RESUMEN
BACKGROUND/PURPOSE: Perceived age may be a better predictor of mortality rate than chronological age. We have demonstrated that perceived age was a significant biomarker for carotid atherosclerosis in Japanese. However, it remains to be determined which skin parameter is associated with atherosclerosis. The purpose of this study is to analyze the relationship between 10 facial skin-aging parameters and atherosclerosis in 169 middle-aged to elderly Japanese women who participated. METHODS: Facial photographs were taken under a shadowless lamp from three directions using a high-resolution digital camera. The digital images of each subject were analyzed using computer software and various parameters of skin aging such as pigmentation, wrinkles, and skin color were quantified. Carotid intima-media thickness (IMT) and brachial-ankle pulse wave velocity (baPWV) were measured as indices for atherosclerosis. RESULTS: Facial pigmentation showed a significant correlation with carotid IMT, even after correction for age (r = 0.13, P = 0.03), and with visceral fat area. Stepwise regression analysis indicated that facial pigmentation was associated with carotid IMT via visceral fat area. CONCLUSION: Facial pigmentation may be a useful biomarker for carotid atherosclerosis in Japanese women.
Asunto(s)
Enfermedades de las Arterias Carótidas/diagnóstico , Enfermedades de las Arterias Carótidas/epidemiología , Cara/patología , Pigmentación de la Piel , Piel/patología , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores , Colorimetría/métodos , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Japón/epidemiología , Persona de Mediana Edad , Fotograbar/métodos , Prevalencia , Valores de Referencia , Reproducibilidad de los Resultados , Sensibilidad y EspecificidadAsunto(s)
Anticuerpos Monoclonales Humanizados/efectos adversos , Inhibidores de Puntos de Control Inmunológico/efectos adversos , Ipilimumab/efectos adversos , Melanoma/tratamiento farmacológico , Síndrome Uveomeningoencefálico/inducido químicamente , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antineoplásicos Inmunológicos/efectos adversos , Humanos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Ipilimumab/uso terapéutico , Masculino , Persona de Mediana Edad , Triamcinolona Acetonida/administración & dosificación , Síndrome Uveomeningoencefálico/tratamiento farmacológico , Vitíligo/inducido químicamenteAsunto(s)
Artritis/patología , Granuloma/patología , Proteína Adaptadora de Señalización NOD2/genética , Sinovitis/patología , Uveítis/patología , Artritis/genética , Preescolar , Diagnóstico Diferencial , Granuloma/genética , Humanos , Masculino , Mutación , Sarcoidosis , Sinovitis/genética , Uveítis/genéticaRESUMEN
BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are characterized by keratinocyte apoptosis and necrosis, resulting in epidermal detachment. Although monocytes abundantly infiltrate the epidermis in SJS/TEN skin lesions, the properties and functions of these cells have not been fully examined. OBJECTIVES: To determine the properties of monocytes infiltrating into the epidermis in SJS/TEN. METHODS: Immunostaining of skin sections was performed to examine the membrane markers of monocytes infiltrating into skin lesions. RESULTS: Immunostaining of cryosections from 11 SJS/TEN skin lesions revealed numerous CD14+ monocytes located along the dermoepidermal junction and throughout the epidermis. The cells coexpressed CD16, CD11c and HLA-DR. CD14+ CD16+ cells were identified in very early lesions without epidermal damage, suggesting that their infiltration is a cause, rather than a result, of epidermal damage. Moreover, these cells expressed CD80, CD86 and CD137 ligand, indicative of their ability to facilitate the proliferation and cytotoxicity of CD8+ T cells. CD16+ cells infiltrating the epidermis and detected at the dermoepidermal junction were immunostained and counted in paraffin-embedded skin sections obtained from 47 patients with drug rash manifested as TEN, SJS, maculopapular-type rash or erythema multiform-type rash. The number of CD16+ monocytes infiltrating the epidermis increased significantly, depending on the grade of epidermal damage. CONCLUSIONS: These findings suggest that the appearance of CD14+ CD16+ cells of monocyte lineage plays an important role in the epidermal damage associated with SJS/TEN, most probably by enhancing the cytotoxicity of CD8+ T cells.
Asunto(s)
Receptores de Lipopolisacáridos/metabolismo , Monocitos/metabolismo , Receptores de IgG/metabolismo , Síndrome de Stevens-Johnson/patología , Ligando 4-1BB/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Apoptosis/fisiología , Antígeno B7-1/metabolismo , Antígeno B7-2/metabolismo , Linaje de la Célula , Proliferación Celular , Epidermis/patología , Femenino , Humanos , Inmunohistoquímica , Queratinocitos/patología , Masculino , Persona de Mediana Edad , Síndrome de Stevens-Johnson/inmunologíaRESUMEN
The amount of adsorbed Fe(iii) on BiVO4 particles, which is controlled by the pH and temperature of the reaction solution, strongly affects the photocatalytic performance of BiVO4 for Fe(iii) reduction. Quantum and solar-energy-conversion efficiencies of 38% and 0.65%, respectively, were achieved.
RESUMEN
Photoelectrochemical dimethoxylation of furan with methanol using a BiVO4/WO3 photoanode and Br+/Br- as a mediator was demonstrated with low applied potential. The faradaic efficiency for the dimethoxylation with a Et4NBF4 co-supporting electrolyte at +0.1 V vs. SHE was almost quantitative up to 99%.
RESUMEN
CD95 apoptosis resistance of tumor cells is often acquired through mutations in the death domain (DD) of one of the CD95 alleles. Furthermore, Type I cancer cells are resistant to induction of apoptosis by soluble CD95 ligand (CD95L), which does not induce efficient formation of the death-inducing signaling complex (DISC). Here, we report that tumor cells expressing a CD95 allele that lacks a functional DD, splenocytes from heterozygous lpr(cg) mice, which express one mutated CD95 allele, and Type I tumor cells stimulated with soluble CD95L can all die through CD95 when protein synthesis or nuclear factor kappa B is inhibited. This noncanonical form of CD95-mediated apoptosis is dependent on the enzymatic activity of procaspase-8 but does not involve fully processed active caspase-8 subunits. Our data suggest that it is possible to overcome the CD95 apoptosis resistance of many tumor cells that do not efficiently form a DISC through noncanonical activation of the caspase-8 proenzyme.
Asunto(s)
Apoptosis/fisiología , Caspasas/metabolismo , Receptor fas/fisiología , Alelos , Clorometilcetonas de Aminoácidos/farmacología , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Caspasa 8 , Inhibidores de Caspasas , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Cicloheximida/farmacología , Inhibidores de Cisteína Proteinasa/farmacología , Dactinomicina/farmacología , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte , Resistencia a Antineoplásicos , Activación Enzimática , Proteína Ligando Fas , Humanos , Glicoproteínas de Membrana/farmacología , Ratones , Ratones Endogámicos C3H , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Mutación , FN-kappa B/antagonistas & inhibidores , Oligopéptidos/farmacología , Receptores del Factor de Necrosis Tumoral/metabolismo , Receptor fas/genéticaRESUMEN
Fas antigen, which belongs to a nerve growth factor/tumor necrosis factor receptor superfamily, is a membrane protein that induces apoptosis. In humans, distribution of Fas antigen has been reported on cell lines and lymphocytes. Immunohistochemical studies revealed Fas antigen on the keratinocytes of lesional epidermis in lichenoid drug eruption, erythema multiforme, contact dermatitis, bullous pemphigoid, pemphigus vulgaris, and herpes zoster; it is co-expressed with intercellular adhesion molecule-1. Cultured keratinocytes expressing Fas antigen increased from 8.4% to 34.6% after stimulation with interferon gamma for 24 h. Treatment of interferon-gamma-stimulated keratinocytes with anti-Fas for 48 h resulted in DNA fragmentation and death of 32% of cells, suggesting that Fas antigen may mediate apoptosis. The expression of Fas antigen on keratinocytes in lesional skin suggests that death via Fas antigen may play an important role in the pathogenesis of keratinocyte cytotoxicity.
Asunto(s)
Antígenos de Superficie/análisis , Apoptosis , Queratinocitos/inmunología , Anticuerpos/farmacología , Antígenos de Superficie/inmunología , Moléculas de Adhesión Celular/metabolismo , Células Cultivadas , Daño del ADN , Citometría de Flujo , Humanos , Inmunohistoquímica , Molécula 1 de Adhesión Intercelular , Interferón gamma/farmacología , Enfermedades de la Piel/inmunología , Enfermedades de la Piel/patología , Receptor fasRESUMEN
Decay-accelerating factor (DAF) is a 70-kD membrane glycoprotein that regulates autologous complement activation, by preventing assembly of alternative or classical C3/C5 convertases, and has been shown to have a wide tissue distribution. In this study, DAF antigen has been demonstrated at the intercellular spaces of normal human epidermis with monoclonal antibody against DAF using the peroxidase-anti-peroxidase method. The amount of DAF was greater at the granular layer than the basal cell layer as judged by intensity of the staining. Western blot analysis of DAF in the epidermis showed a 55-kD band, whereas that of buffy coat cells was approximately 67 kD. When DAF of the epidermis was treated with neuraminidase, the molecular weight was reduced to 53 kD, whereas that of buffy coat cells was 56 kD. These results indicated that the content of sialic acid of DAF in the epidermis was different from that of buffy coat cells. In phosphatidylinositol-specific phospholipase C (PIPLC)-treated normal human skin, DAF was not demonstrated in the epidermis, whereas DAF remained unchanged on the elastic fibers. After the treatment of the epidermis by PIPLC, DAF was released into the buffer shown by Western blot analysis. These results suggested that DAF on the epidermis was anchored to keratinocyte via phosphatidylinositol (PI), whereas the anchoring mechanism of DAF on the elastic fibers was not through PI.
Asunto(s)
Glicoproteínas de Membrana/análisis , Proteínas de la Membrana/análisis , Piel/citología , Western Blotting , Antígenos CD55 , Células Epidérmicas , Humanos , Proteínas de la Membrana/aislamiento & purificación , Peso Molecular , Neuraminidasa , Valores de Referencia , Piel/química , Fosfolipasas de Tipo CRESUMEN
Membrane co-factor protein (MCP; CD46) is an integral membrane protein with molecular weight (MW) of the two species of 63 kD and 55 kD, and regulates autologous complement activation, with the activity of factor I cofactor. The quantity of each species is genetically regulated, and two codominantly inherited allelic variants account for the three phenotypic patterns. By immunohistochemical study, MCP was found both in the intercellular spaces of the epidermis and on the endothelial cells in the dermis of normal human skin in vivo. The intensity of the staining pattern was higher in the basal layer than in the granular layer. By Western blot analysis with use of a monoclonal antibody, MCP in the epidermis appeared as several bands ranged from 60-50 kD, with a major band of 56 kD, which was different from those in either polymorphonuclear cells, platelets, and cultured keratinocytes. No other variants were found in the epidermis obtained from skin of 20 normal humans. Complement activation in human skin may be regulated at several steps, including DAF and HRF20, thereby protecting cells from autologous complement attack.
Asunto(s)
Antígenos CD , Proteínas del Sistema Complemento/fisiología , Glicoproteínas de Membrana/análisis , Piel/química , Western Blotting , Humanos , Proteína Cofactora de Membrana , Peso MolecularRESUMEN
Mouse mammary tumor viruses (MMTV) replicate in the mammary gland, appear as infectious particles in mother's milk and invade the sucking pups from the intestinal tract. The immune system is essential for MMTV in the gut to reach the mammary gland. These properties make the life cycle of MMTV unique. We review the oncologically and immunologically intriguing events caused by MMTV in relation to the life cycle of the virus.
Asunto(s)
Virus del Tumor Mamario del Ratón/fisiología , Secuencia de Aminoácidos , Animales , Ratones , Datos de Secuencia MolecularRESUMEN
Of five autonomous sublines established independently from the transplantable hormone-dependent mouse mammary tumor, TPDMT-4, three but not two acquired metastatic potential. In in vitro culture using collagen gels, actinonin, an antibiotic protease inhibitor exerted a stronger growth-inhibiting effect on the metastatic than on the parent and non-metastatic tumors. Zymographic analysis demonstrated the active forms of gelatinases in the metastatic but not in the non-metastatic sublines and the complete inhibition of the enzyme activities by actinonin. Gelatinases/type IV collagenases might play an important role in tumor progression towards metastatic phenotype and actinonin may suppress tumor growth through inhibiting collagenase.
Asunto(s)
Gelatinasas/metabolismo , Neoplasias Mamarias Animales/enzimología , Neoplasias Mamarias Animales/patología , Animales , Recuento de Células , División Celular/efectos de los fármacos , Ácidos Hidroxámicos/farmacología , RatonesRESUMEN
In order to elucidate a possible role of metallothionein (MT) in mammary carcinogenesis, MT and sex hormone receptor (estrogen receptor, ER; progesterone receptor, PR) expressions were investigated immunohistochemically in a transplantable pregnancy-dependent mouse mammary tumor (TPDMT-4) and related autonomous tumor sublines (T4-OI96, T4-OI165 and T4-OI320CY) recovered from pregnant and virgin DDD mice. TPDMT-4 showed MT expression in tumor cells, while the expression was less evident in T4-OI165 and T4-OI96 among the autonomous tumor lines; in T4-OI320CY, the MT expression was similar to that in TPDMT-4. Chromatographic study of MT contents in the tumor lines confirmed the results of the immunohistochemical examination. PR and ER were localized in the tumor cells of TPDMT-4, but not in those of autonomous tumor sublines. In TPDMT-4, a significant correlation was observed between MT and ER expressions (r = 0.83, P < 0.01), but not between MT and PR expressions (r = 0.26, P > 0.4), also between MT expression and mitotic activity (r = -0.34, P > 0.3). Since T4-OI96 and T4-OI165 are known to be more malignant than T4-OI320CY, the present study indicates a negative correlation between the MT positivity and progression of the transplantable mammary tumor in mice.
Asunto(s)
Neoplasias Mamarias Experimentales/química , Metalotioneína/análisis , Animales , Femenino , Inmunohistoquímica , Ratones , Mitosis , Trasplante de Neoplasias , Embarazo , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Células Tumorales CultivadasRESUMEN
The recruitment of immature dendritic cells into the epidermis is a key step in the development of cutaneous immunity, although the mechanism remains to be clarified. Recently, it was reported that both macrophage inflammatory protein 3alpha (MIP-3alpha)/CCL20 produced by keratinocytes and TNF-alpha are important in recruiting Langerhans cells (LC) to the epidermis. In this study, we examined the production of MIP-3alpha by human keratinocytes stimulated with TNF-alpha. Cultured keratinocytes showed enhanced expression of MIP-3alpha mRNA and protein when stimulated with TNF-alpha. In addition, conditioned medium from TNF-alpha-stimulated keratinocyte cultures induced the migration of L1.2 cells expressing CCR6. We next examined the production of MIP-3alpha in stratified keratinocytes and found that, in contrast to non-stratified keratinocytes, stimulation with TNF-alpha increased the expression of MIP-3alpha mRNA and protein. Moreover, skin samples grown in organ culture and treated with TNF-alpha showed MIP-3alpha in the keratinocytes of the spinous layer, but not in the basal layer, by immunofluorescence staining. Based on these results, we postulate that MIP-3alpha produced by keratinocytes in the spinous layer in response to TNF-alpha stimulation is a key chemokine responsible for the epidermal recruitment of Langerhans cells.
Asunto(s)
Quimiocinas CC/genética , Regulación de la Expresión Génica/efectos de los fármacos , Queratinocitos/fisiología , Proteínas Inflamatorias de Macrófagos/genética , Receptores de Quimiocina , Fenómenos Fisiológicos de la Piel , Piel/citología , Transcripción Genética/efectos de los fármacos , Factor de Necrosis Tumoral alfa/farmacología , Diferenciación Celular , Células Cultivadas , Quimiocina CCL20 , Quimiotaxis/efectos de los fármacos , Quimiotaxis/fisiología , Humanos , Queratinocitos/citología , Queratinocitos/efectos de los fármacos , Técnicas de Cultivo de Órganos , ARN Mensajero/genética , Receptores CCR6 , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Piel/efectos de los fármacosRESUMEN
Topical vitamin D3 therapy is one of the mainstays of psoriasis treatment. However, the effectiveness of combination therapy with topical vitamin D3 and corticosteroids is still controversial. It has been reported that topical vitamin D3 treatment following topical corticosteroids is less effective than that without preceding corticosteroid treatment. We hypothesized that vitamin D receptor (VDR) in the skin is down-regulated by topical corticosteroids. To obtain support for this hypothesis, we determined VDR protein levels in cultured keratinocytes and fibroblasts after corticosteroid treatment. VDR levels were quantified by Western blot analysis with a Fluorolmager. Keratinocytes and fibroblasts were obtained from four psoriasis patients and four normal controls. VDR levels were altered in neither normal nor psoriatic keratinocytes by 2-day incubation with dexamethasone (1x10(-9)-1x10(-6) M) or clobetasol propionate (1x10(-9)-1x10(-6) M). Similarly, VDR levels in normal and psoriatic fibroblasts were not affected by 2-day incubation with dexamethasone (1x10(-6) M). These findings suggest that down-regulation of VDR by topical corticosteroids in keratinocytes and fibroblasts of psoriasis is unlikely.
Asunto(s)
Antiinflamatorios/farmacología , Clobetasol/análogos & derivados , Dexametasona/farmacología , Fibroblastos/efectos de los fármacos , Queratinocitos/efectos de los fármacos , Receptores de Calcitriol/biosíntesis , Administración Tópica , Adulto , Anciano , Western Blotting , Células Cultivadas , Clobetasol/farmacología , Regulación hacia Abajo/efectos de los fármacos , Femenino , Fibroblastos/metabolismo , Glucocorticoides , Humanos , Queratinocitos/metabolismo , Masculino , Persona de Mediana Edad , Psoriasis/metabolismo , Psoriasis/patología , Piel/citología , Piel/efectos de los fármacos , Piel/metabolismoRESUMEN
Estimating blood content in the lung remains a key step in calculating lung water volume and microvascular permeability. We studied the effect of regional lung hematocrit (Hct) variation on assessment of acute lung injury. Escherichia coli endotoxin was administered in guinea pigs intravenously. Lung injury was evaluated by measuring the wet-to-dry weight ratio (W/D) and transvascular 125I-labeled albumin leakage for 3 h [tissue-to-plasma 125I-albumin ratio (T/P)] in five tissue samples from each animal. Residual blood content was corrected using either 51Cr-red blood cells as a blood cell marker, 99mTc-albumin as a plasma marker, or both, injected 10 min before the guinea pigs were killed. Lung Hct, estimated from the marker counts of lung and peripheral blood samples, was lower than peripheral blood Hct; intraindividual variation, represented by the standard deviation in each subject, was 0.024 +/- 0.015 for the control group (coefficient of variation 8.0 +/- 5.1%) and 0.026 +/- 0.013 for the endotoxin group (coefficient of variation 8.5 +/- 4.1%). Uncorrected W/D for residual blood content was greater than the corrected W/D. 99mTc-albumin correction gave values closer to the W/D corrected by both markers. T/P corrected by 99mTc-albumin showed smaller data variations than the values obtained with 51Cr-red blood cell correction, which was affected by variations in lung Hct. We recommend using a plasma marker to correct for blood content in assessing acute lung injury by W/D and T/P.
Asunto(s)
Enfermedades Pulmonares/fisiopatología , Circulación Pulmonar/fisiología , Animales , Agua Corporal/fisiología , Radioisótopos de Cromo , Eritrocitos/fisiología , Escherichia coli , Femenino , Cobayas , Hematócrito , Lipopolisacáridos , Enfermedades Pulmonares/inducido químicamente , Tamaño de los Órganos , Volumen Plasmático/fisiología , Albúmina Sérica RadioyodadaRESUMEN
Hyperoxic lung injury is attributable to oxygen radicals produced under hyperoxic conditions. The 21-aminosteroid (AS), U-74389G, is a potent antioxidant. We examined the effect of U-74389G on lung injury in guinea pigs during exposure to 90% O2 for 48 h. We injected either vehicle or 10 mg/kg of U-74389G 30 min before the O2 exposure and injected the same dose 12, 24, and 36 h later. We performed two series of experiments after exposure. In the first series, we measured the clearance rate of 99mTc-labeled dialdehyde starch (DAS) from the lungs as an index of pulmonary epithelial damage in three experimental groups consisting of 1) control (n = 6) O2 alone (n = 6), and 3) O2 + AS (n = 6). In the second series, pulmonary endothelial injury was estimated by using 28 guinea pigs divided into four experimental groups consisting of 1) control (n = 8), 2) AS alone (n = 5), 3) O2 alone (n = 6), and 4) O2 + AS (n = 9). In the second series, we measured the wet-to-dry weight ratio (W/D) as an index of lung water and the concentration ratio of 125I-labeled albumin in lung tissue and bronchoalveolar lavage (BAL) fluid compared with plasma (T/P and BAL/P, respectively) as indexes of pulmonary endothelial damage. Cell accumulation in BAL fluid and lung tissue samples was also assessed in the second series.(ABSTRACT TRUNCATED AT 250 WORDS)
Asunto(s)
Antioxidantes/uso terapéutico , Enfermedades Pulmonares/tratamiento farmacológico , Oxígeno/toxicidad , Pregnatrienos/uso terapéutico , Animales , Recuento de Células Sanguíneas , Líquido del Lavado Bronquioalveolar/citología , Endotelio/patología , Epitelio/patología , Agua Pulmonar Extravascular/fisiología , Femenino , Cobayas , Pulmón/metabolismo , Enfermedades Pulmonares/patología , Tamaño de los Órganos/fisiología , Albúmina Sérica Radioyodada , Almidón/análogos & derivados , Compuestos de TecnecioRESUMEN
The stoichiometric splitting of water into H2 and O2 (H2/O2 = 2) under visible light irradiation (lambda > 420 nm) took place for the first time using a mixture of Pt-WO3 and Pt-SrTiO3 (Cr-Ta-doped) photocatalysts and an IO3-/I- shuttle redox mediator.