1.Livedoid vasculopathy and its association with factor V Leiden mutation.
Angeline Anning YONG ; Audrey Wei Hsia TAN ; Yoke Chin GIAM ; Mark Boon Yang TANG
Singapore medical journal 2012;53(12):e258-60
Livedoid vasculopathy is a rare chronic relapsing disorder characterised by recurrent painful thrombotic and vasculitic ulcers on the legs. We present the cases of two Indian women with livedoid vasculopathy that were found to be associated with an underlying factor V Leiden heterozygous mutation. There were no other thrombotic manifestations, and livedoid vasculopathy was the sole presenting feature of the factor V Leiden mutation, although this could also be coincidental. Initial treatment with high-dose immunosuppressive therapy was suboptimal, and the addition of pentoxifylline and antiplatelet therapy was crucial in achieving disease control and remission. These cases highlight the possible association with an underlying prothrombotic disorder, such as factor V Leiden mutation, in patients with livedoid vasculopathy. Although this association is relatively uncommon, it is more relevant to Indian patients, as the presence of factor V Leiden mutation is highest in this ethnicity as compared to the local Malay and Chinese populations.
Adult
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Blood Vessels
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pathology
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DNA
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genetics
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Factor V
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genetics
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metabolism
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Female
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Humans
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Leg Ulcer
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blood
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genetics
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pathology
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Livedo Reticularis
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blood
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diagnosis
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genetics
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Point Mutation
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Polymerase Chain Reaction
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Skin
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blood supply
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Skin Diseases, Vascular
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blood
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genetics
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pathology
2.Dermal fibroblast expression of stromal cell-derived factor-1 (SDF-1) promotes epidermal keratinocyte proliferation in normal and diseased skin.
Chunji QUAN ; Moon Kyun CHO ; Yuan SHAO ; Laurel E MIANECKI ; Eric LIAO ; Daniel PERRY ; Taihao QUAN
Protein & Cell 2015;6(12):890-903
Stromal cells provide a crucial microenvironment for overlying epithelium. Here we investigated the expression and function of a stromal cell-specific protein, stromal cell-derived factor-1 (SDF-1), in normal human skin and in the tissues of diseased skin. Immunohistology and laser capture microdissection (LCM)-coupled quantitative real-time RT-PCR revealed that SDF-1 is constitutively and predominantly expressed in dermal stromal cells in normal human skin in vivo. To our surprise, an extremely high level of SDF-1 transcription was observed in the dermis of normal human skin in vivo, evidenced by much higher mRNA expression level than type I collagen, the most abundant and highly expressed protein in human skin. SDF-1 was also upregulated in the tissues of many human skin disorders including psoriasis, basal cell carcinoma (BCC), and squamous cell carcinoma (SCC). Double immunostaining for SDF-1 and HSP47 (heat shock protein 47), a marker of fibroblasts, revealed that fibroblasts were the major source of stroma-cell-derived SDF-1 in both normal and diseased skin. Functionally, SDF-1 activates the ERK (extracellular-signal-regulated kinases) pathway and functions as a mitogen to stimulate epidermal keratinocyte proliferation. Both overexpression of SDF-1 in dermal fibroblasts and treatment with rhSDF-1 to the skin equivalent cultures significantly increased the number of keratinocyte layers and epidermal thickness. Conversely, the stimulative function of SDF-1 on keratinocyte proliferation was nearly completely eliminated by interfering with CXCR4, a specific receptor of SDF-1, or by knock-down of SDF-1 in fibroblasts. Our data reveal that extremely high levels of SDF-1 provide a crucial microenvironment for epidermal keratinocyte proliferation in both physiologic and pathologic skin conditions.
Adult
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Cell Proliferation
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Chemokine CXCL12
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genetics
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Epidermal Cells
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Epidermis
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pathology
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Extracellular Signal-Regulated MAP Kinases
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metabolism
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Fibroblasts
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metabolism
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Gene Expression Regulation
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Humans
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Keratinocytes
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cytology
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pathology
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Signal Transduction
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Skin Diseases
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genetics
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pathology
3.Rosai-Dorfman disease: clinicopathologic, immunohistochemical and etiologic study of 16 cases.
Jian-bo YU ; Wei-ping LIU ; Zhuo ZUO ; Yuan TANG ; Dian-ying LIAO ; Hong JI ; Yan-qiong BAI ; Shi-hui LI ; Chang-qing LU ; Hong-bo LUO
Chinese Journal of Pathology 2007;36(1):33-38
OBJECTIVESTo study the clinicopathologic features of Rosai-Dorfman disease (RDD), expression of various antigens, human herpes virus type 8 (HHV8), human papillomavirus (HPV)-DNA and Epstein-Barr virus (EBV)-mRNA, and compare the findings with those in the literature.
METHODSThe clinicopathologic findings of 16 Rosai-Dorfman disease cases were retrospectively reviewed. Immunohistochemical study for S-100 protein, CD68 (PG-M1), CD163, CD21, CD1a, CD20, CD45RO, CD4, CD8, M-CSF and HHV8 was carried out in 9 of the 16 cases. In-situ hybridization for EBV-mRNA and HPV-DNA was also performed.
RESULTSThe male-to-female ratio of the patients was 4.33:1. Amongst the 16 cases studied, 62.5% (10/16) presented nodal RDD, with cervical lymph node predominantly involved. Half of these cases had affected lymph nodes in more than one anatomic site. Extranodal RDD represented 37.5% (6/16) of the cases. The relapse rate of extranodal RDD was higher than that of nodal RDD. Histologically, nodal RDD was characterized by dilated sinuses filled with large polygonal histiocytes which contained lymphocytes and plasma cells. For extranodal lesions, various degrees of stromal fibrosis were seen in association with mixed inflammatory cells (especially plasma cells). The large polygonal histiocytes varied in number and were distributed in clusters or patches. Immunohistochemical study showed that the abnormal histiocytes were strongly positive for S-100 protein. They also expressed CD68, CD163 and M-CSF, but were negative for CD1a, CD21 and HHV8. The lymphocytes in cytoplasm of these histiocytes were positive for both T and B cell markers (with T cell predominance, including a mixture of CD4- and CD8-positive cells). HPV-DNA and EBV-mRNA were not detected by in-situ hybridization. To date, 62 cases of RDD have been reported in mainland China, including 34 cases of nodal RDD and 18 cases of extranodal RDD. The remaining 10 cases involved both lymph nodes and extranodal sites. Compared with overseas reports, RDD occurring in China tended to affect older patients and with slight male predilection.
CONCLUSIONSRosai-Dorfman disease is relatively rare in China. Pathologic diagnosis of extranodal RDD may be difficult. The demographic data of RDD in China, including age and sex of patients, are different from those in the literature.
Adolescent ; Adult ; Aged ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Bone Diseases ; metabolism ; pathology ; virology ; Child ; DNA, Viral ; analysis ; Female ; Follow-Up Studies ; Herpesvirus 8, Human ; genetics ; isolation & purification ; Histiocytosis, Sinus ; metabolism ; pathology ; virology ; Humans ; Immunohistochemistry ; Lymph Nodes ; pathology ; Macrophage Colony-Stimulating Factor ; metabolism ; Male ; Middle Aged ; Nose Diseases ; metabolism ; pathology ; virology ; RNA, Viral ; analysis ; Receptors, Cell Surface ; metabolism ; Retrospective Studies ; S100 Proteins ; metabolism ; Skin Diseases ; metabolism ; pathology ; virology ; Young Adult
4.Expression and Modulation of LL-37 in Normal Human Keratinocytes, HaCaT cells, and Inflammatory Skin Diseases.
Ji Eun KIM ; Beom Joon KIM ; Mi Sook JEONG ; Seong Jun SEO ; Myeung Nam KIM ; Chang Kwun HONG ; Byung In RO
Journal of Korean Medical Science 2005;20(4):649-654
Defensins and cathelicidins (LL-37) are major antimicrobial peptides (AMPs) of the innate immune system of the human skin. In normal non-inflamed skin these peptides are negligible, but their expression can be markedly increased in inflammatory skin disease such as psoriasis. We designed this study to identify the expressions of LL-37 in normal human keratinocyte (NHK) and HaCaT cells after exposure to stimulants and to investigate difference of LL-37 expression accompanied with cell differentiation status, and come to understand difference of susceptibility to infection in atopic dermatitis and psoriasis. Expressions of LL-37 in NHKs and HaCaT cells were evaluated by using RT-PCR, Western blotting, and immunohistochemical (IHC) staining at 6, 12, and 24 hr post stimulation after exposure to Ultraviolet B irradiation and lipopolysaccharide. And expression of LL-37 in skin biopsy specimens from patients with atopic dermatitis and psoriasis was determined by immunohistochemical analysis. In time-sequential analyses of LL-37 expression revealed that LL-37 was expressed in NHKs, but not in HaCaT cells. IHC analysis confirmed the presence of abundant LL-37 in the epidermis of psoriasis. Therefore we deduced that expression of LL-37 is affected by UV irradiation, bacterial infection, and status of cell differentiation.
Antimicrobial Cationic Peptides/analysis/*genetics
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Blotting, Western
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Cell Line
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Cells, Cultured
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Comparative Study
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Defensins/analysis/genetics
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Dose-Response Relationship, Drug
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Gene Expression/drug effects/radiation effects
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Humans
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Immunohistochemistry
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Keratinocytes/cytology/*metabolism
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Lipopolysaccharides/pharmacology
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Male
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RNA, Messenger/genetics/metabolism
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Research Support, Non-U.S. Gov't
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Reverse Transcriptase Polymerase Chain Reaction
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Skin/cytology/metabolism
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Skin Diseases/*genetics/metabolism/pathology
5.Expression of progesterone receptor in human keratinocytes.
Sungbin IM ; Eun So LEE ; Wankee KIM ; Jisub SONG ; Jaehyun KIM ; Miok LEE ; Won Hyoung KANG
Journal of Korean Medical Science 2000;15(6):647-654
Despite the various responses of human skin to female sex hormones, cellular and subcellular targets and the mechanisms of action of estrogen and progesterone in human skin are not well understood. The detection of estrogen receptor (ER) and progesterone receptor (PR) in the skin is of great importance to understand the effect of estrogen and progesterone. In primary cultures of human keratinocytes, expression of ER and PR was monitored by immunocytochemistry and reverse transcriptase polymerase chain reaction (RT-PCR). Paraffin embedded skin tissues were stained with monoclonal antibodies to human ER and PR by immunohistochemistry. Cultured human keratinocytes expressed cytoplasmic PR protein and PR mRNA transcripts. By contrast, ER was detected only at the mRNA level. Suprabasal keratinocytes from samples of pruritic urticarial papules, plaques of pregnancy (PUPPP) and psoriasis were stained positively only for PR, while those from samples of erythema nodosum were negative for both ER and PR. Lesional epidermis of PUPPP showed positive PR immunoreactivity, while nonlesional epidermis did not. No other cells in the normal human skin were stained with ER and PR. The present study suggests that by expressing PR human keratinocytes act as targets for progesterone action.
Adolescence
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Adult
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Aged
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Cells, Cultured
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Female
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Gene Expression
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Human
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Immunoenzyme Techniques
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Infant
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Keratinocytes/metabolism*
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Keratinocytes/cytology
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Male
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Middle Age
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Receptors, Estrogen/genetics
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Receptors, Estrogen/biosynthesis
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Receptors, Progesterone/genetics*
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Receptors, Progesterone/biosynthesis
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Reverse Transcriptase Polymerase Chain Reaction
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Sequence Analysis, DNA/methods
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Skin/pathology
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Skin/metabolism
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Skin Diseases/metabolism