Background: The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives: We...Background: The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives: We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. Methods: Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. Results: A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of < 15 showed serum levels of 705 ± 120 ng mL- 1 (mean ± SEM, n = 18), those with a PASI of ≥ 15 showed levels of 1315 ± 150 ng mL- 1 (n = 32) while controls presentedwith 365± 50 ng mL- 1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional,nonpsoriatic interfollicular epidermis. Conclusions: Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions.展开更多
Background: Familial gigantic melanocytosis (FGM) is a rare disorder first described in 1984 and termed "familial melanopathy with gigantic melanocytes". The cause of the disorder is still unknown. Melanocyt...Background: Familial gigantic melanocytosis (FGM) is a rare disorder first described in 1984 and termed "familial melanopathy with gigantic melanocytes". The cause of the disorder is still unknown. Melanocytes in both hyper- and hypopigmented skin seem to be unable to deliver melanin to the surrounding keratinocytes. Objective: In this study,we report four newcases of FGM. Electronmicroscopic examination was performed in a trial to shed more light on the underlying defect in this disorder. Patients and methods: Patients were examined clinically and biopsies were taken from both hyperpigmented and hypopigmented areas, and divided into two parts; one part was processed for routine microscopic examination with hematoxylin and eosin and Masson Fontana stains. The other portion of the biopsy was fixed in glutraldhyde 3% and processed for electron microscopic (EM) examination. Results: By light microscopy, the patients skin showed areas of hyperpigmented basal cells alternating with poorly pigmented areas. Hair follicles in the scalp biopsies showed the same pathology. By EM, pigmented areas showed gigantic melanocytes and heavily pigmented keratinocytes. Nonpigmented areas showed poorly pigmented keratinocytes and fewer, but also gigantic melanocytes. Conclusions: The raindrop-like hypopigmentation in this disorder can be explained by a failure of melanocytes to deliver melanin to their surrounding keratinocytes. The cause of the presence of heavily pigmented keratinocytes in the hyperpigmented zones could not be determined. There is a strong possibility of a more widespread abnormality affecting not just the melanocytes.展开更多
Two cases of dyschromatosis universalis hereditaria (DUH)-from a Chinese family are presented. Case 1 was a 62-year-old woman who had a generalized and progressive hyper-and hypopigmentation of the skin from the age o...Two cases of dyschromatosis universalis hereditaria (DUH)-from a Chinese family are presented. Case 1 was a 62-year-old woman who had a generalized and progressive hyper-and hypopigmentation of the skin from the age of 8 years. Her brother had also developed a similar skin pigmentary defect from about the same age. Histopathological and ultrastructural examination of lesional skin showed increased melanin content in epidermal keratinocytes but no changes in the appearance or number of melanocytes. Although hereditary defects may influence melanogenesis resulting in a pigmentary anomaly, the pathogenesis of DUH remains unclear.展开更多
文摘Background: The expression of calcium-binding S100 molecules organized within the epidermal differentiation complex on chromosome 1q21 is disturbed in hyperproliferative skin diseases such as psoriasis. Objectives: We studied whether serum levels of S100 proteins A8 (S100A8) and A9 (S100A9) are elevated in psoriasis, correlated their amounts with disease activity and identified potential cellular sources. Methods: Serum obtained from psoriasis patients or from healthy individuals was studied for S100A8 and S100A9 levels by enzyme-linked immunosorbent assay. Data were correlated to disease activity as reflected by the Psoriasis Area and Severity Index (PASI). Cellular sources of S100A8 and S100A9 were identified by in situ hybridization and immunohistochemistry of lesional psoriatic and nonlesional, nonpsoriatic skin. Results: A significant increase of S100A8/S100A9 serum levels was found in patients with psoriasis compared with healthy controls. Grading the patients into two groups of severity, individuals with a PASI of < 15 showed serum levels of 705 ± 120 ng mL- 1 (mean ± SEM, n = 18), those with a PASI of ≥ 15 showed levels of 1315 ± 150 ng mL- 1 (n = 32) while controls presentedwith 365± 50 ng mL- 1. Performing in situ hybridization of lesional psoriatic skin we detected a dramatic induction of both S100A8 and S100A9 mRNA and protein primarily in the suprabasal layers of the epidermis while expression was negligible in nonlesional,nonpsoriatic interfollicular epidermis. Conclusions: Our data demonstrate that hyperproliferation and abnormal differentiation of psoriatic skin is associated with a massive upregulation and secretion of S100A8 and S100A9, suggesting not only a prominent role of these molecules during intracellular calcium-dependent signalling but also implying distinct extracellular functions.
文摘Background: Familial gigantic melanocytosis (FGM) is a rare disorder first described in 1984 and termed "familial melanopathy with gigantic melanocytes". The cause of the disorder is still unknown. Melanocytes in both hyper- and hypopigmented skin seem to be unable to deliver melanin to the surrounding keratinocytes. Objective: In this study,we report four newcases of FGM. Electronmicroscopic examination was performed in a trial to shed more light on the underlying defect in this disorder. Patients and methods: Patients were examined clinically and biopsies were taken from both hyperpigmented and hypopigmented areas, and divided into two parts; one part was processed for routine microscopic examination with hematoxylin and eosin and Masson Fontana stains. The other portion of the biopsy was fixed in glutraldhyde 3% and processed for electron microscopic (EM) examination. Results: By light microscopy, the patients skin showed areas of hyperpigmented basal cells alternating with poorly pigmented areas. Hair follicles in the scalp biopsies showed the same pathology. By EM, pigmented areas showed gigantic melanocytes and heavily pigmented keratinocytes. Nonpigmented areas showed poorly pigmented keratinocytes and fewer, but also gigantic melanocytes. Conclusions: The raindrop-like hypopigmentation in this disorder can be explained by a failure of melanocytes to deliver melanin to their surrounding keratinocytes. The cause of the presence of heavily pigmented keratinocytes in the hyperpigmented zones could not be determined. There is a strong possibility of a more widespread abnormality affecting not just the melanocytes.
文摘Two cases of dyschromatosis universalis hereditaria (DUH)-from a Chinese family are presented. Case 1 was a 62-year-old woman who had a generalized and progressive hyper-and hypopigmentation of the skin from the age of 8 years. Her brother had also developed a similar skin pigmentary defect from about the same age. Histopathological and ultrastructural examination of lesional skin showed increased melanin content in epidermal keratinocytes but no changes in the appearance or number of melanocytes. Although hereditary defects may influence melanogenesis resulting in a pigmentary anomaly, the pathogenesis of DUH remains unclear.
