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Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):4084-8.
Gene disruption of p27(Kip1) allows cell proliferation in the postnatal and adult organ of corti.
Lowenheim H, Furness DN, Kil J, Zinn C, Gultig K, Fero ML, Frost D, Gummer AW, Roberts JM, Rubel EW, Hackney CM, Zenner HP.
Department of Otolaryngology, University of Tubingen, Silcherstrasse 5, 72076 Tubingen, Germany. hubert.loewenheini-tuebingen.de
Hearing loss is most often the result of hair-cell degeneration due to genetic abnormalities or ototoxic and traumatic insults. In the postembryonic and adult mammalian auditory sensory epithelium, the organ of Corti, no hair-cell regeneration has ever been observed. However, nonmammalian hair-cell epithelia are capable of regenerating sensory hair cells as a consequence of nonsensory supporting-cell proliferation. The supporting cells of the organ of Corti are highly specialized, terminally differentiated cell types that apparently are incapable of proliferation. At the molecular level terminally differentiated cells have been shown to express high levels of cell-cycle inhibitors, in particular, cyclin-dependent kinase inhibitors [Parker, S. B., et al. (1995) Science 267, 1024-1027], which are thought to be responsible for preventing these cells from reentering the cell cycle. Here we report that the cyclin-dependent kinase inhibitor p27(Kip1) is selectively expressed in the supporting-cell population of the organ of Corti. Effects of p27(Kip1)-gene disruption include ongoing cell proliferation in postnatal and adult mouse organ of Corti at time points well after mitosis normally has ceased during embryonic development. This suggests that release from p27(Kip1)-induced cell-cycle arrest is sufficient to allow supporting-cell proliferation to occur. This finding may provide an important pathway for inducing hair-cell regeneration in the mammalian hearing organ.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10097167&dopt=Abstract
Brain Res Mol Brain Res. 1999 Mar 20;66(1-2):83-93.
Cloning and expression of Shaker alpha- and beta-subunits during inner ear development.
Rajeevan MS, Hu S, Sakai Y, Sokolowski BH.
Department of Otolaryngology, Head and Neck Surgery, MDCO16, University of South Florida, 12901 Bruce B. Downs Blvd., Tampa, FL 33612, USA.
Sensory cells of the chicken cochlea exhibit different ion channels relative to their position along the epithelium. One of these channels conducts an A-type potassium current which is found primarily in 'short' hair cells. Here, we report the first full length cloning and developmental expression of Shaker genes from this endorgan. Clones were obtained by screening a chicken (Gallus gallus) cochlea cDNA library, using probes made from RHK1 (i.e., Kvalpha1.4) cDNA, a Shaker homologue isolated from rat heart, and hKvbeta1.2 cDNA, a beta homologue isolated from human heart. Sequence analysis revealed a chick homologue of Kvalpha1.4, with a deduced amino acid similarity of 76-79% to mammalian Kvalpha1.4, and a chick homologue of Kvbeta1.1, with a similarity of 95% to mammalian Kvbeta1.1. In addition, we isolated a variant of cKvalpha1. 4 (cKvalpha1.4(m)) that differs in its untranslated regions and shows complete similarity in its coding region, except for the deletion of a single nucleotide. During development of the inner ear, reverse transcription-polymerase chain reaction (RT-PCR) studies show that the beta-subunit is expressed as early as embryonic day 3, whereas alpha- and beta-subunits are coexpressed on embryonic days 7 to 10, 14, and in adult. 1999 Elsevier Science B.V.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10095080&dopt=Abstract
J Dermatol Sci. 1999 Feb;19(2):123-5.
Minoxidil increases 17 beta-hydroxysteroid dehydrogenase and 5 alpha-reductase activity of cultured human dermal papilla cells from balding scalp.
Sato T, Tadokoro T, Sonoda T, Asada Y, Itami S, Takayasu S.
Department of Dermatology, Oita Medical University, Japan.
Minoxidil is known to induce hair growth in male pattern baldness, for which development androgen plays a central role. We studied the effect of minoxidil on testosterone metabolism by cultured dermal papilla cells from balding or nonbalding scalp and dermal fibroblasts. In all three groups, 17beta-hydroxysteroid dehydrogenase activity was much higher than 5alpha-reductase activity. Minoxidil increased 17beta-hydroxysteroid dehydrogenase activity by nearly 40% (P < 0.001) in dermal papilla cells of balding scalp, whereas the effect was less marked in dermal papilla cells from nonbalding scalp and dermal fibroblasts. 5alpha-Reductase activity was also slightly increased by minoxidil in dermal papilla cells from balding scalp. Again, the effect on 5alpha-reductase activity was insignificant in the other two groups of cells. Whether such modification of testosterone metabolism in dermal papilla cells of balding scalp by minoxidil is related to its therapeutic effect remains unknown.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10098703&dopt=Abstract
Acta Otolaryngol Suppl. 1998;539:28-33.
Thimerosal-induced Ca2+ mobilization in isolated guinea pig cochlear outer hair cells.
Chen L, Harada N, Yamashita T.
Department of Otolaryngology, Kansai Medical University, Osaka, Japan.
Intracellular calcium mobilization of isolated guinea pig cochlear outer hair cells (OHCs) was investigated using thimerosal, a -SH group oxidizing agent, and fura-2 fluorescence ratio imaging microscopy. In the presence of thimerosal, intracellular Ca2+ concentrations ([Ca2+]i) of OHCs were elevated in a dose-dependent manner. Even in Ca(2+)-free medium, Ca2+ response was still induced. The effects of thimerosal on [Ca2+]i were completely blocked and reversed by dithiothreiotol (DTT). Neither 1-100 microM ryanodine nor 5-20 mM caffeine altered the effects of thimerosal. Pretreatment with pertussis toxin (PTX) for 30 min did not affect the thimerosal-induced increase in [Ca2+]i. The increase in [Ca2+]i when Ca2+ was added during thimerosal application in Ca(2+)-free medium was almost completely blocked by 500 microM LaCl3, while nifedipine did not inhibit further increase in [Ca2+]i caused by thimerosal. Thus, oxidation of the -SH group of the OHC membrane can induce a Ca2+ release from intracellular Ca2+ stores, which are ryanodine- and caffeine-insensitive, and Ca2+ influx through non-specific Ca2+ channels, but not the nifedipine-sensitive Ca2+ channels. The possible oxidation of -SH group gated Ca2+ channels in OHCs is worthy of further study.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10095857&dopt=Abstract
The most ostensive feature that distinguishes us human from chimps and other primates is the lack of bodily hair. During evolutionary process, we have lost the majority of hair. Hair is no longer an essential part of our body, just like appendix. What little hair we still have on our scalp and a few other bodily parts is still regarded as significant for reasons other than biological necessity. Hair loss is naturally accompanied by aging process, although the extent of hair loss and the timing of onset vary widely among individuals. Thus, loss of hair and baldness is considered as a symbol of maturity or old age. Like winkles and other signs of aging, hair loss is not welcome by most people, because we don't welcome aging, and being perceived as an aging person. However, it is alopecia, or premature hair loss that especially concerns certain people.
Hair Million is a blend of Asian herbs that wards off hair loss and promotes hair growth. Of various approaches to hair restoration, Hair Million offers advantages including low cost compared with other methods or drugs, and safety, because it is made of safe and healthy herbs.
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