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At least 307 records · Page 17Linked to original sources

Abolition of the receptor potential response of isolated mammalian outer hair cells by hair-bundle treatment with elastase: a test of the tip-link hypothesis.

To test the hypothesis that the tip-links of hair-cell stereocilia are essential for mechanoelectrical transduction, tip-links of isolated outer hair cells (OHCs) of the guinea-pig cochlea were eliminated with a proteolytic enzyme, elastase, and the influence on the receptor potential measured with the whole-cell patch-clamp technique. Within 45 s of immersion of the hair bundle in 20 IU/ml elastase, the receptor potential in response to direct deflection of the hair bundle was irreversibly abolished. The electrical input impedance of the cell remained unchanged, implying that the channels of the basolateral membrane were not affected by elastase. The effect of elastase on the receptor potential was comparable to changes seen after mechanically induced hair-bundle damage. As a further control, a putative transduction-channel blocker, dihydrostreptomycin (68 microM), which does not affect tip-links, was applied to the hair bundle. Although the receptor potential was also blocked by dihydrostreptomycin, the effect was reversible. The results suggest that tip-links are required for mechanoelectrical transduction of mammalian OHCs.

Animals↗

Hair analysis of histamine after fluorescence labeling by column-switching reversed-phase liquid chromatography with electrospray ionization mass spectrometry and application to human hair.

Sensitive determination of histamine (HA) in hair was carried out by column-switching reversed-phase high-performance liquid chromatography coupled with electrospray ionization mass spectrometry (HPLC-ESI-MS). HA was labeled with excess amounts of 4-(N,N-dimethylaminosulfonyl)-7-fluoro-2,1,3-benzoxadiazole (DBD-F) at 60 degrees C for 30 min in a mixture of 0.1 M borax (pH 9.3) and acetonitrile (CH(3)CN). The resulting DBD-HA derivative was roughly separated by a Mightysil RP-18 GP (100 x 2mm i.d., 3 microm) with an acidic mobile phase containing 0.1% trifluoroacetic acid. DBD-HA in the fraction flowing due to a position change in the six-port column-switching valve was then completely separated by a Wakopak Navi C30 (150 x 2mm i.d., 5 microm) with 20 mM AcONH(4)-CH(3)CN (8:2). The mass spectrometer was operated in the selected reaction monitoring (SRM) mode for the product ion (m/z 292) obtained from MS-MS measurement using the protonated molecular ion [M+H](+) (m/z 337) as the precursor ion. Good linearity was achieved from the calibration curve obtained by plotting peak area ratios of the internal standard (HA-d(4)) against the injected amounts of HA (1.66-16.6 pmol, r(2)=0.999). The coefficients of variation, at 1.66- and 16.6-pmol injections, were 5.6 and 3.7%, respectively (n=6). Furthermore, the detection limit was 0.167 pmol. The efficiency of the recommended procedure was identified from the determination in the rat hair root after intraperitoneal administration of HA. The proposed method was applied to HA determination in the hair shaft of Dark Agouti rats and healthy volunteers. The variations in the concentrations in 1mg of hair shaft were 0.80-1.84 pmol (mean+/-SD=1.33+/-0.33, n=12) in rats and 0.94-72.3 pmol (17.2+/-21.5, n=16) in humans. The determination of HA in the plasma of rats and humans was also performed successfully by this method. Because the proposed method provides good precision and trace detection of HA in hair, the analytical technique seems to be applicable for the determination of various biogenic amines in hair.

Animals↗

A hot new twist to hair biology: involvement of vanilloid receptor-1 (VR1/TRPV1) signaling in human hair growth control.

The vanilloid receptor-1 (VR1, or transient receptor potential vanilloid-1 receptor, TRPV1) is activated by capsaicin, the key ingredient of hot peppers. TRPV1 was originally described on sensory neurons as a central integrator of various nociceptive stimuli. However, several human skin cell populations are also now recognized to express TRPV1, but with unknown function. Exploiting the human hair follicle (HF) as a prototypic epithelial-mesenchymal interaction system, we have characterized the HF expression of TRPV1 in situ and have examined TRPV1 signaling in organ-cultured human scalp HF and outer root sheath (ORS) keratinocytes in vitro. TRPV1 immunoreactivity was confined to distinct epithelial compartments of the human HF, mainly to the ORS and hair matrix. In organ culture, TRPV1 activation by capsaicin resulted in a dose-dependent and TRPV1-specific inhibition of hair shaft elongation, suppression of proliferation, induction of apoptosis, premature HF regression (catagen), and up-regulation of intrafollicular transforming growth factor-beta(2). Cultured human ORS keratinocytes also expressed functional TRPV1, whose stimulation inhibited proliferation, induced apoptosis, elevated intracellular calcium concentration, up-regulated known endogenous hair growth inhibitors (interleukin-1beta, transforming growth factor-beta(2)), and down-regulated known hair growth promoters (hepatocyte growth factor, insulin-like growth factor-I, stem cell factor). These findings strongly support TRPV1 as a significant novel player in human hair growth control, underscore the physiological importance of TRPV1 in human skin beyond nociception, and identify TRPV1 as a promising, novel target for pharmacological manipulations of epithelial growth disorders.

Apoptosis↗

Hair-MAP: a prototype automated system for forensic hair comparison and analysis.

This paper demonstrates the feasibility of the automation of forensic hair analysis and comparison task using neural network explanation systems (NNESs). Our system takes as input microscopic images of two hairs and produces a classification decision as to whether or not the hairs came from the same person. Hair images were captured using a NEXTDimension video board in a NEXTDimension color turbo computer, connected to a video camera. Image processing was done on an SGI indigo workstation. Each image is segmented into a number of pieces appropriate for classification of different features. A variety of image processing techniques are used to enhance this information. Use of wavelet analysis and the Haralick texture algorithm to pre-process data has allowed us to compress large amounts of data into smaller, yet representative data. Neural networks are then used for feature classification. Finally, statistical tests determine the degree of match between the resulting collection of hair feature vectors. An important issue in automation of any task in criminal investigations is the reliability and understandability of the resulting system. To address this concern, we have developed methods to facilitate explanation of neural network's behavior using a decision tree. The system was able to achieve a performance of 83% hair match accuracy, using 5 of the 21 morphological characteristics used by experts. This shows promise for the usefulness of a fuller scale system. While an automated system would not replace the expert, it would make the task easier by providing a means for pre-processing the large amount of data with which the expert must contend.

Algorithms↗

Growth factors in hair organ development and the hair growth cycle.

Growth factors are polypeptides that regulate growth and differentiation of many cell types. Different growth factor families including the epidermal growth factor (EGF)-related ligands, fibroblast growth factors (FGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), hepatocyte growth factor/scatter factor (HGF/SF), and platelet-derived growth factor (PDGF) have been shown to be crucial for the regulation of the hair cycle and hair growth. Growth factors and their receptors have been localized to the skin and hair follicles. Their biological activities on cells comprising the hair follicle have been tested in vitro and increasingly in transgenic mice. Herein we review selected important aspects of growth factors with regard to the hair organ, its development, and the hair growth cycle.

Animals↗

Hair cycle-dependent expression of hepatocyte growth factor (HGF) activator, other proteinases, and proteinase inhibitors correlates with the expression of HGF in rat hair follicles.

We previously reported that hepatocyte growth factor (HGF) had a stimulatory effect on hair growth in vivo and in vitro. The secreted inactive form of HGF is processed into an active form by serine proteinases such as HGF activator and urokinase. The mRNA expressions of various proteinases and their inhibitors in relation to HGF activation in hair growth were examined using animals with a synchronous hair cycle. Total RNA were extracted from the anterior dorsal skin of rats in different hair cycle stages, and mRNA expressions of the specific genes were compared using semiquantitative reverse transcription polymerase chain reaction. The mRNA of HGF, HGF activator, urokinase, plasminogen activator inhibitor (PAI)-1, nexin-1, matrix metalloproteinase (MMP)-2, and tissue inhibitor of metalloproteinase (TIMP)-1 were expressed strongly in anagen tissue and slightly in telogen tissue. Moreover, topical application of 1% minoxidil sulfate to the anterior dorsal skin of rats in telogen stimulated hair growth and increased the mRNA expressions of HGF and MMP-2. These findings suggest that some proteinases and their inhibitors, strongly expressed in anagen, may act as hair growth regulatory molecules, and may also be involved in processing the latent form of HGF.

Animals↗

Colonisation status of Malassezia pachydermatis on the hair and in the hair follicle of healthy beagle dogs.

Hair and hair follicle carriage of Malassezia pachydermatis was studied in 12 healthy beagle dogs. The yeast was isolated from hair clipped from the lip region at 13 sites in nine dogs but was less frequently recovered from the interdigital spaces on the forefeet and from two sites on the trunk. Population sizes at the lip were significantly greater (P < 0.01) than those at other sites. Skin biopsy specimens were obtained from the same sites and epidermal and follicular tissues dissected following immersion in 1 M CaBr(2). Epidermal carriage of M. pachydermatis was identified in nine biopsy specimens taken from five dogs. Hair follicle carriage was identified in five skin specimens (four foot, one lip) from three dogs. This study indicates that M. pachydermatis is readily recovered from the distal hair in healthy dogs and that hair follicle carriage is infrequent or that populations are low at that site.

Animals↗

Negative hair-bundle stiffness betrays a mechanism for mechanical amplification by the hair cell.

Hearing and balance rely on the ability of hair cells in the inner ear to sense miniscule mechanical stimuli. In each cell, sound or acceleration deflects the mechanosensitive hair bundle, a tuft of rigid stereocilia protruding from the cell's apical surface. By altering the tension in gating springs linked to mechanically sensitive transduction channels, this deflection changes the channels' open probability and elicits an electrical response. To detect weak stimuli despite energy losses caused by viscous dissipation, a hair cell can use active hair-bundle movement to amplify its mechanical inputs. This amplificatory process also yields spontaneous bundle oscillations. Using a displacement-clamp system to measure the mechanical properties of individual hair bundles from the bullfrog's ear, we found that an oscillatory bundle displays negative slope stiffness at the heart of its region of mechanosensitivity. Offsetting the hair bundle's position activates an adaptation process that shifts the region of negative stiffness along the displacement axis. Modeling indicates that the interplay between negative bundle stiffness and the motor responsible for mechanical adaptation produces bundle oscillation similar to that observed. Just as the negative resistance of electrically excitable cells and of tunnel diodes can be embedded in a biasing circuit to amplify electrical signals, negative stiffness can be harnessed to amplify mechanical stimuli in the ear.

Animals↗

Mechanical relaxation of the hair bundle mediates adaptation in mechanoelectrical transduction by the bullfrog's saccular hair cell.

Mechanoelectrical transduction by hair cells of the frog's internal ear displays adaptation: the electrical response to a maintained deflection of the hair bundle declines over a period of tens of milliseconds. We investigated the role of mechanics in adaptation by measuring changes in hair-bundle stiffness following the application of force stimuli. Following step stimulation with a glass fiber, the hair bundle of a saccular hair cell initially had a stiffness of approximately equal to 1 mN X m-1. The stiffness then declined to a steady-state level near 0.6 mN X m-1 with a time course comparable to that of adaptation in the receptor current. The hair bundle may be modeled as the parallel combination of a spring, which represents the rotational stiffness of the stereocilia, and a series spring and dashpot, which respectively, represent the elastic element responsible for channel gating and the apparatus for adaptation.

Acclimatization↗

Effects of extracellular Ca2+ concentration on hair-bundle stiffness and gating-spring integrity in hair cells.

When a hair cell is stimulated by positive deflection of its hair bundle, increased tension in gating springs opens transduction channels, permitting cations to enter stereocilia and depolarize the cell. Ca2+ is thought to be required in mechanoelectrical transduction, for exposure of hair bundles to Ca2+ chelators eliminates responsiveness by disrupting tip links, filamentous interstereociliary connections that probably are the gating springs. Ca2+ also participates in adaptation to stimuli by controlling the activity of a molecular motor that sets gating-spring tension. Using a flexible glass fiber to measure hair-bundle stiffness, we investigated the effect of Ca2+ concentration on stiffness before and after the disruption of gating springs. The stiffness of intact hair bundles depended nonmonotonically on the extracellular Ca2+ concentration; the maximal stiffness of approximately 1200 microN.m-1 occurred when bundles were bathed in solutions containing 250 microM Ca2+, approximately the concentration found in frog endolymph. For cells exposed to solutions with sufficient chelator capacity to reduce the Ca2+ concentration below approximately 100 nM, hair-bundle stiffness fell to approximately 200 microN.m-1 and no longer exhibited Ca2+-dependent changes. Because cells so treated lost mechanoelectrical transduction, we attribute the reduction in bundle stiffness to tip-link disruption. The results indicate that gating springs are not linearly elastic; instead, they stiffen with increased strain, which rises with adaptation-motor activity at the physiological extracellular Ca2+ concentration.

Acoustic Maculae↗

Cell death (apoptosis) in hair follicles and consequent changes in the width of hairs after irradiation of growing follicles.

Irradiation of anagen (growing) hair follicles results in a dose-dependent increase in the number of histologically identifiable fragments of dead cells (apoptotic fragments). The incidence of apoptotic fragments is linearly related to dose, increasing at a rate of 2.92 fragments per follicle section per Gy. The effects of doses of 0.2 Gy can be easily detected. Subjective attempts to associate clusters of fragments with dead or dying cells suggests that the number of fragments per cell increases with dose (about 1.7 fragments per cell after 1 Gy to about 2.7 fragments per cell after 5 Gy). There is a natural incidence of cell death in controls (0.13 +/- 0.06 fragments per follicle section with about 1.4 fragments per dead or dying cell). Damage to the follicle cells is expressed in the differentiated product of the follicle, the hair, by a reduction in width. This is probably the cellular basis for the production of dysplastic hairs. The hair width has been measured and is reduced by about 7 per cent for every gray of radiation. The value of the hair and hair follicles as potential biological dosimeters is discussed.

Animals↗

Testing human hair for drugs of abuse. II. Identification of unique cocaine metabolites in hair of drug abusers and evaluation of decontamination procedures.

Two unique metabolites of cocaine, cocaethylene and norcocaine, were identified by GC/MS in the hair of cocaine users. Their presence cannot be explained by environmental contamination; thus, their presence together with cocaine provides convincing evidence that cocaine is excreted in hair after active cocaine administration. The amount of cocaine in hair predominated over all metabolites generally by a factor of 5-10. Two washing procedures were evaluated for their efficiency in removal of cocaine from environmentally contaminated hair. Neither procedure completely removed cocaine, suggesting that false positives can result from environmental contamination. Analysis of the methanolic wash of the hair of cocaine users also revealed the presence of cocaine metabolites, indicating that washing removes cocaine from the interior as well as from the exterior surface of hair during decontamination procedures.

Adult↗

Atomic force microscopy of human hair cuticles: a microscopic study of environmental effects on hair morphology.

We have used an atomic force microscope to provide quantitative real-time analysis of human hair morphologic changes under ambient conditions. This form of microscopy combines the lateral resolution of an electron microscope and the flexibility of a light microscope. Three experiments were performed: a study of hair morphology in air versus water, a kinetic study of hair hydration, and a determination of how pH changes affect hair morphology. The overlapping keratinized cells that form the hair cuticle spread out between 50 and 150% when hydrated, compared to a total shaft diameter change of 10%. This hydration reaches a saturation point within the first few minutes after immersion. Also, hair swells much more at higher pH.

Adult↗

Distribution of two basement membrane proteoglycans through hair follicle development and the hair growth cycle in the rat.

The distribution of two distinct populations of basement membrane proteoglycans has been monitored through hair growth development in the rat embryo and subsequent hair growth cycle. An antiserum against a small heparan sulfate proteoglycan uniformly stained the dermal-epidermal junction of embryonic rats throughout the period of hair follicle formation. On the other hand, monoclonal antibodies recognizing a basement membrane-specific chondroitin sulfate proteoglycan only weakly stained 16-d embryo dermal-epidermal junction, but strong staining was associated with hair follicle buds as they developed. Through the hair growth cycle, it was found that the heparan sulfate proteoglycan persisted around the follicles, while the chondroitin sulfate proteoglycan decreased in amount through catagen until it was undetectable at the base and dermal papilla of the telogen follicle. As anagen commenced, expression of the chondroitin sulfate proteoglycan was again demonstrated. It therefore appears that a basement membrane-specific proteoglycan shows variation in its distribution in rat skin, expression correlating with morphogenetic activity in hair follicles. It is possible that this newly described basement membrane component is involved in the complex processes of dermal-epidermal interaction that lead to skin appendage formation and growth.

Aggrecans↗

Hair fibrous protein compositions in some hereditary hair abnormalities determined by two-dimensional polyacrylamide gel electrophoresis.

S-carboxymethylated (SCM) fibrous proteins (FPs) from the scalp hairs of the three different hereditary hair abnormalities (trichorrhexis invaginata in Netherton's syndrome, pili trianguli et canaliculi in uncombable hair syndrome, and fine hair in anhidrotic ectodermal dysplasia) were analyzed by two-dimensional polyacrylamide gel electrophoresis. Comparison of the SCM FP compositions of the three hair abnormalities with that of the normal revealed that the SCM FP compositions of these three abnormal hairs were all electrophoretically different from each other and that of the normal.

Child↗

Proliferating activity of the hair follicular melanocytes at the early and anagen III stages in the hair growth cycle: detection by immunocytochemistry for bromodeoxyuridine combined with DOPA reaction cytochemistry.

In order to demonstrate the existence of proliferating activity in hair follicular melanocytes during the early and anagen III stages, immunocytochemistry for bromodeoxyuridine (BrdU) incorporated in the nuclei of the melanocytes for 1 hr was undertaken at the light and electron microscopic levels in combination with DOPA reaction cytochemistry. Light microscopically, about 30% of the nuclei of the DOPA reaction positive melanocytes at the anagen III stage of the hair growth cycle were labeled by anti-BrdU antibody. These melanocytes were observed in about one hundred hair follicles. Electron microscopically, the nuclei of a few undifferentiated melanocytes at the anagen II stage were labeled by anti-BrdU antibody-affiliated secondary antibody-gold particles. At the anagen III stage, localization of the immunogold particles in the DNA replication domains of the nuclei of the undifferentiated and redifferentiating melanocytes covered the patterns of the early, middle, and late S-phase. These findings suggest that the hair follicular melanocytes begin proliferation at the anagen II stage and that the melanocytes proliferate actively at the anagen III stage to repopulate the hair matrix during subsequent hair growth.

Animals↗

Diseases on hair follicles leading to hair loss part I: nonscarring alopecias.

Hair follicles are unique structures with exceptional regenerative potential. They are believed to be crucial for epidermal homeostasis and reepithelialization after damage to human skin. Like other, more active and quickly proliferating organ systems, hair follicles may be easily disturbed in their normal growth cycle by systemic and local influences, including specific skin diseases. This may lead to hair loss, a very common complaint in men and women. The difficulties in reviewing the diseases of hair follicles lay in the long list of different etiologic factors (infectious, autoimmune, inflammatory, neoplastic, physical, chemical, congenital) and a still missing classification system according to etiopathogenetic principles. In this article (Part I of II), the structure and function of hair follicles, the diagnostic approach to diseases causing hair loss, and the most common nonscarring alopecias (telogen effluvium, anagen effluvium, androgenetic alopecia, and alopecia areata) are reviewed in regard to pathogenesis, clinical findings, and current options of treatment. Part II will focus on scarring alopecias.

Alopecia↗

Active hair bundle movements in auditory hair cells.

The frequency selectivity of mammalian hearing depends on not only the passive mechanics of the basilar membrane but also an active amplification of the mechanical stimulus by the cochlear hair cells. The common view is that amplification stems from the somatic motility of the outer hair cells (OHCs), changes in their length impelled by voltage-dependent transitions in the membrane protein prestin. Whether this voltage-controlled mechanism, whose frequency range may be limited by the membrane time constant, has the band width to cover the entire auditory range of mammals is uncertain. However, there is ample evidence for an alternative mode of force generation by hair cells of non-mammals, such as frogs and turtles, which probably lack prestin. The latter process involves active motion of the hair bundle underpinned by conformational changes in the mechanotransducer (MT) channels and activation of one or more isoforms of myosin. This review summarizes evidence for active hair bundle motion and its connection to MT channel adaptation. Key factors for the hair bundle motor to play a role in the mammalian cochlea include the size and speed of force production.

Animals↗