeomelanin and low eumelanin levels, and point to the eumelanin/phaeomelanin ratio as a novel chemical parameter that could be used for predicting individuals at high risk for skin cancer and melanoma.

Adult↗
PubMed2001

Development of an integrated method of skin phenotype measurement using the melanins.

Different types of melanin pigments have recently been identified and recognized as critical determinants of the photosensitivity of individuals. Eumelanin, the black to brown melanin pigments, are believed to protect against ultraviolet-induced cell damage, while phaeomelanin, the reddish brown variant, is thought to be photosensitizing. The relative, qualitative and absolute amount of melanin production under stimulation of solar radiation is likely to be genetically determined. The hypothesis of this study is that determination of these values can help in identifying those people who are less protected. However, these techniques must be evaluated at a population level and against traditional epidemiological measures. We assessed the amount and type of melanin in 195 subjects in four centres across Europe, relating the results to epidemiological measures such as skin characteristics, history of sunburns and number of naevi. The most important finding was that eumelanin and phaeomelanin have very different distributions in the population, being associated with other phenotype characteristics with different patterns. The relationship between phaeomelanin and eumelanin is linearly inverse in the range from black to dark blonde hair colour, while it is weakly directly proportional in the range from dark blonde to light blonde, with people with red hair showing a peculiar pattern. Phaeomelanin rather than eumelanin seemed to be independent of other skin characteristics. The results show the feasibility of a further study with an appropriate case-control design and accurate determination of melanin.

Chromatography, High Pressure Liquid↗
PubMed2004

Constitutional and environmental risk factors for cutaneous melanoma in an Italian population. A case-control study.

The aim of this study was to determine the relative risk for cutaneous melanoma associated with phenotypic and environmental variables in a population in central Italy and to assess how the combination of the different risk factors contributes to the overall risk for melanoma. We performed a case-control study of 100 patients with sporadic cutaneous melanoma and 200 controls matched for sex, age, ethnicity and residential area. Individuals were interviewed concerning pigmentary traits and sun exposure, and underwent a total body skin examination. Logistic regression models were used to evaluate the association between cutaneous melanoma and constitutional and environmental variables. The strongest risk factors were prolonged recreational sun exposure (odds ratio [OR] 5.010, 95% confidence interval [CI] 2.110-11.891), the presence of clinically atypical naevi (OR 4.916, 95% CI 2.496-9.995) and the presence of >50 common melanocytic naevi (OR 4.684, 95% CI 2.442-9.231). In addition, occupational sun exposure (OR 2.573, 95% CI 1.399-4.732), light brown hair (OR 2.336, 95% CI 1.328-4.138), high density of solar lentigos and/or actinic keratoses (OR 1.824, 95% CI 1.0-3.510) and type II, fair skin (OR 1.815, 95% CI 1.031-3.193) and blue eyes (OR 1.757, 95% CI 1.0-3.477) were each significantly associated with cutaneous melanoma risk. The combination of individual strong risk factors was associated with up to a 46-fold increase in the risk for cutaneous melanoma. Selected pigmentary traits, sun exposure and melanocytic naevi, individually and in combination, are important risk factors for cutaneous melanoma in an Italian population.

Adolescent↗
PubMed1998

Branchio-oculo-facial syndrome associated with a white forelock.

We report a father and his daughter with branchio-oculo-facial syndrome. Since birth the father, and to a lesser extent his daughter, demonstrated a white forelock which has not been reported before as associated with this syndrome. The analysis of the second to the eighth exon of PAX3 genes did not reveal any abnormality. The analysis of the EYA1 gene is proposed as well.

Abnormalities, Multiple↗
PubMed2004

Superstition and post-tonsillectomy hemorrhage.

OBJECTIVES/HYPOTHESIS: The objective was to determine whether post-tonsillectomy hemorrhages occur more frequently in redheaded children, in patterns of threes, on Friday-the-13th days, or with the full moon. STUDY DESIGN: Case-control analysis. METHODS: The authors performed multiple statistical analyses of all children undergoing tonsillectomy at Temple University Children's Medical Center (Philadelphia, PA) during a 29-month period. Children readmitted to the hospital with or without surgical control of bleeding were compared with children who did not bleed. Relation of post-tonsillectomy hemorrhages to the phase of the moon was evaluated using a standard normal deviate. The frequency of surgery performed on Friday-the-13th days was compared with a differently dated Friday chosen at random. Clusters of three hemorrhages in a 7-day period were recorded. Families of children were contacted and asked whether their child had red hair. A chi analysis compared redheaded and non-redheaded tonsillectomy patients. RESULTS: Twenty-eight of 589 tonsillectomy cases performed required readmission for bleeding events. Twenty tonsillectomies occurred on a full-moon day, resulting in one bleeding event. One cluster of three post-tonsillectomy hemorrhages occurred in a 7-day period. Four of the children who bled had red hair. Two tonsillectomies occurred on Friday the 13th, with no associated hemorrhage. Statistical analysis revealed a random pattern to post-tonsillectomy hemorrhage. CONCLUSION: Post-tonsillectomy hemorrhages do not occur in clusters of three and are not more frequent with the full moon or on Friday the 13th. The bleeding rate among children with red hair is similar to that of non-redheaded children.

Case-Control Studies↗
PubMed1996

Density-dependent selection in a fluctuating ungulate population.

Despite considerable theoretical interest no direct examples of density-dependent natural selection acting on simple polymorphic variation have been documented in a natural population. Here we show that the magnitude of selective differences in survival between phenotypes in two conspicuous polymorphisms of coat colour and horn type in Soay sheep Ovis aries living on St Kilda, Scotland are associated with marked changes in population density. Selection is strongest in years of high density but weak in years of low density. In addition to direct observations of density-dependent 'soft' selection in a natural population, the analysis revealed that the level of overcompensatory mortality (responsible for promoting population instability) was higher after accounting for genetic variation in the coat and horn morph traits. The results emphasize the importance of understanding the interaction between selection and population demography for both genetic and ecological studies of natural populations.

Animals↗
PubMed1981

On pattern formation mechanisms for lepidopteran wing patterns and mammalian coat markings.

The patterns on wings of Lepidoptera can be generated with a few pattern elements, but no mechanism has been suggested for producing them. I consider two of the basic patterns, namely, central symmetry and dependent patterns. A biochemically plausible model mechanism is proposed for generating major aspects of these patterns, based on a diffusing morphogen that activates a gene or colour-specific enzyme in a threshold manner to generate a stable heterogeneous spatial pattern. The model is applied to the determination stream hypothesis of Kühn & von Engelhardt (Wilhelm Roux Arch. Entw Mech. Org. 130, 660 (1933)), and results from the model compared with their microcautery experiments on the pupal wing of Ephestia kühniella. In the case of dependent patterns, results are compared with patterns on specific Papilionidae. For the same mechanism and a fixed set of parameters I demonstrate the important roles of geometry and scale on the spatial patterns obtained. The results and evidence presented here suggest the existence of diffusion fields of the order of several millimetres, which are very much larger than most embryonic fields. The existence of zones of polarizing activity is also indicated. Colour patterns on animals are considered to be genetically determined, but the mechanism is not known. I have previously suggested that a single mechanism that can exhibit an infinite variety of patterns is a candidate for that mechanism, and proposed that a reaction-diffusion system that can be diffusively driven unstable could be responsible for the laying down of the spacing patterns that generates the pre-pattern for animal coat markings. For illustrative purposes I consider, a practical reaction mechanism, which exhibits substrate inhibition, and show that the geometry and scale of the domain (part of the epidermis) play a crucial role in the structural patterns that result. Patterns are obtained for a selection of geometries, and general features are related to the coat colour distribution in the spotted Felidae, giraffe, zebra and other animals. The patterns depend on the initial conditions, but for a given geometry and scale are qualitatively similar, a positive feature of the model and a necessary model attribute in view of the pattern individuality on animals of the same species.

Animals↗
PubMed1989

Host genetic control of incubation periods of Creutzfeldt-Jakob disease in mice.

Host genetic control of the incubation period of Creutzfeldt-Jakob disease (CJD) was studied using various inbred strains of mice, including B10 congenic strains. Various incubation periods were found in mice injected either intracerebrally or intraperitoneally with the Fukuoka 1 strain of the CJD agent; NZW/Sea and A/JJms had the shortest, and B10.AKM/Ola and C57BL/6J the longest, incubation periods. Length of the CJD incubation period did not correlate with the genetic markers tested, i.e. the murine major histocompatibility (H-2) complex (which has previously been reported to be linked to a gene influencing CJD incubation period in mice), coat colour or sex genes. In NZW/Sea x C57BL/6J F1 hybrid mice the CJD incubation periods were similar to that of the parent with the longest incubation period. Incubation periods of the backcross progeny from F1 and NZW/Sea were intermediate between those of the parental mice and had a unimodal distribution pattern. A similar observation was made on the progeny of the A/JJms x C57BL/6J mating. On the other hand, the length of incubation period for the NZW/Sea x B10.AKM/Ola F1 hybrid fell between those for the two parents and the NZW/Sea x A/JJms F1 hybrid had a significantly longer incubation period than those of the two parents. These results suggest that polygenes probably control the length of the CJD incubation period in mice.

Alleles↗
PubMed1993

Cloning of the mouse agouti gene predicts a secreted protein ubiquitously expressed in mice carrying the lethal yellow mutation.

The mouse agouti gene controls the deposition of yellow and black pigment in developing hairs. Several dominant alleles, including lethal yellow (Ay), result in the exclusive production of yellow pigment and have pleiotropic effects that include obesity and increased tumor susceptibility. In an interspecific backcross, we established genetic limits for the agouti gene and found that the Ay and the lethal non-agouti (ax) allele were not separated from a previously identified probe at the breakpoint of the Is1GsO chromosomal rearrangement. Using the Is1GsO probe, we isolated the agouti gene, and find that it has the potential to code for a secreted protein expressed in hair follicles and the epidermis, and that the level of expression correlates with the synthesis of yellow pigment. In the Ay mutation, there is a chromosomal rearrangement that results in the production of a chimeric RNA expressed in nearly every tissue of the body. The 5' portion of this chimeric RNA contains highly expressed novel 5' sequences, but the 3' portion retains the protein-coding potential of the nonmutant allele. We speculate that dominant pleiotropic effects of Ay are caused by ectopic activation of a signaling pathway similar to that used during normal hair growth.

Agouti Signaling Protein↗
PubMed2003

A sensitive method for detecting variation in copy numbers of duplicated genes.

Gene duplications are common in the vertebrate genome, and duplicated loci often show a variation in copy number that may have important phenotypic effects. Here we describe a powerful method for quantification of duplicated copies based on pyrosequencing. A reliable quantification was obtained by amplification of the duplication break-point and a corresponding nonduplicated sequence in a competitive PCR assay. A comparison with an independent method for quantification based on the Invader technology revealed an excellent correlation between the two methods. The pyrosequencing-based method was evaluated by analyzing variation in copy number at the duplicated KIT/Dominant white locus in pigs. We were able to distinguish haplotypes at this locus by combining the duplication breakpoint test with a diagnostic test for a functionally important splice mutation in the duplicated gene. An extensive allelic variation, including the presence of a new allele carrying a single KIT copy expected to encode a truncated KIT receptor, was revealed when analyzing white pigs from commercial lines.

Algorithms↗
PubMed1995

Quantitative trait loci that modify the severity of spotting in piebald mice.

Mice homozygous for the recessive mutation piebald (s) exhibit a white-spotted coat caused by the defective development of neural crest-derived melanocytes. The severity of white spotting varies greatly, depending on the genetic background on which s is expressed. A backcross between two inbred strains of s/s mice that exhibit large differences in the degree of spotting was used to identify six genetic modifiers of piebald spotting on chromosomes 2, 5, 7, 8, 10, and 13. The loci differed in their spatial contribution to spotting on the dorsal versus ventral surfaces of mice; nonadditive interactions were observed between loci on chromosomes 2 and 5. This study underscores the power of using genetic analyses to identify and analyze loci involved in modifying the severity of phenotypic traits in mice.

Animals↗
PubMed1998

Molecular basis for the dominant white phenotype in the domestic pig.

The change of phenotypic traits in domestic animals and crops as a response to selective breeding mimics the much slower evolutionary change in natural populations. Here, we describe that the dominant white phenotype in domestic pigs is caused by two mutations in the KIT gene encoding the mast/stem cell growth factor receptor (MGF), one gene duplication associated with a partially dominant phenotype and a splice mutation in one of the copies leading to the fully dominant allele. The splice mutation is a G to A substitution in the first nucleotide of intron 17 and leads to skipping of exon 17. The duplication is most likely a regulatory mutation affecting KIT expression, whereas the splice mutation is expected to cause a receptor with impaired or absent tyrosine kinase activity. Immunocytochemistry showed that this variant form is expressed in 17- to 19-day-old pig embryos. Hundreds of millions of white pigs around the world are assumed to be heterozygous or homozygous for the two mutations. [The EMBL accession numbers for porcine KIT1*0101, KIT1*0202, KIT2*0202, and KIT2*0101 are AJ223228-AJ223231, respectively.]

Alternative Splicing↗
PubMed1997

Transgenic mice expressing IFN-gamma in the epidermis have eczema, hair hypopigmentation, and hair loss.

To study the role of IFN-gamma in the pathogenesis of inflammatory skin diseases, we used the involucrin promoter to overexpress IFN-gamma in the suprabasal layers of transgenic mouse epidermis. IFN-gamma mRNA and protein were readily detectable in the skin but not in the blood. Mice exhibited striking hypopigmentation of the hair due to a reduced abundance of DOPA-positive melanocytes. Severely affected mice had reddened skin, growth retardation, hair loss, and flaky skin lesions. Keratinocyte proliferation was increased, and there was epidermal thickening with spongiosis and parakeratosis. Suprabasal beta1 integrin expression and induction of keratin 17 in interfollicular epidermis provided evidence of perturbed differentiation. IFN-gamma receptor expression was reduced, and there was induction of ICAM-1 and MHC class II molecules on the surface of transgenic keratinocytes. The skin of severely affected mice was characterized by a dermal infiltrate of T lymphocytes and macrophages/monocytes, but the epidermis was almost devoid of Langerhans cells and T lymphocytes. The number of Langerhans cells in the lymph nodes was increased in the transgenics, and autoantibodies to keratinocytes were produced. Transgenic mice showed an increased contact hypersensitivity reaction to topical application of DNFB. We conclude that constitutive IFN-gamma expression in the epidermis results in a form of eczema resembling contact dermatitis and in a profound contact hypersensitivity reaction.

Animals↗
PubMed1995

Effects of monoclonal anti-c-kit antibody (ACK2) on melanocytes in newborn mice.

Previous studies indicate that c-Kit is required for postnatal melanocyte development. To understand the precise mechanisms of c-Kit dependence, we studied melanocyte development in newborn C57BL/6 mice by means of peritoneal injection of a monoclonal anti-c-Kit antibody (ACK2), which blocks c-Kit functions. The mice were injected once or more with ACK2 at various intervals after birth. In experiment 1, skin samples were examined on day 10 post-partum and in experiment 2 they were examined daily until day 10 post-partum. We studied melanocytes in the hair follicles, epidermis, and dermis by light and electron microscopy with dopa reactions and immunohistochemistry. Epidermal melanocytes in untreated mice were dopa negative and c-Kit positive on day 0 post-partum but became dopa positive soon thereafter. In ACK2-treated mice, the earlier the mice received ACK2 injections after birth, the fewer melanocytes they had, not only in the epidermis, but also in follicles. In these mice, melanocytes that had undergone apoptosis in the dermis and the follicles were detected ultrastructurally. Some appeared to have produced tyrosinase, because they had dopa-positive melanosomes. These results suggest that melanocytes in newborn mice are c-Kit dependent and undergo apoptosis when c-Kit receptors are blocked by ACK2 in the early days after birth. During this c-Kit-dependent period, melanocytes differentiate from dopa negative to positive and migrate from the epidermis to hair follicles.

Animals↗