Estimation of size of clonal unit for keratinocytes in normal human
skin.
Chaturvedi V, Chu MD S, Carrol BS M, Brenner BS JW, Nickoloff BJ.
Department of Pathology, Loyola University Medical Center, Maywood,
IL, USA. |
Arch Pathol Lab Med 2002 Apr;126(4):420-4 Abstract quote
OBJECTIVE: It has been suggested that keratinocyte (KC) stem cells
reside at the epicenter of a clonal population of cells. To estimate
the territory or surface area covered by a single stem-cell-derived
KC population in human skin, clonal skin maps were created from 3 healthy
adult women and from normal skin of a psoriatic patient.
DESIGN: Two hundred fifty-eight punch biopsy samples of various sizes
(ranging from 2 to 8 mm in diameter) were analyzed for clonality employing
X chromosome inactivation patterns at the human androgen receptor gene
(HUMARA) locus. DNA was isolated and clonality established by significant
decrease of either maternal or paternal X chromosome band patterns following
restriction enzyme digestion, polymerase chain reaction amplification,
and gel electrophoresis.
RESULTS: Fifty-three (41%) of 128 two-mm biopsies were clonal, whereas
only 6 (14%) of 43 three-mm, 5 (14%) of 36 four-mm, and 3 (8%) of 35
five-mm biopsies revealed a clonal population of KCs. By contrast, in
5 different biopsies from a psoriatic patient, including 4- or 5-mm
sizes, all but 1 were clonal; even an 8-mm biopsy contained a clonal
population of KCs. Mantel-Haenszel chi(2) analysis revealed a P value
of.001, reflecting a strong trend in probability for presence of a single
clone of KCs as related to size of the biopsy sample. By sequentially
analyzing 30 contiguous 2-mm biopsy samples within a given strip of
skin, 10 clonal domain changes, as reflected in maternal versus paternal
switches, were observed.
CONCLUSIONS: These results provide direct evidence of a clonal population
of KCs in normal and psoriatic lesion-free skin, and indicate that a
clonal epidermal unit of KCs frequently can be detected in small biopsies
(2 mm), but that in normal skin sampling, overlapping clones are apparently
present in larger (ie, 4-5-mm) biopsies, producing nonclonal patterns.
The clonal domain of progeny in normal skin has a rather limited territorial
boundary (2 mm in diameter). However, in lesion-free skin from a psoriatic
patient, there may be clonal expansion of KCs due to perturbation in
epidermopoiesis and/or stem cell distribution. |
|
Desmoglein as a target in autoimmunity and infection.
Amagai M.
Department of Dermatology, Keio University School of Medicine.
|
J Am Acad Dermatol 2003 Feb;48(2):244-52 Abstract quote
Clinical phenotypes of most diseases are complex. However, once the
mechanism behind the scene is clarified, the nature shows amazing beauty.
There is a simple logic behind a complex disease. The exact molecular
mechanism of the blister formation in staphylococcal scalded skin syndrome
(SSSS) remained to be elucidated for 3 decades since exfoliative toxin
was discovered by Melish and Glasgow in 1970.
A knowledge accumulated to understand the pathogenesis of pemphigus
and cell-cell adhesion of keratinocytes led us to solve this question.
Desmoglein 1, which is a cadherin type cell-cell adhesion molecule in
desmosomes, is targeted in two different skin diseases, pemphigus foliaceus,
and SSSS. In pemphigus foliaceus IgG autoantibodies are developed against
desmoglein 1 and inhibit its adhesive function with resultant blister
formation in the superficial epidermis.
In SSSS, exfoliative toxin produced by Staphylococcus aureus specifically
binds and cleaves desmoglein 1 with resultant blister formation at the
identical site. |
p63 expression in normal human epidermis and epidermal appendages and
their tumors.
Tsujita-Kyutoku M, Kiuchi K, Danbara N, Yuri T, Senzaki H,
Tsubura A.
Departments of Pathology II and Plastic and Reconstructive
Surgery, Kansai Medical University, Moriguchi, Osaka, Japan.
|
J Cutan Pathol 2003 Jan;30(1):11-7 Abstract quote
BACKGROUND: p63, a member of the p53 gene family, is expressed in basal
cells of several different organs.
METHODS: The immunoreactivity of p63 was examined in normal human epidermis
and epidermal appendages and their tumors, and compared with proliferative
activity as evaluated by Ki-67.
RESULTS: In normal skin, p63 expression was seen in basal/suprabasal
cells of the epidermis, outer root sheath and hair matrix cells of the
hair follicle, seboblast situated in the outermost layer of sebaceous
glands, and outer layer cells of the ductal portion and myoepithelial
cells of the secretory portion of the sweat glands. p63 expression was
confined to the cells forming a continuous basal rim along the normal
epithelial structure. In tumors, p63 expression resembled that in normal
tissue in that tumor components originating from p63-positive cells
were constantly positive for p63. In normal and tumor tissues, not all
p63-positive cells were positive for Ki-67.
CONCLUSIONS: p63 expression may be a marker of basal/progenitor cells
in tumors of epidermis and epidermal appendages, and may be a diagnostic
marker of these tumors. |
