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'Cyclic alopecia' in Msx2 mutants: defects in hair cycling and hair shaft differentiation.

Msx2-deficient mice exhibit progressive hair loss, starting at P14 and followed by successive cycles of wavelike regrowth and loss. During the hair cycle, Msx2 deficiency shortens anagen phase, but prolongs catagen and telogen. Msx2-deficient hair shafts are structurally abnormal. Molecular analyses suggest a Bmp4/Bmp2/Msx2/Foxn1 acidic hair keratin pathway is involved. These structurally abnormal hairs are easily dislodged in catagen implying a precocious exogen. Deficiency in Msx2 helps to reveal the distinctive skin domains on the same mouse. Each domain cycles asynchronously - although hairs within each skin domain cycle in synchronized waves. Thus, the combinatorial defects in hair cycling and differentiation, together with concealed skin domains, account for the cyclic alopecia phenotype.

Alopecia↗

Torsional method for evaluating hair damage and performance of hair care ingredients.

In this study, we have developed a single hair fiber torsional pendulum method to determine the role of the cuticle and the cortex on torsional properties with respect to fiber cross-sectional area, fiber rigidity, and energy dissipation at 65% RH and in the wet state. Our results demonstrate that in fine diameter fibers with a high cuticle-to-cortex ratio, the cuticula exert a significant effect on the torsional deformation behavior of hair fibers at both normal humidities and in the wet condition. In addition, our data indicate that energy dissipation is confined to fibers with a high cuticle-to-cortex ratio, and the amount of energy dissipated becomes more pronounced with increasing water content. The torsional properties of hair spray-treated fibers suggest that the deposited hair spray film masks the properties of the base fiber and imparts its own dissipative character to the measurement. Since tensile mechanical properties are often used to make claims about the performance of hair care products, we have compared the results obtained from torsional and tensile measurements on over-processed bleached hair fibers conditioned with Polyquaternium-10 and cetyl trimethylammonium bromide (CETAB) to evaluate which method is more advantageous. Our data demonstrate that torsional measurements can distinguish hair care products which reinforce the cuticle from those which affect the cortex, while tensile measurements showed no significant differences.

Biomechanical Phenomena↗

Loose anagen hair syndrome mimicking the uncombable hair syndrome.

A 7-year-old female presented with messy, difficult to manage scalp hair and mild, diffuse alopecia. Hair pull specimens, diagnostic for loose anagen hair syndrome, also showed hair shaft abnormalities described in the uncombable hair syndrome. We suggest that dysmorphic hair shafts observed on our patient account for her clinically unmanageable hair. Pertinent clinical, pathologic, and diagnostic features of both syndromes are reviewed.

Alopecia↗

Hair analysis for drugs of abuse. V. The facility in incorporation of cocaine into hair over its major metabolites, benzoylecgonine and ecgonine methyl ester.

We studied the incorporation of cocaine (COC), benzoylecgonine (BE) and ecgonine methyl ester (EME) into hair from blood. At first, the time courses of three drugs in rat plasma following i.p. administration of cocaine were investigated over 360 min. AUCs of COC, BE and EME in plasma were 14.2, 60.7 and 53.4 micrograms/ml/min, respectively. In contrast, the concentrations of the three compounds in hair were 16.4, 1.7 and 0.8 ng/mg. In spite of that, the AUC of COC in plasma was much lower than that of the other two compounds in plasma, the concentration of COC in hair was much higher than that of the other two compounds. The incorporation of COC into hair was much greater than that of BE and EME. If the incorporation of drugs from blood into hair is compared by [concentration in hair]/[AUC in plasma], that of COC, BE and EME is represented by 77:1.9:1. Our results suggest that the incorporation of drugs into hair from blood unexpectedly depends upon the physical properties of each drug.

Animals↗

Suppression of hair follicle development inhibits induction of sonic hedgehog, patched, and patched-2 in hair germs in mice.

Embryonic induction of hair follicles is a fascinating model of localized morphogenesis from a simple homogeneous epithelial cell sheet. Accumulating evidence indicates that Sonic hedgehog (Shh) signaling plays a central role in hair follicle formation. We quantitated the expression levels of Shh and its receptor genes, Patched (Ptc) and Patched-2 (Ptch2), in two distinct experimental systems in which the development of hair follicles was suppressed. Shh, Ptc, and Ptch2 were induced about six- to tenfold in normal embryonic hair germs in vivo as well as in developing skin tissue maintained in organ culture. This induction was almost completely inhibited both in the developing skin tissue of ICR mice cultured with 30ng/ml epidermal growth factor and in embryos of Tabby mutant mice (a model of hypohidrotic ectodermal dysplasia) at 14.5-15.5 days postcoitus. Expression of Shh, Ptc and Ptch2 was induced in the Tabby embryos at 16.5 days postcoitus, indicating that Shh signaling may be involved in the formation not only of the well-studied guard hair but also of the awl hair. The potential of the two biological systems for studying molecular mechanisms in hair follicle formation, particularly at an early phase including Shh signaling, is discussed.

Animals↗

Concentrations of some trace elements in hair, liver and kidney from autopsy subjects--relationship between hair and internal organs.

Autopsy samples of hair, liver and kidney cortex from 30 Swedish subjects (Caucasian) were analysed for Ag, Co, Cr, Hg, Sb, Se and Zn by neutron activation analysis (NAA). The following elements were observed to have higher concentrations in hair than in liver and kidney cortex: Ag, (Co), Cr and Hg (on a dry weight basis). Selenium was highly concentrated in kidney cortex, and Fe in liver. The observed concentrations of most of the elements were very variable for each tissue. In particular, Co values for hair showed more than a 5000-fold difference. However, Se values for hair were relatively constant. A highly significant positive correlation was observed between Hg concentrations in hair and kidney cortex. Somewhat weaker correlations were found between Hg in kidney cortex and liver and Se in hair and kidney cortex. The concentration of Co in liver correlated with that in kidney cortex. It was concluded that, with the exception of mercury, and to a lesser degree selenium, hair analysis did not provide a useful measure of the trace element status of the subjects included in this study.

Autopsy↗

Radioimmunoassay of drugs of abuse in hair. Part 1: Methadone in human hair, method adaptation and the evaluation of decontamination procedures.

A method suitable for the determination of methadone in human hair is presented. Adaptation and evaluation of a solid-phase I125 radioimmunoassay, designed for the quantitative measurement of methadone in urine, and development of a pre-analytical wash procedure has enabled a specific, sensitive and accurate analytical procedure to be developed. The specificity of the antiserum towards other drugs or biologically active compounds is evaluated up to a concentration of 100,000 ng ml-1 and accuracy covering a range of 0-450 ng ml-1 is found to be within 6% of expected methadone concentrations prepared in both drug free hair extract and urine. Inter-assay relative standard deviation (RSD) at concentrations of 5.1, 76.0 and 247 ng ml-1 methadone are 5.5, 2.5 and 3.6% respectively (n = 10) and intra-assay RSD at concentrations 2.3, 25.2 and 217 ng ml-1 are 5.3, 3.6 and 6.8% (n = 5). The limit of detection is 0.5 ng ml-1. Extraction of control drug free hair samples spiked with methadone at concentrations of 100, 250 and 400 ng ml-1 achieved recoveries of 86, 80 and 89%, respectively. Control hair samples contaminated with methadone are examined under differing wash procedures to assess their effectiveness in the removal of methadone contaminant. A suitable pre-analytical wash regime is proposed for removal of contaminant derived from external or environmental sources. The mechanics of the wash action and contaminant application to the hair is discussed. It is concluded that the adapted radioimmunoassay and developed pre-analytical decontamination procedure is a suitable technique to employ for the measurement of methadone in human hair, be it prescribed or abused, with concentrations expressed as ng methadone per mg hair.

Decontamination↗

Hair analysis for drugs of abuse XXI. Effect of para-substituents on benzene ring of methamphetamine on drug incorporation into rat hair.

In order to study the effect of para-substituents on the benzene ring of methamphetamine on drug incorporation into hair from blood, the plasma AUCs and hair concentrations of 7 methamphetamines [methamphetamine(MA), p-hydroxymethamphetamine(OHMA), p-bromomethamphetamine (BMA), p-aminomethamphetamine (AMA), p-nitromethamphetamine (NMA), p-methoxymethamphetamine (MOMA) and 3,4-methylenedioxymethamphetamine (MDMA)] plus propylhexedrine(PHX) in DA rats was determined after intraperitoneal injection at 5 mg/kg, with single dose for the plasma AUC and 10 doses for the hair concentration. Drug incorporation rates into hair (ICRs) were calculated by dividing each hair concentration by each plasma AUC. Comparing the highest value (NMA) to the lowest one (OHMA), the ICR of NMA was 31.7 times larger than that of OHMA. Using the ICR of MA which has no substitute on the benzene ring as a base point, nitro, bromo, methylenedioxy, methoxy and amino groups raised the drug incorporation into rat hair in this order. On the other hand, hydroxy substitution showed a negative effect on the ICR. In comparison between the ICRs of MA and PHX, it was found that the benzene ring shows higher affinity to melanin and less lipophilicity than the cyclohexyl ring. Our results showed that there is a relatively strong effect of the functional groups on drug incorporation into hair. The combination of melanin affinity and lipophilicity are clearly correlated with their ICR.

Animals↗

Hair dye-sensitized hairdressers: the cross-reaction pattern with new generation hair dyes.

Hair dye allergies are a frequent cause of occupational skin disease among hairdressers. Conventional hair dyes contain 4-phenylenediamine (PPD), 2, 5-diaminotoluene sulfate (DTS) and 2-nitro-4-phenylenediamine (ONPPD) as allergens. In new generation hair dyes, FD & C and D & C dyes are used in the hair dye formulations. This study investigated the cross-reaction pattern of new generation hair dyes among hairdressers (n = 40) with a known allergy to PPD and/or DTS and/or ONPPD. In the 40 hairdressers no positive reactions were observed to the single FD & C and D & C dyes. In two hairdressers, doubtful reactions were observed to one or more of the hair dye formulations. The data from this study suggest that for hairdressers sensitized to PPD and/or DTS and/or ONPPD this new generation of hair dyes is a safe alternative for use in their salons.

Allergens↗

Mutations in the hair cortex keratin hHb6 cause the inherited hair disease monilethrix.

Pathogenic mutations in a large number of human epithelial keratins have been well characterized. However, analogous mutations in the hard alpha-keratins of hair and nail have not yet been described. Monilethrix is a rare autosomal dominant hair defect with variable expression. Hairs from affected individuals show a beaded structure of alternating elliptical nodes and constrictions (internodes). These internodes exhibit a high prospensity to weathering and fracture. Strong evidence that trichocyte keratin defects might underlie this hair disorder was provided by genetic linkage analyses that mapped this disease to the type-II keratin gene cluster on 12q13. All affected individuals from a four-generation British family with monilethrix, previously linked to the type-II keratin gene cluster, as well as three unrelated single monilethrix patients, exhibited a heterozygous point mutation in the gene for type-II hair cortex keratin hHb6, leading to lysine substitution of a highly conserved glutamic acid residue in the helix termination motif (Glu 410 Lys). In a three-generation French family with monilethrix of a milder and variable phenotype, we detected another heterozygous point mutation in the same glutamic acid codon of hHb6, which resulted in a conservative aspartic acid substitution (Glu 410 Asp). These mutations provide the first direct evidence for involvement of hair keratins in hair disease.

Adolescent↗

Characterization of the proteins of guinea-pig hair and hair-follicle tissue.

This work forms a part of a study of the mechanism and control of protein synthesis in the hair follicle and concerns the characterization of the proteins of hair-follicle tissue and for comparative reasons those of the hair itself. 1. Five different groups of reduced carboxymethylated proteins were delineated from both tissues; these were: group 1A proteins, which appeared to be aggregates of the group 2 proteins; group 1B proteins, soluble at pH4.4, which were thought to originate from the medulla and inner-rootsheath layers; group 2 proteins, which were defined as the main low-sulphur keratin proteins insoluble at pH4.4; group 3 proteins, the precise origin of which is not known; and the group 4 proteins, which were defined as the main high-sulphur keratin proteins soluble at pH4.4. 2. With the single exception of the group 1B proteins, the types and properties of all hair and hair-follicle proteins were identical as far as could be determined by use of such criteria as multiplicity of components, molecular charge, molecular weight and amino acid composition. 3. Two significant quantitative differences were noted: in follicle extracts there were more group 2 proteins but less group 3 and group 4 proteins than in hair extracts; and secondly, in the follicle group 4 proteins, there were more proteins of lowest molecular weight and S-carboxymethylcysteine content, but fewer proteins of the highest molecular weight and S-carboxymethylcysteine conent than in the hair group 4 proteins. 4. These quantitative differences are discussed in terms of the mechanism of synthesis of the keratin proteins. 5. Follicle group 1B proteins are postulated to have arisen from the trichohyalin droplets of the developing medulla and inner-root-sheath layers of the follicle and may be precursors of the proteins of the mature medulla and inner root sheath.

Alkylation↗

Hair-cycle-associated remodeling of the peptidergic innervation of murine skin, and hair growth modulation by neuropeptides.

As the neuropeptide substance P can manipulate murine hair growth in vivo, we here further studied the role of sensory neuropeptides in hair follicle biology by determining the distribution and hair-cycle-dependent remodeling of the sensory innervation in C57BL/6 mouse back skin. Calcitonin-gene-related peptide, substance P, and peptide histidine methionine (employed as vasoactive intestinal peptide marker) were identified by immunohistochemistry. All of these markers immunolocalized to bundles of nerve fibers and to single nerve fibers, with distinct distribution patterns and major hair-cycle-associated changes. In the epidermis and around the distal hair follicle and the arrector pili muscle, only calcitonin-gene-related peptide immunoreactive nerve fibers were visualized, whereas substance P and peptide histidine methionine immunoreactive nerve fibers were largely restricted to the dermis and subcutis. Compared to telogen skin, the number of calcitonin-gene-related peptide, substance P, and peptide histidine methionine immunoreactive single nerve fibers increased significantly (p < 0.01) during anagen, including around the bulge region (the seat of epithelial stem cells). Substance P significantly accelerated anagen progression in murine skin organ culture, whereas calcitonin-gene-related peptide and a substance-P-inhibitory peptide inhibited anagen (p < 0.05). The inhibitory effect of calcitonin-gene-related peptide could be antagonized by coadministrating substance P. In contrast to substance P, calcitonin-gene-related peptide failed to induce anagen when released from subcutaneous implants. This might reflect a differential functional assignment of the neuropeptides calcitonin-gene-related peptide and substance P in hair growth control, and invites the use of neuropeptide receptor agonists and antagonists as novel pharmacologic tools for therapeutic hair growth manipulation.

Animals↗

Fas and c-kit are involved in the control of hair follicle melanocyte apoptosis and migration in chemotherapy-induced hair loss.

Chemotherapy alters the structure and function of hair follicle melanocytes. Molecular mechanisms controlling melanocyte responses during chemotherapy-induced hair loss, however, remain largely unknown. Using immunohistology and multicolor confocal microscopy, we show here that cyclophosphamide administration to C57BL/6 mice alters the activity and fate of hair follicle melanocytes. After 24-48 h, hair bulb melanocytes expressing Fas undergo apoptosis. The number of apoptotic follicular melanocytes is significantly reduced (p<0.01) in cyclophosphamide-treated Fas knockout mice compared to wild-type controls, suggesting that Fas signaling contributes to chemotherapy-induced melanocyte death. After 3-5 d, surviving hair bulb melanocytes express c-kit receptor, proliferate, and appear to migrate up the outer root sheath. Tyrosinase-positive and melanogenically active cells then appear in the epidermis. By Western blotting and immunohistochemistry, expression levels of the c-kit ligand, stem cell factor, in skin and epidermis are strongly increased after cyclophosphamide treatment. Cyclophosphamide-induced migration of the hair follicle melanocytes into epidermis is completely abrogated by administration of c-kit neutralizing antibody. These data suggest that chemotherapy induces a complex response in the hair follicle melanocytes, which includes apoptosis, proliferation, and migration. Pharmacologic manipulation of Fas and c-kit signaling pathways might be useful for the correction of skin hyperpigmentation as a side-effect of chemotherapy.

Alopecia↗

Laser hair removal: a review and report on the use of the long-pulsed alexandrite laser for hair reduction of the upper lip, leg, back, and bikini region.

BACKGROUND: The mechanism and permanence of laser-assisted hair removal remains a formidable task in the medical community. OBJECTIVE: The purpose of this study was to determine the safety and long-term efficacy of the long-pulsed or normal mode alexandrite infrared laser for hair depilation. METHODS: Beginning in October 1996, a total of 31 anatomic sites on 22 patients ranging in age from 25 to 59 years (mean 42 years) were evaluated to assess hair removal. Treatment sites included 17 upper lips, 9 legs, 2 backs, and 3 bikini regions. Eligible patients were of Fitzpatrick skin types I-III. Patients were treated using the long-pulsed alexandrite infrared laser at 755 nm, single-pulse technique, 10 mm spot size, 10% overlap, pulse durations of 5, 10, and 20 msec, and a fluence of 20 J/cm2. Subjective patient improvement and objective, blinded graded improvement was assessed at 1, 2, 3, and 6 months. RESULTS: Objective blinded grading at 6 months revealed that hair reduction varied both with the pulse duration and anatomic location. Maximum reductions observed were 40%, 56%, 50%, and 15% for the lip, leg, back, and bikini areas, respectively. Upper lip hair reduction increased from 40% to 54% at 6 months when a second treatment was performed 8 weeks after the initial treatment. CONCLUSION: The long-pulsed alexandrite laser is safe and effective in reducing hair growth. Treatment efficacy varies with the anatomic location, pulse duration, and number of treatments. A single-pulse technique utilizing a 10 msec pulse duration at 20 J/cm2 produced the greatest hair reduction. No permanent adverse effects occurred on skin types I-III at the parameters tested.

Adult↗

Evidence that the satin hair mutant gene Foxq1 is among multiple and functionally diverse regulatory targets for Hoxc13 during hair follicle differentiation.

It is increasingly evident that the molecular mechanisms underlying hair follicle differentiation and cycling recapitulate principles of embryonic patterning and organ regeneration. Here we used Hoxc13-overexpressing transgenic mice (also known as GC13 mice), known to develop severe hair growth defects and alopecia, as a tool for defining pathways of hair follicle differentiation. Gene array analysis performed with RNA from postnatal skin revealed differential expression of distinct subsets of genes specific for cells of the three major hair shaft compartments (cuticle, cortex, and medulla) and their precursors. This finding correlates well with the structural defects observed in each of these compartments and implicates Hoxc13 in diverse pathways of hair follicle differentiation. The group of medulla-specific genes was particularly intriguing because this included the developmentally regulated transcription factor-encoding gene Foxq1 that is altered in the medulladefective satin mouse hair mutant. We provide evidence that Foxq1 is a downstream target for Hoxc13 based on DNA binding studies as well as co-transfection and chromatin immunoprecipitation assays. Expression of additional medulla-specific genes down-regulated upon overexpression of Hoxc13 requires functional Foxq1 as their expression is ablated in hair follicles of satin mice. Combined, these results demonstrate that Hoxc13 and Foxq1 control medulla differentiation through a common regulatory pathway. The apparent regulatory interactions between members of the mammalian Hox and Fox gene families shown here may establish a paradigm for "cross-talk" between these two conserved regulatory gene families in different developmental contexts including embryonic patterning as well as organ development and renewal.

3T3 Cells↗

A study of mercury in the hair of dentists and dental-related professionals in 1985 and subcohort comparison of 1972 and 1985 mercury hair levels.

Dentists may be exposed to mercury used in dental restorations. An epidemiologic study was conducted in central New York in 1985 comparing the concentration of mercury in the hair of 85 dentists to that of 23 dental-related health professionals (mainly orthodontists and oral surgeons) who do not use mercury. Mercury in the hair of dentists was nominally higher (2.98 +/- 0.57 ppm, mean +/- SE) than that of the control group (1.84 +/- 0.20 ppm) but not significantly so. There was a significant positive linear trend in the concentration of mercury in the dentists' hair with the number of years they had been in practice. Those dentists who wore masks when removing old mercury containing fillings showed significantly (p = 0.03) lower mercury concentrations in hair (1.7 +/- 0.26 ppm, mean +/- SE) than those who did not (3.65 +/- 0.85 ppm). Mercury concentration in the hair of 23 of the above dentists analyzed in 1972 was 16.77 +/- 4.00 ppm (mean +/- SE), significantly higher (p = 0.008) than that of the same dentists in 1985 (5.27 +/- 1.85 ppm). The reduction is believed due to the currently used pre-prepared disposable or reusable capsules containing the amalgam versus formerly mixing the ingredients manually. This may also account for the lack of a significant difference in mercury in the hair of the dentists versus that of the control group in 1985. The statistical relationships between mercury concentrations in hair of the two groups and reported health effects, as well as other factors including fish consumption, number of restorations per day, office floor covering, and urban or rural domicile, are discussed.

Adult↗

The actin filament content of hair cells of the bird cochlea is nearly constant even though the length, width, and number of stereocilia vary depending on the hair cell location.

By direct counts off scanning electron micrographs, we determined the number of stereocilia per hair cell of the chicken cochlea as a function of the position of the hair cell on the cochlea. Micrographs of thin cross sections of stereociliary bundles located at known positions on the cochlea were enlarged and the total number of actin filaments per stereocilium was counted and recorded. By comparing the counts of filament number with measurements of actin filament bundle width of the same stereocilium, we were able to relate actin filament bundle width to filament number with an error margin (r2) of 16%. Combining this data with data already published or in the process of publication from our laboratory on the length and width of stereocilia, we were able to calculate the total length of actin filaments present in stereociliary bundles of hair cells located at a variety of positions on the cochlea. We found that stereociliary bundles of hair cells contain 80,000-98,000 micron of actin filament, i.e., the concentration of actin is constant in all hair cells with a range of values that is less than our error in measurement and/or biological variation, the greatest variation being in relating the diameters of the stereocilia to filament number. We also calculated the membrane surface needed to cover the stereocilia of hair cells located throughout the cochlea. The values (172-192 micron 2) are also constant. The implications of our observation that the total amount of actin is constant even though the length, width, and number of stereocilia per hair cell vary are discussed.

Actins↗

Detection of LSD and metabolite in rat hair and human hair.

To examine the feasibility of detecting lysergic acid diethylamide (LSD) and its metabolites in hair, LSD was administered to rats with pigmented hair at 0.05, 0.1, 0.5, 1, and 2 mg/kg intraperitoneally once per day for 10 successive days. The rats were shaved just before the first administration, and newly grown hair was collected 4 weeks later. After being washed with 0.1% sodium dodecyl sulfonate and water and being dried in a desiccator, each 20-mg hair sample was extracted with 2 mliter methanol-5N HCl (20:1) under ultrasonication for 1 h and stored at room temperature for 14 h. The extract was evaporated to dryness, extracted from 0.1M NaOH with dichloromethane, and derivatized with a mixture of trimethylsilylimidazole, bis-(trimethylsilyl)acetamide, and trimethylchlorosilane (3:3:2, v/v/v) for gas chromatographic-mass spectrometric (GC-MS) analysis using LSD-d10 or lysergic acid methylpropylamide (LAMPA) as the internal standard. Selected ions were monitored at m/z 395, 293, and 279 for TMS-LSD and at m/z 381, 279, and 254 for the trimethylsilyl derivative of N-demethyl-LSD (TMS-norLSD). LSD and norLSD were also detected by high-performance liquid chromatography (HPLC) with fluorometric detection (excitation, 315 nm; emission, 420 nm). LSD was detected in the rat hair following the lowest dose (0.05 mg/kg), whereas norLSD was only detectable in the hair following the highest dose (2 mg/kg). The same GC-MS and HPLC assays were applied to the analysis of hair from 17 self-reported LSD users, and LSD was detected in two of the samples.

Adolescent↗