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J Invest Dermatol 2002 Dec;119(6):1237-43

Loss of cell adhesion in Dsg3bal-Pas mice with homozygous deletion mutation (2079del14) in the desmoglein 3 gene.


Pemphigus encompasses a group of autoimmune blistering diseases with circulating pathogenic autoantibodies recognizing several proteins, including the desmosomal cadherin, desmoglein 3. Targeted disruption of the Dsg3 gene by homologous recombination (Dsg3tm1stan) in mouse results in fragility of the skin and oral mucous membranes, analogous to the human disease. In addition, the Dsg3tm1stan mice develop phenotypic runting and hair loss, identical to that of the mouse mutant, Dsg3bal-2J. The Dsg3bal-2J mice are homozygous for a 1 bp insertion (2275insT) in the Dsg3 gene resulting in a nonfunctional Dsg3 mRNA. In this study, we characterized an allelic mutation, Dsg3bal-Pas, with clinical features similar to those in Dsg3bal-2J. We have identified a 14 bp deletion in exon 13 of the Dsg3 gene resulting in a frameshift and premature termination codon 7 bp downstream from the site of the deletion and causing a truncation of the desmoglein 3 polypeptide by 199 amino acids, eliminating virtually all of the intracellular domain. We demonstrate that, although a Dsg3 mRNA transcript was detectable in Dsg3bal-Pas skin, the corresponding protein for desmoglein 3 was completely absent in the oral mucosal epithelium of homozygous Dsg3bal-Pas compared with that of +/Dsg3bal-Pas mice. No significant changes in the expression of desmogleins 1 and 2 were detected. To elucidate a potential mechanism causing loss of cell adhesion in the Dsg3bal-Pas mice, we generated a myc-tagged truncated Dsg3bal-Pas desmoglein 3 protein and expressed it in keratinocytes. The myc-tagged truncated Dsg3bal-Pas desmoglein 3 protein was found predominantly in the cytoplasm possibly due to increased proteolytic degradation. Cell surface staining was also detected but was jagged, not linear along the cell-cell border like that observed for the full-length desmoglein 3. The expression of the myc-tagged truncated Dsg3bal-Pas desmoglein 3 protein resulted in a reduction in staining of other desmosomal proteins, including desmoglein 1 and 2, plakophilin 2, and plakoglobin. In addition, the cells expressing myc-tagged truncated Dsg3bal-Pas desmoglein 3 protein underwent dramatic changes in cell morphology and exhibited striking extensive filopodia. Collectively, these data showed that the perturbation of desmoglein 3 found in the Dsg3bal-Pas mice resulted in disadhesion of keratinocytes manifested with blistering phenotype.


Bone Marrow Transplant 2002 Nov;30(9):593-7

Relationship between irreversible alopecia and exposure to cyclophosphamide, thiotepa and carboplatin (CTC) in high-dose chemotherapy.


Reversible alopecia is a commonly observed, important and distressing complication of chemotherapy. Permanent alopecia, however, is rare after standard-dose therapy, but has occasionally been observed after high-dose chemotherapy with cyclophosphamide, thiotepa and carboplatin (CTC). We evaluated the relationships between total exposure to these three compounds and their different metabolites in the high-dose CTC regimen, and the subsequent development of irreversible alopecia. Twenty-four patients received two or three courses of high-dose CTC, each followed by peripheral blood progenitor cell transplantation. Plasma levels of cyclophosphamide, its active metabolite 4-hydroxycyclophosphamide, thiotepa, its active metabolite tepa, and carboplatin were determined, and the area-under-the-plasma concentration-versus-time curves (AUC) of the compounds were calculated. Eight of the 24 patients included in the study developed permanent alopecia, while seven had normal hair regrowth and nine patients developed incomplete and/or thin hair regrowth. The carboplatin AUC and the summed AUC of thiotepa and tepa were both significantly associated with increasing irreversibility of hair loss. These results suggest that high exposure to carboplatin and the sum of the thiotepa and tepa exposure may lead to the development of permanent alopecia. This knowledge could guide therapeutic drug monitoring in order to prevent the occurrence of permanent alopecia and thereby improve the patients' quality of life.


Ann Dermatol Venereol 2002 May;129(5 Pt 2):841-4

The hair follicle as a target for gene therapy


The hair follicle possesses progenitor cells required for continuous hair follicle cycling and for epidermal keratinocytes, melanocytes and Langerhans cells. These different cell types can be the target of topical gene delivery in the skin of the mouse. Using a combination of liposomes and DNA, we demonstrate the feasibility of targeting hair follicle cells in human scalp xenografts. We consider liposome composition and stage of the hair cycle as important parameters influencing transfection of human hair follicles. Transfection is possible only during the early anagen phase. Factors and obstacles for the use of gene therapy in treating alopecia and skin diseases are discussed. A theoretical framework for future treatment of cutaneous and systemic disorders using gene therapy is presented.


Dermatol Surg 2002 Aug;28(8):720-8

Follicular unit extraction: minimally invasive surgery for hair transplantation.


BACKGROUND: Follicular Unit Transplantation (FUT) is performed using large numbers of naturally occuring individual follicular units obtained by single-strip harvesting and stereo-microscopic dissection. Donor wound scarring from strip excision, although an infrequent complication, still concerns enough patients that an alternative solution is warranted. OBJECTIVE: The purpose of this paper is to introduce Follicular Unit Extraction (The FOX Procedure), in which individual follicular units are removed directly from the donor region through very small punch excisions, and to describe a test (The FOX Test) that determines which patients are candidates for this procedure. This paper explores the nuances, limitations, and practical aspects of Follicular Unit Extraction (FUE). METHODS: FUE was performed using 1-mm punches to separate follicular units from the surrounding tissue down to the level of the mid dermis. This was followed by extraction of the follicular units with forceps. The FOX test was developed to determine which patients would be good candidates for the procedure. The test was performed on 200 patients. Representative patients who were FOX-positive and FOX-negative were studied histologically. RESULTS: The FOX Test can determine which patients are suitable candidates for FUE. Approximately 25% of the patients biopsied were ideal candidates for FUE and 35% of the patients biopsied were good candidates for extraction. CONCLUSION: FUE is a minimally invasive approach to hair transplantation that obviates the need for a linear donor incision. This technique can serve as an important alternative to traditional hair transplantation in certain patients.


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Related Web resources:


  • What is hair?
  • Curly Hair
  • Biology of hair growth and development.
  • The phenomenon of hair loss.
  • Methods and treatments for hair loss and baldness.
  • Drugs and hair transplantation surgery for hair loss and baldness.
  • Hair loss linked to other health problems.
  • Baldness by choice and fashion.
  • Alopecia info.
  • Alopecia treatment info.
  • Alopecia treatment info.
  • Hair care info.
  • Hair loss and alopecia research articles: abstracts and source links.



    DHEA has been suggested to provide numerous potential benefits. DHEA (or dehydroepiandrosterone) is converted into androgens (male hormones) or estrogens (female hormones) in the cells.





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