RESUMEN
The Hayabusa2 spacecraft investigated the small asteroid Ryugu, which has a rubble-pile structure. We describe an impact experiment on Ryugu using Hayabusa2's Small Carry-on Impactor. The impact produced an artificial crater with a diameter >10 meters, which has a semicircular shape, an elevated rim, and a central pit. Images of the impact and resulting ejecta were recorded by the Deployable CAMera 3 for >8 minutes, showing the growth of an ejecta curtain (the outer edge of the ejecta) and deposition of ejecta onto the surface. The ejecta curtain was asymmetric and heterogeneous and it never fully detached from the surface. The crater formed in the gravity-dominated regime; in other words, crater growth was limited by gravity not surface strength. We discuss implications for Ryugu's surface age.
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Eritema/patología , Histiocitoma Fibroso Benigno/patología , Neoplasias Cutáneas/patología , Adulto , Eritema/etiología , Eritema/cirugía , Femenino , Histiocitoma Fibroso Benigno/complicaciones , Histiocitoma Fibroso Benigno/cirugía , Humanos , Neoplasias Cutáneas/complicaciones , Neoplasias Cutáneas/cirugíaRESUMEN
BACKGROUND: LL-37 is an antimicrobial peptide with pleiotropic effects on the immune system, angiogenesis and tissue remodelling. These are cardinal pathological events in systemic sclerosis (SSc). OBJECTIVES: To elucidate the potential role of LL-37 in SSc. METHODS: The expression of target molecules was evaluated by immunostaining and quantitative reverse-transcription real-time polymerase chain reaction in human and murine skin. The mechanisms regulating LL-37 expression in endothelial cells were examined by gene silencing and chromatin immunoprecipitation. Serum LL-37 levels were determined by enzyme-linked immunosorbent assay. RESULTS: In SSc lesional skin, LL-37 expression was increased in dermal fibroblasts, perivascular inflammatory cells, keratinocytes and, particularly, dermal small vessels. Expression positively correlated with interferon-α expression, possibly reflecting LL-37-dependent induction of interferon-α. In SSc animal models, bleomycin-treated skin exhibited the expression pattern of CRAMP, a murine homologue of LL-37, similar to that of LL-37 in SSc lesional skin. Furthermore, Fli1+/- mice showed upregulated expression of CRAMP in dermal small vessels. Fli1 binding to the CAMP (LL-37 gene) promoter and Fli1 deficiency-dependent induction of LL-37 were also confirmed in human dermal microvascular endothelial cells. In the analysis of sera, patients with SSc had serum LL-37 levels significantly higher than in healthy controls. Furthermore, serum LL-37 levels positively correlated with skin score and the activity of alveolitis and were significantly elevated in patients with digital ulcers compared with those without. CONCLUSIONS: LL-37 upregulation, induced by Fli1 deficiency at least in endothelial cells, potentially contributes to the development of skin sclerosis, interstitial lung disease and digital ulcers in SSc.
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Catelicidinas/fisiología , Esclerodermia Sistémica/etiología , Piel/patología , Enfermedades Vasculares/etiología , Adulto , Anciano , Animales , Péptidos Catiónicos Antimicrobianos/metabolismo , Catelicidinas/metabolismo , Células Endoteliales/metabolismo , Femenino , Fibrosis/sangre , Fibrosis/etiología , Humanos , Interferón-alfa/metabolismo , Ratones Endogámicos C57BL , Persona de Mediana Edad , Proteína Proto-Oncogénica c-fli-1/deficiencia , Esclerodermia Sistémica/sangre , Regulación hacia Arriba/fisiología , Enfermedades Vasculares/sangreRESUMEN
BACKGROUND: Interleukin (IL)-33 is a recently identified cytokine, which is a member of the IL-1 family and binds to a heterodimeric receptor comprising ST2 (suppression of tumorigenicity 2) and IL-1 receptor accessory protein. Serum levels of IL-33 have been reported to be upregulated in various T helper (Th)1/Th17-mediated diseases, such as rheumatoid arthritis and inflammatory bowel disease. IL-33 expression is increased in lesional skin in patients with psoriasis, but serum levels in patients with psoriasis have not yet been studied. AIM: To study serum IL-33 levels in patients with psoriasis, a Th1/Th17-mediated skin disease, before and after anti-tumour necrosis factor (TNF)-α therapy. METHODS: Serum IL-33 levels were measured in patients with psoriasis vulgaris (PV), psoriatic arthritis (PsA) or pustular psoriasis (PP), and compared with those of healthy controls. Associations between serum IL-33 levels and serum TNF-α, IL-6, vascular endothelial growth factor and C-reactive protein levels were also studied. In addition, the effect of IL-33 stimulation on IL-6, IL-8, TNF-α and VEGF secretion by human keratinocyte was analysed. RESULTS: Serum IL-33 levels in patients with PV, PsA and PP were significantly higher than those in healthy controls. Serum IL-33 levels correlated with serum TNF-α levels in patients with psoriasis, and decreased after anti-TNF-α therapy. IL-33 stimulated IL-6 and IL-8 secretion by human keratinocytes. CONCLUSIONS: These results suggest that serum IL-33 levels generally reflect increased inflammation in patients with psoriasis.
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Interleucina-33/metabolismo , Psoriasis/metabolismo , Adulto , Análisis de Varianza , Proteína C-Reactiva/metabolismo , Estudios de Casos y Controles , Citocinas/metabolismo , Femenino , Humanos , Interleucinas/metabolismo , Queratinocitos/metabolismo , Masculino , Persona de Mediana Edad , Psoriasis/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
BACKGROUND: Lipocalin-2 is an adipocytokine implicated in apoptosis, innate immunity, angiogenesis, and the development of chronic kidney disease. OBJECTIVES: To investigate the role of lipocalin-2 in systemic sclerosis (SSc). MATERIALS AND METHODS: Serum lipocalin-2 levels were determined by enzyme-linked immunosorbent assay in 50 patients with SSc and 19 healthy subjects. Lipocalin-2 expression was evaluated in the skin of patients with SSc and bleomycin (BLM)-treated mice and in Fli1-deficient endothelial cells by reverse transcriptase-real time polymerase chain reaction, immunoblotting and/or immunohistochemistry. RESULTS: Although serum lipocalin-2 levels were comparable between patients with SSc and healthy controls, the prevalence of scleroderma renal crisis was significantly higher in patients with SSc with elevated serum lipocalin-2 levels than in those with normal levels. Furthermore, serum lipocalin-2 levels inversely correlated with estimated glomerular filtration rate in patients with SSc with renal dysfunction. Among patients with SSc with normal renal function, serum lipocalin-2 levels positively correlated with skin score in patients with diffuse cutaneous SSc with disease duration of < 3 years and inversely correlated with estimated right ventricular systolic pressure in total patients with SSc. Importantly, in SSc lesional skin, lipocalin-2 expression was increased in dermal fibroblasts and endothelial cells. In BLM-treated mice, lipocalin-2 was highly expressed in dermal fibroblasts, but not in endothelial cells. On the other hand, the deficiency of transcription factor Fli1, which is implicated in SSc vasculopathy, induced lipocalin-2 expression in cultivated endothelial cells. CONCLUSIONS: Lipocalin-2 may be involved in renal dysfunction and dermal fibrosis of SSc. Dysregulated matrix metalloproteinase-9/lipocalin-2-dependent angiogenesis due to Fli1 deficiency may contribute to the development of pulmonary arterial hypertension associated with SSc.
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Proteínas de Fase Aguda/fisiología , Lipocalinas/fisiología , Enfermedades Pulmonares/etiología , Proteínas Proto-Oncogénicas/fisiología , Insuficiencia Renal Crónica/etiología , Esclerodermia Sistémica/etiología , Piel/patología , Enfermedades Vasculares/etiología , Proteínas de Fase Aguda/metabolismo , Adulto , Anciano , Animales , Apoptosis/fisiología , Estudios de Casos y Controles , Femenino , Fibrosis/etiología , Fibrosis/patología , Fibrosis/fisiopatología , Tasa de Filtración Glomerular/fisiología , Humanos , Lipocalina 2 , Lipocalinas/metabolismo , Enfermedades Pulmonares/fisiopatología , Masculino , Ratones , Persona de Mediana Edad , Proteínas Proto-Oncogénicas/metabolismo , Esclerodermia Sistémica/patología , Esclerodermia Sistémica/fisiopatología , Enfermedades Cutáneas Vasculares/etiología , Enfermedades Cutáneas Vasculares/fisiopatología , Enfermedades Vasculares/patología , Enfermedades Vasculares/fisiopatologíaRESUMEN
BACKGROUND: The prognosis of cutaneous angiosarcoma (CAS), especially for patients with tumours > 5 cm has been reported to be dismal, even after conventional surgery and radiotherapy (S + RT). OBJECTIVES: To demonstrate the efficacy of chemoradiotherapy with taxane (T + RT) and maintenance chemotherapy. METHODS: We retrospectively reviewed 16 patients with CAS treated with T + RT and 12 patients treated with S + RT. None had distant metastasis. Tumour sites included the scalp (n = 25) and limbs (n = 3). The chemotherapy regimens used in T + RT were monthly docetaxel (n = 10), biweekly docetaxel (n = 1), weekly docetaxel (n = 5) and weekly paclitaxel (n = 1). The median radiation dose was 70 Gy. Nine patients receiving T + RT continued chemotherapy as maintenance therapy (monthly docetaxel in nine patients and monthly paclitaxel in two patients) and four patients receiving S + RT received adjuvant chemotherapy (weekly docetaxel). RESULTS: The response ratio of T + RT was 94% (14 complete remission and one partial remission). The 5-year overall survival (OS) rate of patients receiving T + RT was statistically higher than those receiving conventional S + RT (56% and 8%, respectively; P < 0·01). Moreover, patients who received T + RT with maintenance chemotherapy showed a significant improvement in OS than those receiving T + RT alone (P < 0·01). There was a strong trend for relapse-free survival, but it was not significant (P = 0·07). These data indicate that maintenance chemotherapy is crucial for long-term survival after T + RT. CONCLUSIONS: From these results, we suggest that T + RT followed by maintenance chemotherapy is a plausible method for managing CAS, especially large tumours that are difficult to manage with S + RT alone.
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Quimioradioterapia/métodos , Neoplasias de Cabeza y Cuello/terapia , Hemangiosarcoma/terapia , Cuero Cabelludo , Neoplasias Cutáneas/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Hidrocarburos Aromáticos con Puentes/administración & dosificación , Terapia Combinada , Docetaxel , Esquema de Medicación , Femenino , Neoplasias de Cabeza y Cuello/radioterapia , Neoplasias de Cabeza y Cuello/cirugía , Hemangiosarcoma/radioterapia , Hemangiosarcoma/cirugía , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/radioterapia , Recurrencia Local de Neoplasia/cirugía , Recurrencia Local de Neoplasia/terapia , Paclitaxel/administración & dosificación , Estudios Retrospectivos , Neoplasias Cutáneas/radioterapia , Neoplasias Cutáneas/cirugía , Taxoides/administración & dosificación , Resultado del TratamientoRESUMEN
Ciclosporin (Cs)A is an effective treatment for psoriasis. However, to date, the effect of CsA on the production of interleukins (ILs) is unknown. We investigated how CsA affects production of IL-12/23p40 and IL-23 production by the human monocyte cell line, THP-1, which is able to differentiate into macrophage-like cells or normal human keratinocytes (NHKs). THP-1 cells were preincubated with CsA, then stimulated with lipopolysaccharide (LPS), polyinosinic:polycytidylic acid or adenosine triphosphate. The levels of IL-12/23p40 and IL-23 released into the supernatant were assayed by ELISA. CsA significantly reduced both IL-12/23p40 and IL-23 production by LPS-stimulated THP-1 cells, but not in LPS-stimulated macrophage-like differentiated THP-1 cells. None of the stimuli used significantly induced either IL-12/23p40 or IL-23 production in NHKs. CsA inhibits not only IL-12/23p40 and IL-12p70, but also heterodimeric IL-23 production by human monocytes, which may be one possible mechanism for the therapeutic efficacy of CsA in psoriasis.
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Ciclosporina/farmacología , Inhibidores Enzimáticos/farmacología , Interleucina-12/metabolismo , Interleucina-23/metabolismo , Monocitos/efectos de los fármacos , Línea Celular , Ensayo de Inmunoadsorción Enzimática , Humanos , Monocitos/metabolismo , Psoriasis/tratamiento farmacológicoRESUMEN
BACKGROUND: CC chemokine ligand (CCL) 18 is expressed by monocytes and dendritic cells (DCs), and has potent chemotactic activity for T cells, B cells and DCs. CCL18 expression is up-regulated in lesional skin of atopic dermatitis and bullous pemphigoid, suggesting its important roles in the development of these skin diseases. OBJECTIVE: To investigate roles of CCL18 in cutaneous T-cell lymphoma (CTCL). METHODS: The CCL18 messenger RNA (mRNA) expression in CTCL skin (n = 21) and in normal skin (n = 7) was examined by quantitative RT-PCR. CCL18 expression was also examined by immunohistochemistry. Serum CCL18 levels were measured in 38 patients with CTCL and 20 healthy controls by enzyme-linked immunosorbent assay. We also analysed correlation between serum CCL18 levels and other clinical and laboratory data. RESULTS: The CTCL lesional skin contained higher levels of CCL18 mRNA than normal skin. CCL18 was expressed by dermal macrophages and DCs in CTCL skin. Serum CCL18 levels in patients with CTCL were significantly higher than those of healthy controls and correlated with types of skin lesions. They also significantly correlated with modified severity-weighted assessment scores, serum sIL-2R, LDH, IL-4, IL-10, IL-31, CCL17 and CCL26 levels. Patients with high serum levels of CCL18 showed significantly poor prognosis compared with those with low CCL18 levels. CONCLUSION: CCL18 mRNA is up-regulated in CTCL lesional skin, and serum CCL18 levels are significantly increased and correlated with the severity of CTCL. These results suggest that CCL18 may be associated with the development of CTCL.
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Quimiocinas CC/genética , Regulación Neoplásica de la Expresión Génica , Linfoma Cutáneo de Células T/genética , Neoplasias Cutáneas/genética , Adulto , Anciano , Biopsia con Aguja , Estudios de Casos y Controles , Quimiocinas CC/metabolismo , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunohistoquímica , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/fisiopatología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica/patología , Pronóstico , ARN Mensajero/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Valores de Referencia , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/fisiopatología , Estadísticas no Paramétricas , Regulación hacia ArribaRESUMEN
BACKGROUND: CD26 is a multifunctional type II transmembrane glycoprotein, which also exists as a secreted isoform, soluble CD26 (sCD26). The CD26 expression on circulating T cells is decreased in some skin diseases such as cutaneous T-cell lymphoma (CTCL) and psoriasis. It remains to be determined whether sCD26 can be used as a marker of skin diseases or not. OBJECTIVE: To investigate utility of sCD26 as a diagnostic marker of skin diseases in combination with thymus and activation-regulated chemokine (TARC). METHODS: Serum sCD26 levels were measured using enzyme-linked immunosorbent assay in 130 participants including 32 patients with atopic dermatitis (AD); 45 patients with CTCL; 26 patients with psoriasis; and 27 healthy controls. RESULTS: Serum sCD26 levels in patients with CTCL and psoriasis (162.1 ± 80.2 ng/mL and 125.4 ± 82.1 ng/mL respectively) were significantly lower than those of healthy controls (392.6 ± 198.7 ng/mL; P < 0.01 and 0.01 respectively). In patients with CTCL, serum sCD26 levels of patients with advanced stage were 135.0 ± 51.5 ng/mL and they were significantly lower than those with early stage (193.1 ± 96.0 ng/mL; P < 0.05). When we used serum sCD26 and TARC levels for diagnostic criteria, sensitivity, specificity, positive predictive value and negative predictive value for AD, CTCL and psoriasis were 65.2-73.7%, 81.4-97.6%, 65.2-94.4%, and 81.4-88.9% respectively. CONCLUSION: Serum sCD26 levels, combined with serum TARC levels, are helpful in diagnosis of AD, CTCL and psoriasis.
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Quimiocina CCL17/sangre , Dermatitis Atópica/sangre , Dipeptidil Peptidasa 4/sangre , Linfoma Cutáneo de Células T/sangre , Psoriasis/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Quimiocina CCL17/metabolismo , Dermatitis Atópica/diagnóstico , Dermatitis Atópica/fisiopatología , Dipeptidil Peptidasa 4/metabolismo , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Linfoma Cutáneo de Células T/diagnóstico , Linfoma Cutáneo de Células T/fisiopatología , Masculino , Persona de Mediana Edad , Psoriasis/diagnóstico , Psoriasis/fisiopatología , Valores de Referencia , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , SolubilidadRESUMEN
BACKGROUND: Retinol binding protein-4 (RBP-4) is a member of adipocytokines, which is potentially associated with fibrosis, vasodilation, and angiogenesis in addition to insulin resistance. OBJECTIVE: To investigate the clinical significance of serum RBP4 levels in patients with systemic sclerosis (SSc), which is a systemic autoimmune disease characterized by fibrosis and vasculopathy. METHODS: Serum RBP4 levels were determined by enzyme-linked immunosorbent assay in 62 SSc patients and 19 healthy controls. RESULTS: Similar to patients with chronic kidney disease, serum RBP4 levels inversely correlated with estimated glomerular filtration rate in SSc patients with renal dysfunction. Therefore, analyses were carried out by excluding SSc patients with estimated glomerular filtration rate <60 mL/min/1.73 m(2) . Serum RBP4 levels were significantly lower in diffuse cutaneous SSc (dcSSc) than in control subjects [median (25-75 percentile); 25.8 µg/mL (19.6-47.0) vs. 43.1 µg/mL (31.7-53.4), P < 0.05], while there was no significant difference between limited cutaneous SSc (lcSSc) [28.0 µg/mL (25.4-43.3)] and control subjects. In both of dcSSc and lcSSc, patients with Raynaud's phenomenon had RBP4 levels significantly lower than those without. Furthermore, serum RBP4 levels inversely correlated with pulmonary function test results in dcSSc and with right ventricular systolic pressure in lcSSc. CONCLUSION Decreased RBP4 levels are associated with the prevalence of Raynaud's phenomenon in dcSSc and lcSSc, with the severity of interstitial lung disease in dcSSc, and with the degree of pulmonary vascular involvement in lcSSc, suggesting the possible contribution of RBP4 to the pathological events in this disorder.
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Proteínas Plasmáticas de Unión al Retinol/metabolismo , Esclerodermia Sistémica/sangre , Ciclofosfamida/uso terapéutico , Ensayo de Inmunoadsorción Enzimática , Femenino , Tasa de Filtración Glomerular , Humanos , Enfermedades Pulmonares Intersticiales/sangre , Masculino , Persona de Mediana Edad , Enfermedad de Raynaud/sangre , Esclerodermia Sistémica/tratamiento farmacológico , Esclerodermia Sistémica/fisiopatologíaRESUMEN
BACKGROUND: Apelin is a bioactive peptide exerting its pro-angiogenic and pro-fibrotic effects in a context-dependent manner through the activation of its receptor APJ, which is ubiquitously expressed on the surface of various cell types. The activation of apelin/APJ signalling appears to be involved in the pathological process of fibrotic disorders, including liver cirrhosis. OBJECTIVE: As an initial step to clarify the role of apelin/APJ signalling in the pathogenesis of systemic sclerosis (SSc), we investigated serum apelin levels and their clinical association in patients with SSc. METHODS: Serum apelin levels were determined by a specific enzyme-linked immunosorbent assay in 56 SSc patients and 18 healthy controls. RESULTS: Serum apelin levels were comparable among three groups, including diffuse cutaneous SSc, limited cutaneous SSc and control subjects (1.77 ± 1.48, 1.63 ± 1.51 and 1.61 ± 0.44 ng/mL, respectively). When we classified SSc patients into three groups according to disease duration, serum apelin levels were elevated in early SSc (<3 years) compared with mid-stage SSc (3-10 years) (1.74 ± 1.26 vs. 1.02 ± 0.52 ng/mL, P < 0.05). Importantly, in late stage SSc (>10 years), the prevalence of severe vascular involvements, including intractable skin ulcers, scleroderma renal crisis and pulmonary arterial hypertension, was significantly higher in patients with elevated serum apelin levels than in those without (100% vs. 20%, P < 0.05). CONCLUSION: Apelin may be associated with altered and activated angiogenesis prior to fibrotic responses in early SSc and with the development of proliferative vasculopathy in late stage SSc.
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Péptidos y Proteínas de Señalización Intercelular/sangre , Neovascularización Patológica/sangre , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/fisiopatología , Adulto , Anciano , Apelina , Biomarcadores/sangre , Estudios de Casos y Controles , Progresión de la Enfermedad , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Péptidos y Proteínas de Señalización Intercelular/metabolismo , Masculino , Persona de Mediana Edad , Neovascularización Patológica/fisiopatología , Pronóstico , Valores de Referencia , Medición de Riesgo , Esclerodermia Difusa/sangre , Esclerodermia Difusa/fisiopatología , Esclerodermia Limitada/sangre , Esclerodermia Limitada/fisiopatología , Sensibilidad y Especificidad , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: A disintegrin and metalloprotease (ADAM) 12 is one of the metalloproteinase-type ADAMs and possesses extracellular metalloprotease and cell-binding functions. ADAM12 is expressed in two alternative forms, such as a membrane-anchored form (ADAM12-L) and a short secreted form (ADAM12-S). OBJECTIVE: To investigate the clinical significance of serum ADAM12-S levels in systemic sclerosis (SSc). METHODS: Serum ADAM12-S levels were determined by a specific enzyme-linked immunosorbent assay in 61 SSc patients and 18 healthy controls. RESULTS: Serum ADAM12-S levels were significantly increased in diffuse cutaneous SSc (dcSSc) patients than in healthy controls (0.417 ± 0.389 vs. 0.226 ± 0.065 ng/mL; P < 0.05), while being comparable between limited cutaneous SSc (0.282 ± 0.258 ng/mL) and healthy controls. Serum ADAM12-S levels significantly elevated in dcSSc patients with disease duration of ≤ 6 years (0.537 ± 0.449 ng/mL, P < 0.05), but not in dcSSc with disease duration of >6 years (0.225 ± 0.049 ng/mL), compared to healthy controls. Furthermore, in dcSSc patients with disease duration of ≤ 6 years, serum ADAM12-S levels correlated positively with modified Rodnan total skin thickness score, ground glass score, and serum C-reactive protein values, while showed inverse correlation with fibrosis score. CONCLUSION: Elevated serum ADAM12-S levels are associated with elevated serum inflammatory marker, severity of skin fibrosis, and activity of interstitial lung disease in dcSSc, suggesting the possible contribution of ADAM12-S to the pathological events in this disorder.
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Proteínas ADAM/sangre , Enfermedades Pulmonares Intersticiales/sangre , Enfermedades Pulmonares Intersticiales/etiología , Proteínas de la Membrana/sangre , Esclerodermia Sistémica/sangre , Esclerodermia Sistémica/complicaciones , Proteína ADAM12 , Progresión de la Enfermedad , Femenino , Fibrosis/sangre , Fibrosis/etiología , Humanos , Masculino , Persona de Mediana Edad , Piel/patología , Factores de TiempoRESUMEN
Developments in measuring sound velocity of matter under ultrahigh pressure are described. We employed a time-resolved x-ray shadowgraph technique to measure the sound velocity of shock-compressed diamond and iron foils at around melt. The sound velocity significantly dropped at melting, a behavior that has been difficult to clarify by conventional measurements by subtracting particle velocity from shock velocity (u(s) - u(p)). In addition to sound velocity, other important parameters were also obtained simultaneously.
RESUMEN
BACKGROUND: The cell surface protein CD93, expressed on endothelial and myeloid cells, mediates phagocytosis, inflammation and cell adhesion. A soluble form of CD93 (sCD93) is released during inflammation. OBJECTIVES: To determine the serum sCD93 level and its association with clinical parameters in patients with systemic sclerosis (SSc). METHODS: Serum sCD93 levels were examined by enzyme-linked immunosorbent assay in 59 patients with SSc, 24 patients with systemic lupus erythematosus and 47 healthy individuals. The expression of CD93 in skin tissues was examined immunohistochemically. In a retrospective longitudinal study, sera from 11 patients with SSc were analysed. RESULTS: Serum sCD93 levels were increased in patients with SSc compared with healthy individuals (P<0·001). Patients with diffuse cutaneous SSc showed greater levels of sCD93 than those with limited cutaneous SSc (P<0·01) or systemic lupus erythematosus (P<0·01). Serum sCD93 levels correlated positively with the severity of skin sclerosis. Strong CD93 immunostaining was observed on endothelial cells in lesional skin tissues. In the longitudinal study, sCD93 levels decreased in parallel with improvement in skin sclerosis. CONCLUSIONS: Serum sCD93 levels are increased in patients with SSc and correlate with the severity and activity of skin sclerosis. CD93 may contribute to the development of skin fibrosis in SSc.
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Glicoproteínas de Membrana/metabolismo , Receptores de Complemento/metabolismo , Esclerodermia Sistémica/sangre , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Inmunohistoquímica , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Piel/metabolismo , Adulto JovenRESUMEN
BACKGROUND: A noncanonical pathway of transforming growth factor-ß signalling, the c-Abl/protein kinase C-δ (PKC-δ)/Friend leukemia virus integration 1 (Fli1) axis, is a powerful regulator of collagen synthesis in dermal fibroblasts. OBJECTIVES: To investigate the significance of the c-Abl/PKC-δ/Fli1 pathway for the establishment of the profibrotic phenotype in lesional dermal fibroblasts from patients with localized scleroderma (LSc). METHODS: The activation status of the c-Abl/PKC-δ/Fli1 pathway was evaluated by immunoblotting and chromatin immunoprecipitation using cultured dermal fibroblasts from patients with LSc and closely matched healthy controls and by immunostaining on skin sections. The effects of a platelet-derived growth factor receptor inhibitor AG1296 and gene silencing of c-Abl on the expression levels of type I collagen were evaluated by immunoblotting. RESULTS: The phosphorylation levels of Fli1 at threonine 312 were increased, while the total Fli1 levels and the binding of Fli1 to the COL1A2 promoter were decreased, in cultured LSc fibroblasts compared with cultured normal fibroblasts. Furthermore, in cultured LSc fibroblasts, the expression levels of c-Abl were elevated compared with cultured normal fibroblasts and PKC-δ was preferentially localized in the nucleus. These findings were also confirmed in vivo by immunohistochemistry using skin sections. Moreover, gene silencing of c-Abl, but not AG1296, significantly suppressed the expression of type I collagen in cultured LSc fibroblasts. CONCLUSIONS: Constitutive activation of the c-Abl/PKC-δ/Fli1 pathway at least partially contributes to the establishment of the profibrotic phenotype in LSc dermal fibroblasts, which provides a novel molecular basis to explain the efficacy of imatinib against skin sclerosis in a certain subset of LSc.
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Fibroblastos/metabolismo , Proteína Quinasa C-delta/metabolismo , Proteína Proto-Oncogénica c-fli-1/metabolismo , Proteínas Proto-Oncogénicas c-abl/metabolismo , Esclerodermia Localizada/metabolismo , Adolescente , Adulto , Benzamidas , Estudios de Casos y Controles , Células Cultivadas , Niño , Preescolar , Femenino , Fibroblastos/efectos de los fármacos , Humanos , Mesilato de Imatinib , Masculino , Persona de Mediana Edad , Fosforilación , Piperazinas/farmacología , Proteína Quinasa C-delta/genética , Inhibidores de Proteínas Quinasas/farmacología , Proteína Proto-Oncogénica c-fli-1/genética , Pirimidinas/farmacología , Esclerodermia Localizada/genética , Factor de Crecimiento Transformador beta/efectos de los fármacos , Factor de Crecimiento Transformador beta/genética , Factor de Crecimiento Transformador beta/metabolismoRESUMEN
BACKGROUND: B-cell-activating factor belonging to the tumour necrosis factor family (BAFF) is known for its role in the survival and maturation of B cells. It has been recently suggested that BAFF also plays important roles in T-cell activation in T-cell mediated diseases such as psoriasis. OBJECTIVES: To investigate the role of BAFF in cutaneous T-cell lymphoma (CTCL). METHODS: BAFF messenger RNA (mRNA) expression in skin samples (24 CTCL cases and seven healthy controls) and in skin-derived fibroblasts (five CTCL cases and five healthy controls) was examined by quantitative reverse transcription-polymerase chain reaction. We also performed immunohistochemical staining for BAFF and its receptors. Serum BAFF levels were measured in patients with CTCL (n=46), atopic dermatitis (n=36) or psoriasis (n=27) and 27 healthy controls by enzyme-linked immunosorbent assay. RESULTS: Lesional skin of CTCL contained higher levels of BAFF mRNA than normal skin and the expression levels correlated with disease activity. BAFF mRNA expression levels were elevated in fibroblasts from CTCL skin. Tumour cells in the lesional skin of CTCL expressed BAFF and its receptors, while fibroblasts expressed only BAFF. Serum BAFF levels of CTCL patients were significantly higher than those of healthy controls and correlated with types of skin lesions and clinical stages. They also significantly correlated with serum soluble interleukin-2 receptor and lactate dehydrogenase levels. CONCLUSIONS: BAFF expression in CTCL skin and serum BAFF levels are significantly increased and correlate with the severity of CTCL. These results suggest that BAFF may have important roles in the development of CTCL.
Asunto(s)
Factor Activador de Células B/metabolismo , Linfoma Cutáneo de Células T/metabolismo , Neoplasias Cutáneas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Leucocitos Mononucleares/metabolismo , Masculino , Persona de Mediana Edad , ARN Mensajero/metabolismoRESUMEN
The protein lipocalin (LCN)-2 is known to be related to insulin resistance, obesity and atherosclerotic diseases. Psoriasis is an inflammatory skin disease related to metabolic syndrome. The aim of this study was to examine the relationship between serum LCN2 levels and indicators for metabolic syndrome and inflammatory cytokine levels in patients with psoriasis. Serum LCN2 levels were measured in patients with psoriasis, atopic dermatitis (AD) or bullous pemphigoid (BP), and compared with those of healthy controls. Serum LCN2 levels were also compared with several indicators for metabolic syndrome, and with serum levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-α, two markers of inflammation. Serum LCN2 levels in patients with psoriasis were significantly higher than those of healthy controls, but there was no significant correlation between serum LCN2 and body mass index. Serum LCN2 levels also correlated with serum IL-6 and TNF-α levels in patients with psoriasis. Serum LCN2 levels are a general indicator for increased inflammation in the patients with psoriasis.
Asunto(s)
Lipocalinas/sangre , Proteínas Proto-Oncogénicas/sangre , Psoriasis/sangre , Proteínas de Fase Aguda , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Dermatitis Atópica/sangre , Femenino , Humanos , Interleucina-6/sangre , Lipocalina 2 , Masculino , Enfermedades Metabólicas/sangre , Persona de Mediana Edad , Penfigoide Ampolloso/sangre , Factor de Necrosis Tumoral alfa/sangre , Adulto JovenRESUMEN
BACKGROUNDS: Adiponectin has been demonstrated to be one of anti-inflammatory and anti-fibrotic factors, suggesting the potential of this cytokine to be involved in the developmental process of systemic sclerosis (SSc). OBJECTIVE: The aim of this study was to investigate the clinical significance of serum adiponectin levels in patients with SSc. Methods Serum adiponectin levels were determined using enzyme-linked immunosorbent assay (ELISA) in 32 patients with diffuse cutaneous SSc (dcSSc), 28 with limited cutaneous SSc (lcSSc) and 27 healthy controls. No significant difference between these groups existed in terms of gender, age and body mass index. RESULTS: Serum adiponectin levels in dcSSc patients (4.93 ± 6.48 µg/mL) were significantly lower than those in lcSSc patients (9.69 ± 7.61 µg/mL, P < 0.01) and healthy controls (9.36 ± 5.57 µg/mL, P < 0.01). dcSSc patients with disease duration of ≤5 years had significantly decreased serum adiponectin levels (2.15 ± 1.69 µg/mL) than those with disease duration of >5 years (13.29 ± 8.36 µg/mL, P < 0.01), lcSSc patients with disease duration of ≤5 years (8.07 ± 7.98 µg/mL, P < 0.05), lcSSc patients with disease duration of >5 years (10.9 ± 7.34 µg/mL, P < 0.01) and healthy controls (9.36 ± 5.57 µg/mL, P < 0.01). Longitudinal studies in five patients with early dcSSc treated with oral prednisone demonstrated that serum adiponectin levels inversely correlate with the activity of progressive skin sclerosis in dcSSc patients. CONCLUSION: Serum levels of adiponectin may serve as a useful marker to evaluate the activity of progressive skin sclerosis in dcSSc.