References: Hair growth and hair loss
Hear Res. 1998 Jan;115(1-2):143-8.
Receptor-targeted delivery of an intracellular toxin to outer hair cells by fibroblast growth factor.
Dazert S, Baird A, Ryan AF.
Department of Surgery/Otolaryngology, UCSD School of Medicine and Veterans Administration Medical Center, La Jolla, CA 92093-0666, USA.
The presence and distribution of functional, high-affinity receptors for fibroblast growth factors (FGFs) in the neonatal organ of Corti were probed using the intracellular toxin saporin conjugated to basic FGF (FGF-2). FGFs that bind to high-affinity FGF receptors are internalized as part of the normal process of receptor inactivation. The receptor can thus be used for the targeted delivery of molecules conjugated to FGF into the cytoplasm. Incubation of postnatal day 5 (P5) rat organ of Corti cultures with FGF-saporin caused a dose dependent destruction of outer hair cells, Deiters cells and outer pillar cells. Inner hair cells and other cells were unaffected. Organ of Corti cultures at P0 and P10 showed much less damage than at P5. The results suggest that outer hair cells and adjacent supporting cells in the organ of Corti transiently express high-affinity FGF receptors, and that these receptors can mediate the intracellular delivery of bioactive molecules.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9472743&dopt=Abstract
Hear Res. 1998 Jan;115(1-2):217-23.
Loss of spiral ganglion cells as primary manifestation of aminoglycoside ototoxicity.
Sone M, Schachern PA, Paparella MM.
Department of Otorhinolaryngology, Nagoya University School of Medicine, Japan.
Although pulmonary infections caused by Pseudomonas aeruginosa can hardly be eradicated in patients with cystic fibrosis (CF, the most common genetic disease among Caucasians), these patients are mainly treated with intravenous and nebulized tobramycin. Long-term treatment with tobramycin, however, may induce ototoxic effects. We assessed the clinical histories and postmortem temporal bones of six patients with CF for signs of this ototoxicity. Four bones showed typical manifestations of ototoxicity induced by aminoglycosides (AGs): loss of hair cells in the lower turns, and degeneration of ganglion cells. Six bones revealed no loss or scattered loss of hair cells, however, degeneration of the spiral ganglion cells was observed. This suggests that degeneration of the spiral ganglion may occur as a primary manifestation in some cases of ototoxicity due to aminoglycosides. Recent reports have shown that trophic factors (neurotrophins and acidic fibroblast growth factor) interacting with hair cells and the spiral ganglion protect the inner ear from damage. It may be that disturbances in supply of such trophic factors caused degeneration of ganglion cells without loss of hair cells in the cases we studied.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9472750&dopt=Abstract
Mol Carcinog. 1998 Jan;21(1):2-12.
Severe follicular hyperplasia and spontaneous papilloma formation in transgenic mice expressing the neu oncogene under the control of the bovine keratin 5 promoter.
Bol D, Kiguchi K, Beltran L, Rupp T, Moats S, Gimenez-Conti I, Jorcano J, DiGiovanni J.
Department of Carcinogenesis, University of Texas M.D. Anderson Cancer Center, Smithville 78957, USA.
Transgenic mice were developed to explore the role of the erbB2 during epithelial homeostasis and tumorigenesis, through targeted expression of the neu oncogene (neu*). Expression of a neu* cDNA was targeted to the basal layer of skin epidermis as well as other epithelial tissues of transgenic mice via the bovine keratin 5 promoter. Two transgenic founders were obtained that were morphologically distinguishable from non-transgenic littermates by their visibly thickened skin and patchy hair growth by day 3 after birth. The presence of the transgene was confirmed by polymerase chain reaction analysis of tail DNA and immunofluorescence analysis of neu* protein in skin sections. Histological evaluation revealed significant hyperplasia of the follicular and interfollicular epidermis, the abnormal presence of horny material in the dermis and hypodermis, and a dramatic increase in epidermal proliferation. Many areas of the dermis involving this abnormal epithelial proliferation exhibited a squamous cell carcinoma-like appearance. In addition, there was unusual proliferation of the sebaceous glands. One founder died at day 14 and the other at day 20. The latter founder had two papillomas at the time of death. Additional phenotypic changes resulting from the expression of neu* in other tissues included hyperkeratosis in the forestomach and esophagus.In addition, there was a lack of distinction of the cortical-medullary boundaries and an increased rate of cell death in lymphocytes in the thymus. The phenotypic changes in these other tissues correlated with transgene expression. The data suggest that erbB2 signaling has an important role in epidermal proliferation. In addition, the data provide strong support for a role for erbB2 signaling during epidermal carcinogenesis in mouse skin.
online pharmacy ref. source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9473766&dopt=Abstract
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