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Microscopic polyangiitis is a systemic small vessel vasculitis, which often has cutaneous and musculoskeletal features. Microscopic polyangiitis is a member of the family of anti-neutrophil cytoplasmic auto-antibody (ANCA)-associated vasculitides and is strongly associated with anti-myeloperoxidase (MPO)-ANCA. Titres of MPO-ANCA may reflect disease activity and play a pathogenic role. Patients with microscopic polyangiitis usually present with erythematous macules on the extremities as the first cutaneous manifestation. Skin biopsy specimens from the erythema reveal small-sized vessels that are infiltrated with neutrophils, consistent with leukocytoclastic vasculitis, in the deep dermis to the subcutaneous fat tissue. The cutaneous involvement is present at an early stage of microscopic polyangiitis with other non-specific symptoms, such as arthralgias and myalgias. The initial cutaneous manifestations are important in early diagnosis of possible ANCA-associated vasculitides with elevated ANCA titres. [ABSTRACT FROM AUTHOR]

We previously established a mouse neural crest cell line named NCCmelb4, which is positive for Kit and negative for tyrosinase. NCCmelb4 cells were useful to study the effects of extrinsic factors such as retinoic acids and vitamin D3 on melanocyte differentiation, but in order to study the development of melanocytes from multipotent neural crest cells, cell lines of melanocyte progenitors in earlier developmental stages are needed. In the present study, we established an immortal cell line named NCCmelb4M5 that was derived from NCCmelb4 cells. NCCmelb4M5 cells do not express Kit and are immortal and stable in the absence of Kit ligand. They are positive for melanocyte markers such as tyrosinase-related protein 1 and DOPAchrome tautomerase and they contain stage I melanosomes. Interestingly, glial fibrillary acidic protein, which is a marker for glial cells, is also positive in NCCmelb4M5 cells, while NCCmelb4 cells are negative for this protein. Immunostaining and a cell ELISA assay revealed that 12- O-tetradecanoylphorbol 13-acetate (TPA) and cholera toxin (CT) induce Kit expression in NCCmelb4M5 cells. Real-time polymerase chain reaction analysis also demonstrated the induction of Kit mRNA by TPA and CT. Microphthalmia-associated transcription factor mRNA is simultaneously enhanced by the same treatment. Kit induced by TPA/CT in NCCmelb4M5 cells disappeared after the cells were subcultured and incubated without TPA/CT. These findings show that NCCmelb4M5 cells have the potential to differentiate into Kit-positive melanocyte precursors and may be useful to study mechanisms of development and differentiation of melanocytes in mouse neural crest cells. [ABSTRACT FROM AUTHOR]

Certain moisturizers can improve skin barrier function in atopic dermatitis. The effect of topical nicotinamide on atopic dry skin is unknown. We examined the effect of topical nicotinamide on atopic dry skin and compared the results with the effect of white petrolatum in a left–right comparison study.Twenty-eight patients with atopic dermatitis, with symmetrical lesions of dry skin on both forearms, were enrolled, and were instructed to apply nicotinamide cream containing 2% nicotinamide on the left forearm and white petrolatum on the right forearm, twice daily over a 4- or 8-week treatment period. Transepidermal water loss and stratum corneum hydration were measured by instrumental devices. The amount of the stratum corneum exfoliated by tape stripping (desquamation index) was determined by an image analyzer.Nicotinamide significantly decreased transepidermal water loss, but white petrolatum did not show any significant effect. Both nicotinamide and white petrolatum increased stratum corneum hydration, but nicotinamide was significantly more effective than white petrolatum. The desquamation index was positively correlated with stratum corneum hydration at baseline and gradually increased in the nicotinamide group, but not in the white petrolatum group.Nicotinamide cream is a more effective moisturizer than white petrolatum on atopic dry skin, and may be used as a treatment adjunct in atopic dermatitis. [ABSTRACT FROM AUTHOR]

To evaluate the etiologic role of ultraviolet (UV) radiation in acquired dermal melanocytosis (ADM), we investigated the effects of UVA and UVB irradiation on the development and differentiation of melanocytes in primary cultures of mouse neural crest cells (NCC) by counting the numbers of cells positive for KIT (the receptor for stem cell factor) and for the L-3,4-dihydroxyphenylalanine (DOPA) oxidase reaction. No significant differences were found in the number of KIT- or DOPA-positive cells between the UV-irradiated cultures and the non-irradiated cultures. We then examined the effects of UV light on KIT-positive cell lines derived from mouse NCC cultures. Irradiation with UVA but not with UVB inhibited the tyrosinase activity in a tyrosinase-positive cell line (NCCmelan5). Tyrosinase activity in the cells was markedly enhanced by treatment with α-melanocyte-stimulating hormone (α-MSH), but that stimulation was inhibited by UVA or by UVB irradiation. Irradiation with UVA or UVB did not induce tyrosinase activity in a tyrosinase-negative cell line (NCCmelb4). Levels of KIT expression in NCCmelan5 cells and in NCCmelb4 cells were significantly decreased after UV irradiation. Phosphorylation levels of extracellular signal-regulated kinase 1/2 in cells stimulated with stem cell factor were also diminished after UV irradiation. These results suggest that UV irradiation does not stimulate but rather suppresses mouse NCC. Thus if UV irradiation is a causative factor for ADM lesions, it would not act directly on dermal melanocytes but may act in indirect manners, for instance, via the overproduction of melanogenic cytokines such as α-MSH and/or endothelin-1. [ABSTRACT FROM AUTHOR]

The effects of 1,25-dihydroxyvitamin D3 on the differentiation of immature melanocyte precursors were studied. The NCC-/melb4 cell line is an immature melanocyte cell line established from mouse neural crest cells. 1,25-dihydroxyvitamin D3 inhibited the growth of NCC-/melb4 cells at concentrations higher than 10-8 m. That growth inhibition was accompanied by the induction of tyrosinase and a change in L-3,4-dihydroxyphenylalanine reactivity from negative to positive. Electron microscopy demonstrated that melanosomes were in more advanced stages after 1,25-dihydroxyvitamin D3 treatment. In primary cultures of murine neural crest cells, L-3,4-dihydroxyphenylalanine-positive cells were increased after 1,25-dihydroxyvitamin D3 treatment. These findings indicate that 1,25-dihydroxyvitamin D3 stimulates the differentiation of immature melanocyte precursors. Moreover, immunostaining and reverse transcription–polymerase chain reaction analysis revealed that endothelin B receptor expression was induced in NCC-/melb4 cells following treatment with 1,25-dihydroxyvitamin D3 . The induction of endothelin B receptor by 1,25-dihydroxyvitamin D3 was also demonstrated in neural crest cell primary cultures, but not in mature melanocytes. The expression of microphthalmia-associated transcription factor was induced in NCC-/melb4 cells treated with 1,25-dihydroxyvitamin D3 and endothelin 3, but not by 1,25-dihydroxyvitamin D3 alone, suggesting that endothelin 3 may stimulate the expression of the microphthalmia-associated transcription factor gene after binding to the endothelin B receptor induced by 1,25-dihydroxyvitamin D3 . These findings suggest a regulatory role for vitamin D3 in melanocyte development and melanogenesis, and may also explain the working mechanism of vitamin D3 in the treatment of vitiligo. [ABSTRACT FROM AUTHOR]

Recent studies have shown increased T-helper (Th) 2 cytokine expression and decreased IFN-γ expression in peripheral blood from patients with atopic dermatitis (AD). In the present study, we examined the cytokine expression in peripheral blood mononuclear cells in patients with AD and tested how the cytokine profile correlated with the patients’ age, severity and laboratory findings. Peripheral blood mononuclear cells obtained from 20 patients with AD were stimulated with phorbol 12-myristate 13-acetate and ionomycin, and were examined for the frequencies of CD4+ cells expressing IL-4, IL-13 and IFN-γ at the single cell level using intracellular cytokine staining and flow cytometry. There was a significant positive correlation between IL-4 and IL-13 expression in CD4+ cells. Expression levels of both IL-4 and IL-13 in CD4+ cells were significantly correlated with peripheral blood eosinophilia. These findings suggest that CD4+ cells producing IL-4 and IL-13 play important roles in the pathogenesis of AD. IFN-γ expression did not correlate with either IL-4 or IL-13 expression, or with blood eosinophilia. We also measured serum levels of IL-13 in 144 patients with AD using enzyme-linked immunosorbent assay, and found 16 patients with detectable levels of serum IL-13. IL-13+ patients had significantly higher serum IgE levels than IL-13− patients, suggesting a direct association between serum levels of IL-13 and IgE. It was also shown that the IL-13+ group was significantly younger in age than the IL-13− group, although the implication of this finding is not clear at present. The sum of these findings suggested that the predominance of Th2 cells and the consequent overexpression of IL-4 and IL-13 in peripheral blood may be deeply involved in the pathogenetic process of AD. [Copyright &y& Elsevier]

Stem cell factor is essential to the migration and differentiation of melanocytes during embryogenesis based on the observation that mutations in either the stem cell factor gene, or its ligand, KIT, result in defects in coat pigmentation in mice. Stem cell factor is also required for the survival of melanocyte precursors while they are migrating towards the skin. Transforming growth factor β1 has been implicated in the regulation of both cellular proliferation and differentiation. NCC-melb4, an immortal cloned cell line, was cloned from a mouse neural crest cell. NCC-melb4 cells provide a model to study the specific stage of differentiation and proliferation of melanocytes. They also express KIT as a melanoblast marker. Using the NCC-melb4 cell line, we investigated the effect of transforming growth factor β1 on the differentiation and proliferation of immature melanocyte precursors. Immunohistochemically, NCC-melb4 cells showed transforming growth factor β1 expression. The anti-transforming growth factor β1 antibody inhibited the cell growth, and downregulated the KIT protein and mRNA expression. To investigate further the activation of autocrine transforming growth factor β1, NCC-melb4 cells were incubated in nonexogenous transforming growth factor β1 culture medium. KIT protein decreased with anti-transforming growth factor β1 antibody concentration in a concentration-dependent manner. We concluded that in NCC-melb4 cells, transforming growth factor β1 promotes melanocyte precursor proliferation in autocrine and/or paracrine regulation. We further investigated the influence of transforming growth factor β1 in vitro using a neural crest cell primary culture system from wild-type mice. Anti-transforming growth factor β1 antibody decreased the number of KIT positive neural crest cell. In addition, the anti-transforming growth factor β1 antibody supplied within the wild-type neural crest explants abolished... [ABSTRACT FROM AUTHOR]

The effects of all-trans retinoic acid on the differentiation and proliferation of immature melanocyte precursors were studied. NCC-melb4 cells are an immortal cloned cell line established from mouse neural crest cells using a single-cell cloning method. These cells were positive for tyrosinase-related protein 1, tyrosinase-related protein 2 and KIT, but were negative for tyrosinase and had no dihydroxyphenylalanine reaction. They contained only stage I melanosomes without any melanosomes in more advanced stages. After treatment with all-trans retinoic acid, many of the cells became tyrosinase- and dihydroxyphenylalanine-reaction-positive, changed from polygonal to dendritic in shape, and had stage III to IV melanosomes. These findings indicate that treatment with all-trans retinoic acid induced the differentiation of NCC-melb4 cells. Reverse transcription polymerase chain reaction analysis revealed a marked increase in expression of microphthalmia-associated transcription factor mRNA after all-trans retinoic acid treatment, suggesting that microphthalmia-associated transcription factor may be the key molecule in this event. Enhanced expression of protein kinase Cα following treatment with all-trans retinoic acid was also demonstrated. The proliferation of NCC-melb4 cells was inhibited by all-trans retinoic acid in a dose-dependent manner. Increased apoptosis after all-trans retinoic acid treatment was observed by electron microscopy, the TUNEL method, DNA fragmentation assay, and flow cytometry. All-trans retinoic acid upregulated caspase-3 and downregulated bcl-2. Electron microscopy showed that apoptotic cells contained melanosomes of advanced stages, suggesting that mature melanocytes may tend to undergo apoptosis after all-trans retinoic acid treatment. This study provides important clues towards understanding the roles and working mechanisms of retinoic acids in melanocyte development and melanogenesis. [ABSTRACT FROM AUTHOR]

Abstract Background The role of transforming growth factor-β (TGF-β) in carcinogenesis is complex, with some reports indicating a tumor inhibition role and others indicating a tumor promotion role. In particular, TGF-β3 is thought to play a key role in controlling epithelial homeostasis. Immunopositive p53 has been demonstrated in a variety of human malignant tumors and its role in oncogenesis and tumor progression is thought to be important. Extramammary Paget's disease (EPD) and Bowen's disease are skin cancers of unknown histogenesis. Objective To clarify the role of TGF-β3 and p53 in EPD and Bowen's disease and to better understand the origin of these disorders. Methods Specimens were obtained from 12 patients with EPD and 12 patients with Bowen's disease seen at our clinic between 1993 and 2000. TGF-β3 and p53 immunohistochemical staining was performed. Results In three of the 12 EPD patients and five of the 12 Bowen's disease patients, positive p53 staining was detected. In contrast, TGF-β3 overexpression was detected in all EPD patients, whereas downregulated TGF-β3 expression was detected in all Bowen's disease patients. Conclusions The present data suggest different roles for TGF-β3 in abnormal epidermal cells in EPD and Bowen's disease. Thus, TGF-β3 expression may be modulated differently via a p53-dependent or -independent pathway in the pathogenesis of EPD and Bowen's disease. Moreover, high TGF-β expression appears to be a useful indicator of tumor activity in EPD. [ABSTRACT FROM AUTHOR]

This article presents a case of thromboangiitis obliterans associated with peripheral blood and eosinophilic cellulitis-like skin lesions. A 20-year-old Japanese man was admitted with a 1-month history of fingertip necrosis. He had painful skin ulcers at the periphery of the right index finger, right middle finger and left middle finger. He had bronchial asthma in childhood. He had smoked two packs of cigarettes per day for 5 years. An angiogram of the extremities showed multiple occlusions of the bilateral ulnar and left radial arteries.

We have previously shown that frontoparietal scleroderma en coup de sabre, a type of linear scleroderma that affects the face and scalp, follows the lines of Blaschko, but the question whether linear scleroderma that occurs in the limbs follows Blaschko's lines has not been answered. We describe the case of a 4-year-old girl with multiple morphea showing remarkable unilateral systematized distribution and whose linear lesions in the limbs appeared to follow Blaschko's lines. We suggest that linear scleroderma of the limbs, as well as frontoparietal scleroderma, may occur along the lines of Blaschko. Since both the unilateral distribution and the lesions along Blaschko's lines are the patterns created by genetic mosaicism, we suggest that a significant part of linear scleroderma and perhaps a smaller part of multiple morphea could be related to cutaneous mosaicism. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented related to a case study on the use of mizoribine in treatment of sarcoidosis and cutaneous vasculitis.

A letter to the editor is presented citing research findings from a case of adult T-cell lymphoma/leukemia developing in a psoriasis patient treated with long-term cyclosporine.

A letter to the editor about a case of a 42-year-old man who was presented with Churg-Strauss syndrome with cutaneous and neurological manifestations preceeding asthma is presented.

Objectives. Recent research suggests that lysosomal-associated membrane protein-2 (LAMP-2) could be one of the target antigens in the pathogenesis of vasculitides. We established a transgenic rat model, env-pX rats, with various vasculitides including cutaneous vasculitis. Human primary cutaneous vasculitis includes cutaneous polyarteritis nodosa (CPN) and Henoch–Schönlein purpura (HSP). We measured serum anti-LAMP-2 antibody levels in morbid env-pX rats and injected anti-LAMP-2 antibody into premorbid env-pX rats. We further measured serum anti-LAMP-2 antibody levels in patients with CPN and HSP.Methods. Cutaneous vasculitis was observed in ∼30% of 6-month-old morbid env-pX rats. In contrast, these findings were rare in premorbid env-pX rats under 3 months old. We also examined 85 patients with CPN and 36 adult patients with HSP. Serum anti-LAMP-2 antibody levels were determined using ELISA. Premorbid env-pX rats under 3 months old were given an i.v. injection of anti-LAMP-2 antibody at day 0 and day 7. At day 14, these rats underwent histopathological and direct immunofluorescence examination. Cell surface LAMP-2 expression of rat neutrophils was examined by flow cytometry.Results. Serum anti-LAMP-2 antibody levels were significantly higher in morbid env-pX rats than in wild-type normal rats. In addition, the levels in the cutaneous vasculitis group of morbid env-pX rats were significantly higher than the no cutaneous vasculitis group. Intravenous anti-LAMP-2 antibody injection into premorbid env-pX rats under 3 months old induced infiltration of neutrophils into cutaneous small vessels. Anti-LAMP-2 antibody-binding neutrophils were detected there. LAMP-2 expression on the cell surface of neutrophils in premorbid env-pX rats under PMA stimulation was higher compared with controls. Serum anti-LAMP-2 antibody levels in CPN and HSP were significantly higher than those of healthy controls.Conclusion. These data support a positive relationship between anti-LAMP-2 antibody and cutaneous vasculitis. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis (AD) is an allergic skin disease that follows a clinical course of ‘flare-up’ and remission. Histamine and tryptase are inducers of pruritus and non-sedating second-generation antihistamines, including fexofenadine, are widely used for treatment of allergic skin disorders. Objective: We assessed the efficacy of a second-generation antihistamine in AD patients and examined its pharmacological effects on chemical mediators. Methods: The scoring atopic dermatitis (SCORAD) instrument and visual analogue scale (VAS) for pruritus were used to assess disease severity in 349 AD patients. Twenty patients with moderate AD symptoms, who had not received any treatment for 2 weeks, were randomly assigned into two groups. Ten patients underwent fexofenadine and emollient treatment (Group 1) and 10 received fexofenadine and steroid treatment (Group 2) for 1 week. SCORAD and VAS for pruritus, and blood histamine and tryptase levels were evaluated before and after treatment. Results: SCORAD and VAS improved in both Group 1 (p =0.01 and p =0.006, respectively) and Group 2 (p <0.001 and p =0.001, respectively). The improvement in Group 1 showed a significant correlation with the diminution rate of blood tryptase levels (SCORAD: r =0.83 and p =0.013, respectively; VAS: r =0.81, p =0.015, respectively). End-point plasma tryptase levels were significantly lower than baseline levels in Group 2 (p =0.046). Histamine levels did not show any significant changes in either group. Conclusion: These results suggest that second-generation antihistamine therapy reduces AD pruritus, resulting in the effective clinical treatment for AD. In addition, monitoring tryptase levels during antihistamine therapy in moderate AD treatment may prove to be useful in establishing treatment effects. [Copyright &y& Elsevier]

Summary: Background:: Our previous study showed that T cells in skin lesions of human atopic dermatitis (AD) had oligoclonal accumulation, indicating the involvement of antigen-specific immune reactions at those sites. Recently, NC/Nga mice, which develop skin lesions similar to AD, have been proposed as a model for that disease. Objective:: To clarify whether NC/Nga mice are suitable as a model for human AD from the viewpoint of their antigen-specific immune responses. Methods:: Reverse transcription-polymerase chain reaction (RT-PCR) and single strand conformation polymorphism (SSCP) analyses were conducted to detect TCR BV genes of clonally expanded T cells derived from NC/Nga mice at an early phase of the AD-like dermatitis, at a late phase of the dermatitis, and with no AD-like dermatitis. Results:: (1) T cells with TCR BV 7, 10 and 17 reside in the skin of NC/Nga mice without the AD-like dermatitis. (2) T cells with these BV genes contain oligoclonal accumulations, however, expanded T cell clonotypes are also detected in the spleen and exist constantly during the course of the AD-like dermatitis. (3) Development of the AD-like dermatitis is associated with additional oligoclonal expansion/accumulation of T cells with TCR BV 2, 4 and 6 genes. (4) Progression of the AD-like dermatitis is associated with further oligoclonal expansion/accumulation of T cells with the TCR BV 14 gene. (5) Some of the expanded TCR clonotypes are common between the individual mice and between early and late phases. Conclusions:: Taking these data together with the previous human AD studies, NC/Nga mice seem to be an appropriate model for human AD. [Copyright &y& Elsevier]

The article presents a case study of a 56-year-old Japanese woman who had been diagnosed with low-grade papillary serous carcinoma of the ovary. The woman had undergone a total abdominal hysterectomy and seven chemotherapy courses. A computed tomography (CT) of her abdomen and pelvis revealed metastatic lesions, which were biopsied and found to be ovarian cancer.

The article presents several case studies related to elevated levels of serum Immunoglobulin M anti-phosphatidylserineprothrombin complex antibodies in patients with cancer associated vasculitis. It mentions association between antiphospholipid and cancer leads to the segregation of phosphatidylserine to the internal leaflet of the plasma membrane in vascular endothelial cell.

Background Psoriasis is a refractory inflammatory disease, however, its pathophysiology is still not fully understood. Objective We tried to identify novel serum peptides associated with the pathophysiology of psoriasis. Methods Serum peptides from 24 patients with psoriasis vulgaris (PV), 10 patients with psoriatic arthritis (PsA), 14 patients with atopic dermatitis (AD), and 23 healthy control (HC) subjects were analyzed by mass spectrometry. The effects of some peptides on the secretion of humoral factors from dermal cells were investigated by cytokine arrays and ELISAs. Results A total of 93 peptides were detected. 24, 20, 23, and 2 peptides showed at least 1.2-fold difference in ion intensity between the psoriasis (PV + PsA) and HC groups, between the PV + PsA and AD groups, between the PV and PsA groups, and between patients with severe-to-moderate PV ( n = 6) and those with mild PV ( n = 18), respectively ( p < 0.05). 13 out of 27 peptides that showed at least 1.5-fold ion intensity difference in the abovementioned 4 comparisons were identified. The parent proteins of the identified peptides included a coagulation factor, proteins involved in the maintenance of skin, and a protein relating to cytoskeleton. We focused on 2 peptides that were increased in the PV + PsA group: a fibrinogen α chain-derived peptide (1462 m / z ), the unmodified form of which was fibrinopeptide A-des-alanine (FPAdA), and a filaggrin (FLG)-derived peptide (1977 m / z ), a modified form of FLG 2099–2118 (Q 2099 pE, Q 2115 E; FLG-pEE). FPAdA stimulation increased the secretion of GROα from dermal microvascular endothelial cells (dMVECs) and decreased the secretion of lipocalin-2 from keratinocytes in comparison to FPAdA-resequenced peptide stimulation (GROα, 280.9 ± 7.3 pg/mL vs. 229.6 ± 5.0 pg/mL, p < 0.001; lipocalin-2, 273 ± 13 pg/mL vs. 350 ± 10 pg/mL, p < 0.01). Interestingly, FLG-pEE stimulation decreased the secretion of GROα, IL-8, and MCP-1 from dMVECs in comparison to FLG-derived control peptide stimulation (GROα, 844.3 ± 47.5 pg/mL vs. 1038.5 ± 96.9 pg/mL, p < 0.05; IL-8, 2240.1 ± 172.6 pg/mL vs. 3221.8 ± 523.7 pg/mL, p < 0.05; MCP-1, 4057.8 ± 157.2 pg/mL vs. 4619.1 ± 213.4 pg/mL, p < 0.05). Conclusions The results suggested that some serum peptides are involved in the pathophysiology of psoriasis, regulating the secretion of inflammatory chemokines and an antimicrobial protein. The modulation of serum peptides may be a potential therapeutic strategy for psoriasis. [ABSTRACT FROM AUTHOR]

The article presents a case study of an 88-year-old woman with non Hodgkin's lymphoma (NHL) who underwent a surgery for the excision of mass from her breast. After skin biopsy, she was diagnosed with homogenous, eosinophillic nodular deposit of amyloid in the dermis in association with blood vessels. A partial response of treatment with psoralen plus ultraviolet-A (PUVA) therapy was seen in the women.

The article presents a case study of a 19-year-old Japanese man who has a history of skin ulceration on his head. The patient manifested bowel paon and bloody diarrhea for 4 weeks. The patient's laboratory results revealed leukocytosis and elevated C-reactive protein levels. It indicates that the patient was diagnosed of having pyoderma gangrenosum and ulcerative colitis due to decreased interleukin- 6, interleukin-8, and anti-phosphatidylserine-prothrombin complex antibody.

The article reports on the cutaneous lymphomas which is divided by World Health Organization-European Organization for Research and Treatment of Cancer (WHO-EORTC) into three chief class, leg type (PCLBCL-LT), cutaneous diffuse large B-cell lymphoma and cutaneous follicular centre lymphoma. It states a case of a man who has HIV in relation with leg type. It mentions that leg type has a fast development of tumour masses on the leg. It says that person who has HIV has higher lymphoma non-Hodgkin.

The article presents a case study for a 38-year-old Japanese with a great growth of fatty accumulations in the neck, upper trunk, and upper extremities. It notes that the patient had a medical history of atopic dermatitis (AD). A diffuse proliferation of normal adipose tissue in the subcutaneous fat was found through histological examination of a skin biopsy. However, in radioallergosorbent test (RAST), the patient was seen with five aeroallergens.

The article presents a case study of a 22-year-old Japanese woman with non-palpable pigmented patches with interspersed discrete brown macules. It notes that the patient had no history of abnormal cutaneous pigmentation. Multiple, discrete, and coalescing macules were found in the physical examination. It states that the patient was considered healthy because of the absence of pigmentation of the mucosa in the patient's eye or mouth.

A letter to the editor is presented concerning chronic myeloid leukaemia (CMV) as a clonal myeloproliferative disorder, where the Philadelphia chromosome is the hallmark of cytogene.

Lysosomal-associated membrane protein-2 (LAMP-2) is a target antigen for anti-neutrophil cytoplasmic anti-bodies (ANCAs), which are closely linked to a subset of primary systemic vasculitides. Cutaneous polyarteritis nodosa (CPN) is a necrotizing vasculitis of small to medium-sized arteries within the skin. We measured levels of serum anti-LAMP-2 antibody in 50 patients with CPN, 8 with microscopic polyangiitis (MPA), and 34 healthy persons. We also investigated the presence of ANCA in patients with CPN using indirect immunofluorescence 0IF), a direct ELISA and a capture ELISA specific for myeloperoxidase (MPO) and proteinase 3 (PR3). Serum anti-LAMP-2 antibody levels differed significantly between patients with CPN (0.263 U/ml) and those with MPA (0.180 U/ml) (p = 0.0102). Serum of all patients with CPN was negative for MPO-ANCA and PR3-ANCA by both direct ELISA and capture ELISA. In contrast, IIF assay revealed ANCA in 42 (84.0%) of the 50 CPN patients. Serum anti-LAMP-2 antibody levels in the perinuclear ANCA (P-ANCA) group were significantly elevated compared with the non-ANCA group (p=0.0147). We suggest that anti-LAMP-2 antibody could play an important role in the pathogenesis of CPN in the presence of P-ANCA detected by IIF. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 59-year-old man, who developed asthma and reported painful purpuric skin lesions on lower limbs and soles. It mentions that no signs of necrotizing vasculitis was noticed in the patient upon microscopic examination of the skin biopsy specimen obtained from the plaque. It mentions that skin biopsies revealed histopathological necrotizing vasculitis.

Summary: Background: In congenital or acquired dermal melanocytosis, attachment of melanocyte with elastic fiber was shown in electron microscopy of unknown biological meaning. We hypothesize elastin-derived peptide may play a role in activating dermal melanocyte precursors. Objectives: This study was designed to determine: (i) whether melanocyte precursors express elastin binding protein (EBP); (ii) ontogenic expression of EBP and elastin in murine embryonic skin; (iii) the effects of elastin-derived peptide (VGVAPG) on melanocyte precursors. Methods: Using immunohistochemistry or Western blot to identify EBP on murine embryonic sections, neural crest cell (NCC) primary culture explants, or two melanocyte precursor cell lines, NCCmelb4 and NCCmelan5. NCC explants or cells were treated with VGVAPG to compare its effect on proliferation, dendrite formation, melanosome maturation and tyrosinase mRNA expression of melanocyte precursors. Results: EBP was immunostained on c-kit+ melanocyte precursors. 67kDa EBP protein was immunoblotted on NCCmelb4 and NCCmelan5 cells. EBP was expressed early at embryonic day (E) 9.5, but elastin appeared later at E12.5 skin. VGVAPG increased DOPA-positive cell number and enhanced their dendrite formation in NCC explants. Electron microscopy showed advanced melanosome maturation in NCC explants or cells treated with VGVAPG. VGVAPG enhanced tyrosinase mRNA expression in NCCmelan5 cells. Conclusions: Melanocyte precursors expressed EBP. VGVAPG stimulated their melanogenesis and dendrite formation. In the developmental journey interaction between elastin and EBP-expressed melanocyte precursors in embryos happened mainly since the stage of tertiary melanoblasts. These findings first provide biological evidences for the interaction between melanocyte and elastic fiber. [Copyright &y& Elsevier]

Genes encoding Kit and the Kit ligand (KL) play essential roles in the differentiation of melanoblasts. We previously established three immortal but distinct cell populations of mouse neural crest (NC) cells. NCCmelb4M5 cells do not express Kit and grow independently of KL; they have the potential to differentiate into NCCmelb4 cells, which are Kit-positive melanocyte precursors. NCCmelan5 cells show the characteristics of differentiated melanocytes. All three cell lines demonstrated bone morphogenetic protein (BMP) receptor expression. BMP-4 upregulated Kit protein and mRNA expression in most immature NCCmelb4M5 cells. Noggin, a BMP-4 antagonist, dramatically decreased the Kit expression induced by BMP-4. Western blot analysis revealed that extrinsic BMP-4 leads to the phosphorylation of Smads in NCCmelb4M5 cells. Using transfected Kit-promoter reporter, we showed BMP-4 could activate Kit promoter in transfected NCCmelb4M5 cells. We conclude that BMP-4 is active and is involved in the regulation of Kit expression on most immature melanocyte precursors. We further investigated the influence of BMP-4 in vitro using primary NC cells cultured from wild-type mice. Addition of BMP-4 to the medium increased the number of Kit-positive cells compared to diluent-treated controls. We have identified BMP-4 as an important factor for prenatal Kit-negative melanoblasts just prior to entering the Kit-dependent cycle of melanogenesis.Journal of Investigative Dermatology (2008) 128, 1220–1226; doi:10.1038/sj.jid.5701136; published online 25 October 2007 [ABSTRACT FROM AUTHOR]

The article reports on a study which determined a possible correlation of antiphospholipid (aPL) antibodies with adult Henoch-Schonlein purpura (HSP) and cutaneous leukocytoclastic angiitis (CLA). The author reviewed records of 30 HSP and 8 CLA patients between 2003 and 2007. The records indicated that 22 HSP patients, or 73 percent, had serum anticardiolipin (aCL) antibodies, which the article says, closely relates to vasculitis or CLA.

Summary: Background: We have established two immature melanocyte cell lines from murine neural crest cells. NCC-E3 cells have Stage II melanosomes and express tyrosinase while in NCCmelb4 cells, the melanosomes remain at Stage I and tyrosinase is not expressed. These cell lines may be useful in studying the differentiation of melanocyte precursors. Objective: To perform proteomic analysis of the two cell lines to identify proteins related to and possibly responsible for their different maturation stages. Methods: Western blotting, two-dimensional differential image gel electrophoresis (2D-DIGE), liquid chromatography–tandem mass spectrometry (LC–MS/MS), real-time PCR analysis and RNA interference using siRNA were employed in this study. Results: Western blotting revealed that the processed form of gp100, which is specific for Stage II melanosomes, is expressed in NCC-E3 cells but not in NCCmelb4 cells. 2D-DIGE identified two protein spots showing 4.06- and 2.22-fold increases in NCC-E3 cells compared to NCCmelb4 cells. Analysis of those proteins by LC–MS/MS revealed that the former was calreticulin and the latter was BiP/GRP78. When calreticulin mRNA expression in NCC-E3 cells was blocked by siRNA, tyrosinase protein was abolished and DOPA-reactivity was decreased, although tyrosinase mRNA was abundantly expressed after the same treatment. Conclusion: Calreticulin, a lectin chaperone, is an essential molecule for the processing of tyrosinase in murine melanocytes. The role of molecular chaperones such as calreticulin should be considered when analyzing the mechanism(s) of melanocyte differentiation. [Copyright &y& Elsevier]

Summary: Background: Blood platelets store sphingosine 1-phosphate (S1P) abundantly and release this bioactive lipid extracellularly. S1P acts as an intercellular mediator through interaction with the endothelial differentiation gene (EDG)/S1P family of G protein-coupled receptors. Of the EDG family S1P receptors, EDG-5 (S1P2) is inhibited in migration induced by S1P. Diabetes impairs numerous aspects of tissue repair. Failure of wound angiogenesis is known to delay diabetic wound healing. Objectives: We examined whether S1P subcutaneous injection could improve the healing of full-thickness skin wounds in healthy and diabetic mice. We further determine if the combined S1P and EDG-5 (S1P2) antagonist injection in diabetic mice could affect wound healing. Finally, we examined the histopathological findings of the wound following S1P injection in diabetic mice. Methods: Eight- to 10-week-old BALA/c mice, diabetic db/db mice and Wister rats were used for the studies. A full-thickness wound was made on the dorsal skin of the healthy and diabetic mice. Either 10μM or 100μM of S1P or vehicle control (BSA/PBS) was injected into the wound bed every day. We calculated the wound area after each injection. EDG-5 (S1P2) antagonist (JTE-013) or vehicle (DMSO) was then injected in addition to the S1P around the dorsal wound of diabetic mice and the wound diameter was measured. Wound tissue samples were excised following injection for histopathological examination. Results: Wound area in normal BALA/c mice did not significantly decrease upon S1P injection compared to S1P-untreated controls. S1P injection alone showed significant promotion of wound healing in diabetic mice compared to no S1P treatment. The combination of S1P and EDG-5 (S1P2) receptor antagonist administration induced maximal wound healing in diabetic mice. Histopathological examination revealed that S1P induces neo-vascularization potential in rats and diabetic mice wound. Conclusions: S1P injection in diabetic mice significantly accelerated cutaneous wound healing in the neo-vascularization process. The results demonstrate that S1P affects and sustains all key cellular processes responsible for wound repair and point to a unique potential for this molecule in the therapy of diabetic wounds, particularly as an angiogenic agent in treatment of diabetic wounds. [Copyright &y& Elsevier]

Abstract: The murine recessive yellow (Mc1r e ) is a loss-of-function mutation in the receptor for α-melanocyte-stimulating hormone, melanocortin receptor 1 (Mc1r) and produces yellow coats by inducing pheomelanin synthesis in hair follicular melanocytes. However, it is not known whether the Mc1r e mutation affects the proliferation and differentiation of melanocytes. In this study, the proliferation and differentiation of recessive yellow epidermal melanocytes cultured in dibutyryl cyclic AMP-supplemented serum-free medium were investigated in detail. The melanocytes produced mainly eumelanin in this culture system. The proliferation of recessive yellow melanocytes was decreased compared with that of wild-type at the e-locus, black melanocytes. The differentiation of melanocytes was also delayed and inhibited in recessive yellow mice. Tyrosinase (TYR) activity and TYR-related protein 1 (TRP1) and TRP2 (dopachrome tautomerase, DCT) expressions were decreased and, in addition, the maturation of stage IV melanosomes was inhibited. Excess l-tyrosine (l-Tyr) added to the culture media rescued the reduced activity of proliferation of melanocytes. l-Tyr also stimulated TYR activity and TRP1 and TRP2 expressions as well as the maturation of stage IV melanosomes and pigmentation. These results suggest that the Mc1r e mutation affects the proliferation and differentiation of melanocytes and l-Tyr rescues the reduced proliferative and differentiative activities by stimulating TYR activity and TRP1 and TRP2 expressions as well as melanosome maturation. [Copyright &y& Elsevier]

Abstract: The slaty (Dct slt ) mutation is known to reduce the activity of dopachrome tautomerase (DCT) in melanocytes. However, it is unknown whether the reduced DCT activity leads to a defect in the proliferation and differentiation of mouse melanocytes. To address this point, the proliferation and differentiation of neonatal melanocytes from Dct slt /Dct slt congenic mice in serum-free primary culture were investigated in detail. The proliferation of slaty epidermal melanoblasts/melanocytes in culture did not differ from that of wild-type mice. However, the differentiation was greatly inhibited. Tyrosinase (TYR) activity detected by dopa reaction as well as staining of DCT in slaty melanocytes was greatly reduced. The content of eumelanin in cultured slaty melanocytes was reduced, whereas the content of pheomelanin in media derived from cultured 7.5-day-old slaty melanocytes was greatly increased. The contents of eumelanin and pheomelanin in the neonatal slaty epidermis and dermis were reduced, except that the pheomelanin content in 3.5-day-old dermis was increased. These results suggest that the slaty mutation affects both eumelanin and pheomelanin synthesis in developmental stage-specific and skin site-specific manners, and, in addition, the gene controls the differentiation of melanocytes via the regulation of activity of TYR in addition to its own DCT. [Copyright &y& Elsevier]

Stem cell factor (SCF) and its receptor, KIT, are essential to the migration and differentiation of melanocytes during embryogenesis. We previously demonstrated that apoptosis is induced by blocking survival function of the SCF/KIT interaction in a mouse neural crest cell (NCC) primary culture. Using the NCCmelb4 cell line, we investigated the occurrence of apoptosis in the cultured cells when KIT receptors were blocked by the monoclonal anti-KIT antibody (ACK2). Apoptosis following treatment with ACK2 was detected by DNA fragmentation assay,in situapoptosis detection, and electron microscopy. We noted a decrease in extracellular signal-related kinase (ERK) and ribosomal S6 kinase (RSK) protein expression following ACK2 incubation. Western blot analysis and real-time quantitative RT-PCR revealed an apparent time-dependent reduction in Bcl-2 protein levels with respect to ACK2 within the NCCmelb4 cells. In terms of Bax expression, a difference was not found. Fas and caspase8 proteins increased time-dependently in proportion to ACK2 incubation. We noted apoptotic cell death upon addition of ACK2, with evidence of possible involvement of Bcl-2 and Fas in the induction of apoptosis. In contrast, no significant correlation between Fas ligand (Fas-L) expression and ACK2 was found. Fas activation appears to occur independent of Fas-L during ACK2-induced cell death. Therefore, we propose that Fas-L expression in NCCmelb4 cells does not play a major role in facilitating apoptosis. Furthermore, we hypothesize that these molecules combined with SCF/KIT play an important role in regulating the induction of vertebrate NCC apoptosis during embryogenesis. [ABSTRACT FROM AUTHOR]

We devised a unique new single-cell cloning method which uses microscope cover glasses and established a melanoblast cell line derived from mouse neural crest cells. A microscope cover glass was nicked and broken into small pieces and put on a dish. Culture medium and a suspension of 20–30 cells/ml were dropped in the dish. After 1–3 d, a piece of glass to which only one cell was adhered was picked up and transferred to another dish containing culture medium. The greatest advantage of this method is that the derivation of a colony from a single cell can be directly confirmed by microscopy and there is no risk of migratory cells being contaminated by other colonies. Using this single-cell cloning method, in this study we established a cell line derived from a neural crest cell line (NCC-S4.1) and designated it as NCCmelb4. When the culture medium was supplemented with stem cell factor (SCF) alone, NCCmelb4 cells were KIT-positive and tyrosinase-negative melanocyte precursors; they remained at an immature and undifferentiated stage. When the medium was supplemented with phorbol 12-o-tetradecanoyl-13-acetate (TPA) + cholera toxin (CT), the cell morphology changed and becamel-3,4-dihydroxyphenylalanine (DOPA)-positive. This observation indicates that the NCCmelb4 cells are capable of further differentiation with suitable stimulation. NCCmelb4 cells derived from the mouse neural crest has characteristics of melanocyte precursors (melanoblasts), and is a cell line which can be utilized to study differentiation-inducing factors and growth factors without the effects of feeder cells. [ABSTRACT FROM AUTHOR]

Background: Atopic dermatitis (AD) is a common chronic inflammatory and allergic skin disease that almost always begins in childhood and follows a course of remittance and flare-up. AD is characterized by intense pruritus and itchiness that can be triggered by an interplay of genetic, immunologic and environmental factors. Of the mediators, histamine is one of the most potent inducers of pruritus. Serum tryptase, which is also a mediator, may be used to examine allergic disease as well. The development of minimal sedation H1 antihistamines (second-generation antihistamines) has revolutionized treatment of allergic diseases. Objective: The present study examines the efficacy of second-generation antihistamines in relieving pruritus due to AD. In addition, the relationship between AD pruritus and antihistamine therapy was analyzed by measuring the blood histamine and tryptase levels. Methods: Thirty-two AD patients were recruited and underwent second-generation antihistamine therapy for 2 weeks. Seventeen received combined topical corticosteroid treatment (Group 1) and the other 15 did not receive steroid treatment (Group 2). The Severity Index and Pruritus Score were assessed as an AD clinical activity index and compared with baseline data. Results: Both the Severity Index and Pruritus Score improved significantly in Group 1 (P<0.001, P<0.05). Group 2 demonstrated a significant improvement in Pruritus Score (P<0.05), but not in the Severity Index. Plasma histamine levels were significantly higher in AD at baseline compared with healthy controls. Conclusion: Following antihistamine therapy, these levels decreased significantly in both AD groups (P<0.05). There was a significant correlation between baseline blood histamine and typtase levels. However, this correlation was not evident following treatment. This may reflect insufficient detection capabilities of the measuring assay. The present results suggest that second-generation antihistamine therapy provides an effective clinical treatment for AD, with a notable improvement in pruritus. Furthermore, antihistamine therapy reduced plasma histamine levels in AD patients. These findings further suggest that high blood histamine and tryptase levels in AD patients contribute to the pathogenesis of this disorder, including the onset of pruritus. [Copyright &y& Elsevier]

Stem cell factor (SCF) is essential to the migration and differentiation of melanocytes during embryogenesis because mutations in either the SCF gene, or its ligand, KIT, result in defects in coat pigmentation in mice. Using a neural crest cell (NCC) primary culture system from wild-type mice, we previously demonstrated that KIT-positive and/or L-3, 4-dihydroxyphenylalanine (DOPA)-positive melanocyte precursors proliferate following the addition of SCF to the culture medium. Extracellular matrix (ECM) proteins are considered to play a role in the migration and differentiation of various cells including melanocytes. We cultured mouse NCCs in the presence of SCF in individual wells coated with ECM; fibronectin (FN), collagen I (CLI), chondroitin sulphate, or dermatan sulphate. More KIT-positive cells and DOPA-positive cells were detected in the presence of SCF on ECM-coated wells than on non-coated wells. A statistically significant increase in DOPA-positive cells was evident in FN and CLI wells. In contrast, in the absence of SCF, few DOPA-positive cells and KIT-positive cells were detected on either the ECM-coated or non-coated wells. We concluded that ECM affect melanocyte proliferation and development in the presence of SCF. To determine the key site of FN function, RGDS peptides in the FN sequence, which supports spreading of NCCs, were added to the NCC culture. The number of DOPA-positive cells decreased with RGDS concentration in a dose-dependent fashion. Immunohistochemical staining revealed the presence of integrin a5, a receptor of RGDS, in NCCs. These results suggest the RGDS domain of FN plays a contributory role as an active site in the induction of FN function in NCCs. In addition, we examined the effect of FN with SCF on the NCC migration by measuring cluster size, and found an increase in size following treatment with FN. [ABSTRACT FROM AUTHOR]

Discusses the establishment and characterization of a mouse neural crest derived cell line, NCCmelan5. Information on skin melanocytes; Materials and methods; Results and discussion.

The article discusses the complete resolution of refractory cutaneous arteritis by intravenous cyclophosphamide pulse therapy in a 76-year-old man presented with a six-month history of recurrent, purpuric macules on his legs. Topics covered include how cyclophosphamide lowers the immune system's response to various diseases and the strong evidence in favor of using cyclophosphamide and corticosteroid to induce remission in systemic vasculitis.

The article presents a case study of a 72-year-old man with a 4-month history of skin lesions having gait disturbances and myalgias. Microscopic examination of the left leg's lower extremity eruption showed nuclear dust, fibrinoid degeneration, erythrocyte extravasation and neutrophilic infiltration. There was a remarkable decline in cutaneous eruptions accompanied by a decrease in swelling and joint pain.