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Rapid, active hair bundle movements in hair cells from the bullfrog's sacculus.

Hair bundles, the mechanically sensitive organelles of hair cells in the auditory and vestibular systems, are elastic structures that are deflected by sound or acceleration. To examine rapid mechanical events associated with mechanoelectrical transduction, we stimulated individual hair bundles with flexible glass fibers and measured their responses with a temporal resolution of 400 microsec. When a hair bundle from the bullfrog's sacculus was abruptly deflected in the positive direction, the bundle's motion in the direction of stimulation was interrupted within the initial few milliseconds by an active movement, or twitch. This response was biphasic, with an initial component in the direction of the stimulus and a second component in the opposite direction. The amplitude and duration of the twitch depended on the bundle's initial position and the size and rise time of the stimulus; the twitch was largest over the range of bundle deflections in which transduction was most sensitive. Under displacement clamp conditions, in which a hair bundle's position was changed and then held constant with negative feedback, the twitch manifested itself as a biphasic force exerted by the bundle. Some hair bundles produced twitches in response to negatively directed stimuli, exhibited stimulus-evoked damped oscillations, or twitched spontaneously. The hair bundle's ability to perform work against an external load and to oscillate in response to stimulation indicates that the bundle could supply feedback for mechanical amplification in vertebrate auditory organs.

Animals↗

Sparse and wavy hair: a new model for hypoplasia of hair follicle and mammary glands on rat chromosome 17.

Mutant animals in the skin and hair have been used to identify important genes in biomedical research. We describe a new mutant rat, sparse and wavy hair (swh), that spontaneously arose in a colony of inbred WTC rats. The mutant phenotype was characterized by sparse and wavy hair, which was most prominent at age 3-4 weeks, and was inherited in an autosomal recessive manner. The swh/swh rats showed impaired gain of body weight, and their hair follicles were reduced both in number and size, associated with hypoplasia of the sebaceous glands and the subcutaneous fat tissue. Female swh/swh rats were unable to suckle their offspring. Their mammary glands were hypoplastic, and differentiation of mammary epithelial and myoepithelial cells was impaired. Linkage analysis of 579 backcross rats localized the swh locus to a .35-cM region between D17Rat131 and D17Rat50 in the distal end of rat Chr 17. The swh locus spanned the 3.7-Mb genomic region where 24 genes have been mapped and corresponded to the centromere region of the mouse Chr 2 or the region of the human Chr 10p11.1-p14. None of the genes or loci described in mouse or human hair and skin diseases mapped to these regions. These findings suggest that the rat swh is a novel mutation associated with impaired development of the skin appendages, such as hair follicles, sebaceous glands, and mammary glands, and will provide an experimental model to clarify a gene and mechanisms for development of skin appendages.

Animals↗

Pili trianguli et canaliculi: a distinctive hair shaft defect leading to uncombable hair.

Uncombable hair syndrome refers to a clinical disorder characterized by scalp hairs arranged in bundles in all directions that resist to brush and comb. Several entities may lead to spun-glass hair. As a rule the syndrome becomes obvious during the first years of life. The hair is normal in quantity, and increased fragility is not a common feature. The hair is often dry with silvery blond color. Under the light microscope the hairs may appear normal. Scanning electron microscopy shows a characteristic triangular, kidney- or heat-shaped diameter with typical longitudinal canalicular deformation. We present a 9-year-old girl with the typical clinical features of pili trianguli et canaliculi. Investigation by scanning electron microscopy confirmed the diagnosis. In addition the girl had enamel defects of the teeth and nail abnormalities that classify for a subtype of ectodermal dysplasia.

Child↗

Activation of the Notch pathway in the hair cortex leads to aberrant differentiation of the adjacent hair-shaft layers.

Little is known about the mechanisms underlying the generation of various cell types in the hair follicle. To investigate the role of the Notch pathway in this process, transgenic mice were generated in which an active form of Notch1 (Notch(DeltaE)) was overexpressed under the control of the mouse hair keratin A1 (MHKA1) promoter. MHKA-Notch(DeltaE) is expressed only in one precursor cell type of the hair follicle, the cortex. Transgenic mice could be easily identified by the phenotypes of curly whiskers and wavy, sheen pelage hair. No effects of activated Notch on proliferation were detected in hair follicles of the transgenic mice. We find that activating Notch signaling in the cortex caused abnormal differentiation of the medulla and the cuticle, two neighboring cell types that did not express activated Notch. We demonstrate that these non-autonomous effects are likely caused by cell-cell interactions between keratinocytes within the hair follicle and that Notch may function in such interactions either by directing the differentiation of follicular cells or assisting cells in interpreting a gradient emanating from the dermal papilla.

Animals↗

Doxorubicin-induced hair loss in the Angora rabbit: a study of treatments to protect against the hair loss.

An animal model for anticancer drug-induced hair loss has been developed using the Angora rabbit given i.v. doxorubicin, 2 mg/kg, twice weekly for 3 weeks. There was a 167% increase in the weight of hair collected by grooming between weeks 2 and 5, and a 72% inhibition of new hair growth at week 6 compared with non-treated animals. The hairs that grew in the doxorubicin treated rabbits did so at the same rate as in non-treated rabbits and appeared normal by light microscopy. Topical application of dimethylsulfoxide (DMSO), of 10% alpha-tocopherol in DMSO, of 0.5% naphthazoline hydrochloride in DMSO, of 0.1% fluocinolone acetonide in a propylene glycol base and local hypothermia did not provide any protection against doxorubicin-induced hair loss. Angora rabbits fed an alpha-tocopherol-deficient diet for 6 weeks showed decreased hair growth compared with animals fed a normal diet or a diet supplemented with 100 mg alpha-tocopherol acetate twice a week for 6 weeks. Some rabbits fed the alpha-tocopherol-deficient diet died when given doxorubicin. Rabbits fed the alpha-tocopherol-supplemented diet showed evidence of protection against doxorubicin-dependent inhibition of new hair growth.

Alopecia↗

Judicial applications of hair testing for addicts in Crete: sectional hair analysis of heavy heroin abusers.

Laboratory examination of hair from drug users has been employed for the last 5 years in Crete, in addition to the psychiatric or other forensic clinical examinations necessary for the confirmation of a person's use of drugs. The present study reports results of total and sectional head, axillary and pubic hair analysis of imprisoned abusers under interrogation and awaiting presentation at the Crime Court. Morphine levels in total head hair samples 1, 2 and 4 months after preliminary imprisonment ranged from 1.2 to 38.2, 0.5 to 22.5 and 0.1 to 4.9 ng/mg of hair respectively, while the maximum morphine levels amongst all studied groups of those arrested were found in the sections of axillary and pubic hair. Notably high morphine levels in head, axillary and pubic hair sections (13.7, 8.4 and 18.1) ng/mg respectively) were measured, even in abusers who had been imprisoned between 2 and 4 months. Hair tests may considerably assist to evaluate the systematic present and past abuse of heroin and other drugs. Consequently, it may be used as valuable expertise evidence during questioning and in court.

Journal Article↗

A nonsymbiotic root hair tip growth phenotype in NORK-mutated legumes: implications for nodulation factor-induced signaling and formation of a multifaceted root hair pocket for bacteria.

The Medicago truncatula Does not Make Infections (DMI2) mutant is mutated in the nodulation receptor-like kinase, NORK. Here, we report that NORK-mutated legumes of three species show an enhanced touch response to experimental handling, which results in a nonsymbiotic root hair phenotype. When care is taken not to induce this response, DMI2 root hairs respond morphologically like the wild type to nodulation factor (NF). Global NF application results in root hair deformation, and NF spot application induces root hair reorientation or branching, depending on the position of application. In the presence of Sinorhizobium meliloti, DMI2 root hairs make two-dimensional 180 degrees curls but do not entrap bacteria in a three-dimensional pocket because curling stops when the root hair tip touches its own shank. Because DMI2 does not express the promoter of M. truncatula Early Nodulin11 (ENOD11) coupled to beta-glucuronidase upon NF application, we propose a split in NF-induced signaling, with one branch to root hair curling and the other to ENOD11 expression.

Genes, Plant↗

Evaluation of a new X-ray fluorescent analysis technique for the creation of a Nordic hair database: elemental distributions within the root and the virgin segment of hair fibers.

A new, non-destructive X-ray fluorescence technique for quantitative estimation of elemental content in biological tissues has been developed. Technical and instrumental characteristics of the ITRAX X-ray spectrometer have been evaluated in relation to the properties of biological samples, i.e., human hair fibers. Thus, attenuation variations of the fluorescent X-rays in the hair bulk mass were demonstrated by analysis of sulfur, calcium, and zinc in a virgin part near the root of one hair fiber with elliptical cross section. By rotation of the hair fiber and successive analyses made of the same part of the hair fiber, the results showed that concentrations of elements varied as functions of the diameter of the analyzed hair volume. Other sources of errors are also discussed. The ITRAX instrument allows for precise, fast, non-destructive, simultaneous, quantitative recording of the detected elements and trace elements down to levels of 1 ppm (microg/g). It was used for assessment of normal values of physiologically important elements present in hair in a cohort of normal, healthy Swedish, Caucasian individuals. The database constructed from data retrieved from a conceivably homogeneous ethnic set of individuals represents, to our knowledge, the first of its kind.

Evaluation Studies as Topic↗

Hair cycle-dependent plasticity of skin and hair follicle innervation in normal murine skin.

The innervation of normal, mature mammalian skin is widely thought to be constant. However, the extensive skin remodeling accompanying the transformation of hair follicles from resting stage through growth and regression back to resting (telogen-anagen-catagen-telogen) may also be associated with alteration of skin innervation. We, therefore, have investigated the innervation of the back skin of adolescent C57BL/6 mice at various stages of the depilation-induced hair cycle. By using antisera against neuronal (protein gene product 9.5 [PGP 9.5], neurofilament 150) and Schwann cell (S-100, myelin basic protein) markers, as well as against neural cell adhesion molecule (NCAM) and growth-associated protein-43 (GAP-43), we found a dramatic increase of single fibers within the dermis and subcutis during early anagen. This was paralleled by an increase in the number of anastomoses between the cutaneous nerve plexuses and by distinct changes in the nerve fiber supply of anagen vs. telogen hair follicles. The follicular isthmus, including the bulge, the seat of epithelial follicle stem cells, was found to be the most densely innervated skin area. Here, a defined subpopulation of nerve fibers increased in number during anagen and declined during catagen, accompanied by dynamic alterations in the expression of NCAM and GAP-43. Thus, our study provides evidence for a surprising degree of plasticity of murine skin innervation. Because hair cycle-associated tissue remodeling evidently is associated with tightly regulated sprouting and regression of nerve fibers, hair cycle-dependent alterations in murine skin and hair follicle innervation offer an intriguing model for studying the controlled rearrangement of neuronal networks in peripheral tissues under physiological conditions.

Animals↗

Hair analysis for nicotine and cotinine: evaluation of extraction procedures, hair treatments, and development of reference material.

Analysis of nicotine and cotinine in human hair can provide information on nicotine intake and exposure to environmental tobacco smoke over a long period of time. Nonetheless, to better assess the usefulness of hair analysis to determine smoking habits or exposures, all procedures have to be standardized. Various solvents were tested as washing solvents to eliminate external contamination from nicotine. Dichloromethane was found effective when used for two washes prior to the extraction. Basic and acid digestion of hair followed by solid phase extraction with Extrelut-3 glass column using dichloromethane:isopropyl alcohol (9:1) as eluting mixture both gave good recoveries of nicotine and cotinine, when compared with extractions reported in the literature. The extraction method was free from substances, which could interfere in the chromatographic analysis. Furthermore, the addition of methanolic HCl to the eluting mixture prevented the loss of nicotine during the evaporation step before chromatography. Chromatography was performed using a reversed-phase column and a U.V. detection at 254 nm. Furthermore, hair treatments (dyes, permanent wave, hydrogen peroxide) caused a major decrease in the nicotine content in hair, and a smaller effect on cotinine levels. However, the effect of various treatments was not reproducible. Several attempts to produce reference materials were carried out. Nicotine and cotinine standard solutions at different concentrations were added to blank hair soaked in dimethylsulfoxide, methanol and water.

Chromatography, High Pressure Liquid↗

The influence of hair color on the concentration of zinc and copper in boys' hair.

Head hair of 150 normal boys from Brazil ranging in age from 1 to 12 years was studied for the influence of color on concentrations of zinc and copper. Hair color was classified visually and also quantified by melanin concentration. Visual classification and spectrophotometric measurements of melanin showed good agreement for blond and black colors, whereas large discrepancies were observed for intermediate colors such as light and dark brown. Hair distributed in four ranges of melanin concentration (the numerical estimate of color) showed no significant differences for concentration of Zn and Cu but showed a significantly higher (P less than 0.01) concentration for Zn:Cu in black hair than in the other color groups. Correlation between mineral content (Zn and Cu) and melanin was low and nonsignificant except for Zn in hair color ranging from 0-100 melanin units (r = -0.34, P less than 0.05). Discussion of these findings is presented regarding the importance of hair color change in children and estimation of mineral nutritional status.

Brazil↗

Thymosin beta4 increases hair growth by activation of hair follicle stem cells.

Thymosin beta4, a 43-amino acid polypeptide that is an important mediator of cell migration and differentiation, also promotes angiogenesis and wound healing. Here, we report that thymosin beta4 stimulates hair growth in normal rats and mice. A specific subset of hair follicular keratinocytes in mouse skin expresses thymosin beta4 in a highly coordinated manner during the hair growth cycle. These keratinocytes originate in the hair follicle bulge region, a niche for skin stem cells. Rat vibrissa follicle clonogenic keratinocytes, closely related, if not identical, to the bulge-residing stem cells, were isolated and their migration and differentiation increased in the presence of nanomolar concentrations of thymosin beta4. Expression and secretion of the extracellular matrix-degrading enzyme matrix metalloproteinase-2 were increased by thymosin beta4. Thus, thymosin beta4 accelerates hair growth, in part, due to its effect on critical events in the active phase of the hair follicle cycle, including promoting the migration of stem cells and their immediate progeny to the base of the follicle, differentiation, and extracellular matrix remodeling.

Animals↗

Equine alopecia areata autoantibodies target multiple hair follicle antigens and may alter hair growth. A preliminary study.

Several cases of an alopecia areata (AA)-like disease have been reported in mammalian species. How similar this disorder(s) is to human AA is unclear. We have previously shown that human AA is associated with antibodies to hair follicle (HF)-specific antigens and that similar antibody reactivities also occur in the C3H/HeJ "AA" murine model and in dogs with spontaneously occurring AA. The current preliminary study was conducted to determine whether a horse with AA-like hair loss contained circulating antibodies to HE The pathogenic potential of these antibodies was examined by passive transfer into anagen skin of C57BL/ 10 black mice. Indirect immunofluorescence analysis indicated that the equine "AA" serum reacted intensely with the inner root sheath, outer root sheath and pre-cortex of equine HF Immunoblot examination revealed antibodies to a 200-220 kDa doublet and to antigens of 40-60 kDa. Notably, this serum, but not control serum, contained antibodies that selectively immunoprecipitated trichohyalin from HF protein extracts. IgG fractions of serum obtained from an "AA" horse and from a normal control horse were injected into anagen murine skin. Histologically, normal hair regrowth was observed in mice injected with normal equine IgG. By contrast, hair did not re-grow in an area around the injection site of AA-treated mice even 13 weeks after first injection. This skin contained telogen follicles, most often without associated shafts, despite the presence of anagen HF in the remaining dorsum skin. While this study is preliminary, it demonstrates for the first time that antibodies to HF antigens are a feature of AA-like hair loss in horses. Some reactivities (e.g. against trichohyalin) were similar to those previously observed in "AA" dogs. Further, we provide in this pilot study preliminary evidence that such antibodies may disrupt hair re-growth when passively transferred into mice, supporting the view that anti-HF antibodies in AA may have pathogenic potential.

Alopecia↗

[Pili canaliculi (uncombable hair syndrome or spun glass hair syndrome). A scanning electron microscope study of ten new cases (author's transl)].

"Uncombable hair" is the denomination applied to a new abnormality of the hair, being characterized by its arranged in bundles disposed in different directions and which are irreductible on combing. It may have a familial trait and starts at the age of 3 months onwards. It appears in children of both sexes, whose hair becomes dry, tightly curled, shiny, lighter and impossible to comb. There are no accompanying abnormalities in the development. Neither have any biological changes been registered. The clinical and ultrastructural aspects of 10 cases of children affected with "uncombable hair" are presented. At the scanning electron microscope we have observed longitudinally disposed canalicular formations on the cuticular surface of 50 p. 100 of hair taken from each patient. The canal is, in some zones, more excavated than in others, occasionaly has an irregular outline and sometimes is uniformly located nearly along the whole length of the hair. The transversal section shows triangular aspects, kidney-shaped or completely irregular. We agree with Dupré to use the term pili canaliculi for the defect shown by these patients.

Adolescent↗

Ability to culture dermal papilla cells from red deer (Cervus elaphus) hair follicles with differing hormonal responses in vivo offers a new model for studying the control of hair follicle biology.

Red deer stags annually grow two distinct seasonal coats, a winter coat and a summer coat; in addition, they produce a mane during the breeding season when plasma testosterone levels are high, which is replaced by the short neck hairs of the summer coat when testosterone levels are low. As two very different hair types are produced from the same follicle under hormonal regulation, they offer an interesting model for studying the effects of hormones, particularly androgens, on mammalian hair growth. Since the dermal papilla of the hair follicle has a regulatory function and is probably the site of androgen action, we have investigated whether cells from the dermal papilla can be readily cultured from various types of red deer follicles; as the follicular connective tissue sheath may regenerate a new papilla in vivo, this was also examined. Individual dermal papillae and lower portions of the connective tissue sheath were microdissected from mane and flank follicles of red deer stags during the winter breeding season and from the summer coat during the nonbreeding season. Primary cultures were established from isolated dermal papillae, connective tissue sheath and dermal explants, subcultured and reestablished after freezing. Deer dermal papilla cells resembled sheep cells; they displayed a polygonal shape and irregular organisation, but did not form aggregates in contrast to human and rat vibrissa cells. Connective tissue sheath cell morphology was intermediate between that of dermal papilla cells and dermal fibroblasts. However, all three cell types derived during the breeding season grew at a much faster rate than the same cells derived during the nonbreeding season. Therefore, primary cell lines can be fairly readily derived from deer hair follicles. Since the red deer stag offers both androgen-dependent neck (mane) and control flank follicles in the breeding season, plus control nonbreeding season neck follicles, this means that stag follicular cells, particularly the dermal papilla cells, appear to offer a unique novel model system for the study of the hormonal regulation of hair growth.

Androgens↗

Distribution and specific central projections of mechanoreceptors in the thorax and proximal leg joints of locusts. II. The external mechanoreceptors: hair plates and tactile hairs.

Tactile hairs on the locust thorax can be divided into two classes by their external morphology and their central projection pattern: Short hairs, 10--100 micrometer in length, which are assembled in distinct plates and rows, and long hairs, 100--800 micrometer in length, which are distributed all over the body and are organized in large fields or aligned along the ridges of the appendages. The sensory fibers of the first class arborize in the lateral dorsal neuropile of thoracic ganglia and then extend further into the ipsilateral half of the corresponding ganglion in three main bundles from which fine rami of fibers end in the intermediate neuropile. In all three thoracic ganglia the projection pattern of homologous hair plates is similar. The sensory fibers of the second class exclusively terminate in special median ventral neuropiles, the ventral association center (VAC) and ventralmost ventral association center (VVAC). In addition fibers from meso- and metathoracic hairs, located close to the longitudinal midline of the animal, may terminate in the contralateral VAC and with one branch project to the next anterior ganglion through the ipsilateral connective. In contrast, fibers from prothoracic hairs were not found to leave their ganglion.

Animals↗

Actin filaments, stereocilia, and hair cells of the bird cochlea. III. The development and differentiation of hair cells and stereocilia.

The cochleae of chick embryos of 8 days of incubation until hatching (21 days) were examined by scanning electron microscopy. Unlike what one would expect from the literature, the total number of hair cells per cochlea (10,405 +/- 529) is already determined and visible in a 10-day embryo and the growth of the cochlea is a result of the growth in size and surface area of the hair cells. We also find that the hair cells differentiate simultaneously throughout the cochlea and have followed the differentiation of individual hair cells throughout development. During development we find that the total number, hexagonal packing, and orientation of the stereocilia in each hair cell is determined early and accurately (9- to 10-day embryos). The stereocilia then begin to elongate in all the cells of the cochlea at approximately 0.5 micron/day. By Day 12 the tallest stereocilia in each cell are 1.5-1.8 micron long, the mature length for cells at the proximal end of the cochlea. At this point all stereocilia cease elongating, but those along the inferior edge gradually increase in width from 0.11 micron to maximally 0.19 micron in 17-day embryos. When the stereocilia on the inferior edge reach their mature width, widening ceases and the elongation of stereocilia in the distal hair cells begins again. When these stereocilia have attained their mature lengths, they stop growing. Thus elongation and widening of stereocilia are separated in time. During this period, 11 to 13 days, the shape of the tufts at the proximal end of the cochlea changes. This occurs because stereocilia in the front of each tuft are absorbed while others at the sides appear de novo. This rearrangement converts a circular bundle of stereocilia to a rectangular bundle.

Actins↗

Expression of hair-related keratins in a soft epithelium: subpopulations of human and mouse dorsal tongue keratinocytes express keratin markers for hair-, skin- and esophageal-types of differentiation.

The dorsal surfaces of mammalian tongues are covered with numerous projections known as filiform papillae whose morphology varies in different species. Using a panel of monoclonal antibodies to keratins as probes, we have established that, in both human and mouse, the interpapillary epithelia express mainly the "esophageal-type" keratins, while the papillary epithelia express "skin-type" keratins as well as some keratins reacting with a monoclonal antibody (AE13) to hair keratins. The AE13-reactive proteins of the mouse were found to be very similar to those of authentic mouse hair keratins. However, the corresponding protein of human tongue appears to be different from all known human keratins. This protein has a MW of 51K; it is relatively acidic; it is sulfhydryl-rich, as revealed by iodoacetic acid-induced charge and apparent size shift; it shares an epitope with all the known acidic human hair keratins; and it is associated with keratin fibrils in vivo. This protein may therefore be regarded as a novel type I "hard" keratin. These data establish that mammalian dorsal tongue epithelia can be divided into at least three compartments that undergo mainly "esophageal-", "skin-" and "hair"-types of differentiation. Different keratin filaments, e.g., those of the esophageal- and hair-types, exhibit strikingly different degrees of lateral aggregation, which can potentially account for the different physical strength and rigidity of various cellular compartments. Our data also suggest the possibility that variations in papillary structure in human and mouse may arise from different spatial arrangements of specific keratinocytes, and/or from the expression of specialized hair-related keratins.

Animals↗