RESUMEN
BACKGROUND: Glutathione redox status, changes in intracellular reduced (GSH) or oxidized (GSSG) glutathione, plays a significant role in various aspects of cellular function. In this study, we examined whether intracellular glutathione redox status in human dendritic cells (DCs) regulates the polarization of Th1/Th2 balance. METHODS: Human monocyte-derived DCs (MD-DCs) treated with glutathione reduced form ethyl ester (GSH-OEt) or L-buthionine-(S,R)-sulfoximine (BSO) were stimulated by lipopolysaccharide (LPS), and the levels of polarization cytokines were measured. Next, DCs matured by LPS or thymic stromal lymphopoietin (TSLP) were cocultured with allogeneic CD4(+) naive T cells and Th1/Th2 balance was evaluated by cytokine production from the primed T cells. RESULTS: Monocyte-derived DCs exposed to GSH-OEt and BSO had increased and decreased intracellular GSH contents, respectively. Lipopolysaccharide-induced interleukin (IL)-27 production was enhanced by GSH-OEt and suppressed by BSO, but neither GSH-OEt nor BSO affected the expression of HLA-DR, CD80, CD83, or CD86. Mature GSH-OEt-treated MD-DCs enhanced interferon (IFN)-γ production from CD4(+) T cells compared with nontreated MD-DCs, and small interfering RNA (siRNA) against IL-27 suppressed the effect of GSH-OEt on IFN-γ production. Additionally, although human myeloid DCs activated by TSLP (TSLP-DCs) prime naïve CD4(+) T cells to differentiate into Th2 cells, treatment of TSLP-DCs with GSH-OEt reduced IL-13 production and enhanced IFN-γ production by CD4(+) T cells. Interleukin-27 siRNA attenuated the inhibitory effect of GSH-OEt on Th2 polarization. CONCLUSION: Our results reveal that Th1 and Th2 responses are controlled by intracellular glutathione redox status in DCs through IL-27 production.
Asunto(s)
Células Dendríticas/inmunología , Glutatión/metabolismo , Interleucina-17/biosíntesis , Linfocitos T/inmunología , Diferenciación Celular/inmunología , Citocinas/biosíntesis , Células Dendríticas/efectos de los fármacos , Glutatión/análogos & derivados , Glutatión/farmacología , Humanos , Espacio Intracelular/metabolismo , Lipopolisacáridos/inmunología , Oxidación-Reducción , Linfocitos T/citología , Células TH1/inmunología , Células Th2/inmunologíaRESUMEN
The Sun is the origin of all activities of the Earth, including its solid, liquid and gas states, as well as life on the Earth surface. Life was created on this planet and was further evolved after long physical/chemical processes, so that life here matches with what this planet requires. This paper contends that the Earth is located within the solar atmosphere, but we do not feel it in a daily life because of the blocking effects of the Earth's magnetic field and atmosphere, preventing the entry of the solar atmosphere directly into the Earth's domain. This paper emphasizes that we should not attempt to change the quality of the natural environment that delicate interactions between the Sun and the Earth have established for us by taking a long time.
Asunto(s)
Actividad Solar , Sistema Solar , Planeta Tierra , Ambiente , Efecto InvernaderoRESUMEN
Without the Sun, there would be no life on the Earth. Life was created on this planet in such a way that it "matches" with the natural environment and was further evolved through the physical/chemical processes, which reflect the state of the planet. This paper demonstrates that because of the existence of two barriers the Earth possesses, i.e. the atmosphere and the magnetic field, we are peacefully sitting on this planet and are not aware everyday of a number of potentially dangerous episodes that are taking place only 100 km above the Earth's surface. The aurora in the polar sky is one of the visible manifestations of the variability of the solar-terrestrial environment. It is imperative to realize, however, that what we cannot see by human eyes does not mean that they do not exist in reality. For example, during the solar declining phase in terms of visible indicators, such as sunspots on the Sun, geomagnetic activity resulting from invisible activity in the solar corona reaches a peak.
Asunto(s)
Planeta Tierra , Actividad Solar , Percepción Visual/fisiología , Adaptación Fisiológica/fisiología , Atmósfera , Campos Electromagnéticos , HumanosRESUMEN
Our sun is an average middle-aged star. Without the sun, there would be no atmosphere, no water, and no life on the Earth. The sun is constantly changing, providing the Earth with energy through a complicated chain of processes that occur in space surrounding the Earth. This paper demonstrates that life on Earth is protected by two barriers, i.e., the atmosphere and the magnetic field, against otherwise menacing events in space. Because of these shielding effects, we, peacefully sitting on the Earth's surface, are not aware of a number of critical and potentially dangerous episodes that are taking place only 100 km above the Earth's surface. The aurora, which dances in the polar sky also because of the two barriers, is sending us a crucial hint about what is happening in space.
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Atmósfera , Planeta Tierra , Sistema Solar , Animales , Campos Electromagnéticos , Medio Ambiente Extraterrestre , Humanos , Tiempo (Meteorología)RESUMEN
Participants' eye movements were recorded as they inspected a semi-realistic visual scene showing a boy, a cake, and various distractor objects. Whilst viewing this scene, they heard sentences such as 'the boy will move the cake' or 'the boy will eat the cake'. The cake was the only edible object portrayed in the scene. In each of two experiments, the onset of saccadic eye movements to the target object (the cake) was significantly later in the move condition than in the eat condition; saccades to the target were launched after the onset of the spoken word cake in the move condition, but before its onset in the eat condition. The results suggest that information at the verb can be used to restrict the domain within the context to which subsequent reference will be made by the (as yet unencountered) post-verbal grammatical object. The data support a hypothesis in which sentence processing is driven by the predictive relationships between verbs, their syntactic arguments, and the real-world contexts in which they occur.
Asunto(s)
Atención , Lectura , Movimientos Sacádicos , Semántica , Adulto , Formación de Concepto , Femenino , Humanos , Masculino , Reconocimiento Visual de Modelos , PsicolingüísticaRESUMEN
With the objective of estimating proliferation ability of epidermis of middle ear cholesteatoma, the difference in proliferating cell nuclear antigen (PCNA) staining between the skin of the bone region of the external ear canal (control skin) and cholesteatoma epidermis and the effects on PCNA staining of subepidermal inflammatory cell infiltration of cholesteatoma were immunohistochemically studied using an antibody against PCNA. Transforming growth factor-alpha (TGF-alpha) is known to promote epidermal proliferation based on autocrine mechanism. But it is not clear that cholesteatoma epidermis is actually in the state of hyperproliferation under the effect of this growth factor. To estimate the effect of TGF-alpha on epidermal proliferation ability, the authors compared the location of PCNA and TGF-alpha in the same specimen. Unlike the control skin, not only epidermal basal cell layer and suprabasal cell layer, but also more superior layers were found to have high levels of PCNA staining in the epidermis of cholesteatoma. However, in the same cholesteatoma epidermal tissue, the PCNA staining was varied and the difference was ascribable to subepidermal cell inflammation. It appeared that the proliferation ability was high in regions where subepidermal inflammatory cell infiltration was severe. These differences in microenvironment are inferred to greatly affect proliferation ability of cholesteatoma epidermis.
Asunto(s)
Colesteatoma del Oído Medio/patología , Epidermis/patología , Adulto , División Celular , Colorantes , Conducto Auditivo Externo/patología , Fibroblastos/patología , Humanos , Inmunohistoquímica , Hibridación in Situ , Inflamación , Antígeno Nuclear de Célula en Proliferación/análisis , Piel/patología , Hueso Temporal/patología , Factor de Crecimiento Transformador alfa/análisisRESUMEN
OBJECTIVE: To compare the pattern of proliferation and apoptotic cell death in cholesteatoma tissues with that in normal skin. PARTICIPANTS: The cholesteatoma tissue samples were excised from 10 patients during surgery. Normal skin specimens collected from the external ear canal of 6 of the 10 patients were used as controls. RESULTS: In all cholesteatoma tissue samples, apoptotic cells were not seen in the basal cell layer, but they were observed in the suprabasal, prickle, and granular cell layers. In skin specimens obtained from normal external ear canal skin, in which the suprabasal cell layer was comparatively small, similar kinetics of apoptotic cell death were observed. Immunohistochemical analysis using a monoclonal antibody to proliferation cell nuclear antigen demonstrated the presence of proliferating cells in the basal and suprabasal cell layers of the normal external ear canal skin, whereas in the cholesteatoma tissue samples, large numbers of proliferation cell nuclear antigen-positive cells were also observed in the prickle and granular cell layers. CONCLUSIONS: Proliferation in cholesteatoma epidermal cells is not uncontrolled, as it is in malignant tumors. Our results demonstrate an increase in the rate of proliferation and apoptotic cell death in cholesteatoma epidermis.
Asunto(s)
Colesteatoma del Oído Medio/patología , Adulto , Apoptosis , División Celular , ADN/análisis , Conducto Auditivo Externo , Femenino , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Antígeno Nuclear de Célula en Proliferación/análisis , Piel/patologíaRESUMEN
OBJECTIVE: To understand the interaction between cholesteatoma epithelium and subepithelial connective tissue as a paracrine regulation by keratinocyte growth factor. DESIGN: Preparation of a specific DNA probe from human fetal fibroblast and detection of localization of keratinocyte growth factor messenger RNA in subepithelial granulation tissue of middle-ear cholesteatoma by a nonradioactive in situ hybridization method. PARTICIPANTS: The cholesteatoma specimens were excised from 12 patients during surgery. Normal skin specimens collected from the external ear canal of six patients were used as controls. RESULTS: Signals specific for keratinocyte growth factor messenger RNA were not expressed in the normal skin of the external ear canal, but were observed in fibroblasts of subepithelial connective tissue of cholesteatoma specimens. Signals were observed only in specimens collected from patients whose subepithelial connective tissue was thick and proliferated and whose inflammation was strong. CONCLUSIONS: A paracrine regulation mechanism involving keratinocyte growth factor may exist for proliferation of epithelium of cholesteatoma. The subepithelial connective tissue of cholesteatoma may play an important role in the proliferation and development of the cholesteatoma, especially under inflammatory conditions.
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Colesteatoma/patología , Sondas de ADN/genética , Enfermedades del Oído/patología , Oído Medio/patología , Factores de Crecimiento de Fibroblastos , Regulación de la Expresión Génica/genética , Sustancias de Crecimiento/genética , ARN Mensajero/genética , Secuencia de Bases , Estudios de Casos y Controles , Epitelio/patología , Factor 10 de Crecimiento de Fibroblastos , Factor 7 de Crecimiento de Fibroblastos , Humanos , Hibridación in Situ , Inflamación , Datos de Secuencia Molecular , Transducción de Señal/genéticaRESUMEN
PURPOSE: The histopathological characteristics of middle ear cholesteatoma are hyperproliferation and differentiation of the epithelium and accompanying destruction of the bones. We directed our attention to interleukin 1 alpha (IL-1 alpha) and demonstrated localization of IL-1 alpha in the epidermis of cholesteatoma. In addition, a comparative study was made of the relationship of IL-1 alpha with the developmental stage of cholesteatoma, the degree of destruction of the auditory ossicles, presence/absence of otorrhea, and the state of subepithelium. MATERIALS AND METHODS: Middle ear cholesteatoma tissues collected during operations were used as the experimental material, and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, Western blot, and immunohistological techniques were used as methods. RESULTS: An anti-IL-1 alpha antibody-positive 17-kd band was observed in 2 of the 17 cases, whereas a 31-kd band was observed in 10 of the 17 cases. Neither the 17-kd band nor the 31-kd band was detected in normal skin tissues. The immunohistological staining showed the presence of IL-1 alpha in a region near the basal membrane of cholesteatoma epithelium. CONCLUSION: A correlation was observed between IL-1 alpha and patients with vigorous proliferation of granulation in the subepithelium. The presence of granulation in the reverse side of the eardrum plays an important role in the proliferation of cholesteatoma epithelium.
Asunto(s)
Colesteatoma del Oído Medio/metabolismo , Interleucina-1/análisis , Adulto , Anciano , Membrana Basal/metabolismo , Membrana Basal/patología , Western Blotting , Diferenciación Celular , División Celular , Niño , Preescolar , Colesteatoma del Oído Medio/patología , Osículos del Oído/metabolismo , Osículos del Oído/patología , Electroforesis en Gel de Poliacrilamida , Epidermis/metabolismo , Epidermis/patología , Epitelio/metabolismo , Epitelio/patología , Femenino , Tejido de Granulación/metabolismo , Tejido de Granulación/patología , Humanos , Técnicas para Inmunoenzimas , Masculino , Persona de Mediana Edad , Otitis Media/metabolismo , Otitis Media/patología , Dodecil Sulfato de Sodio , Hueso Temporal/metabolismo , Hueso Temporal/patologíaRESUMEN
Fifty-nine cases of tympanosclerosis were investigated clinically and pathologically, and the following results were obtained: 1) The male to female ratio was about 1:1.8 2) Calcification in the tympanic membrane was most common in the upper quadrants of the pars tensa, and never seen in the pars flaccida. 3) Calcification in the middle ear cavity was most common around the malleus. 4) Chronic otitis media was the most common complication of tympanosclerosis. 5) Preoperative audiometry revealed a stiffness curve with elevated bone conduction thresholds. 6) 54% of the patient had chronic otitis media in the contralateral ear. 7) Microscopic examination revealed calcification in the submucosa of the middle ear. 8) Postoperative hearing was improved in 49 ears (79.7%). Because there was no difference in the average postoperative hearing gain after type I and type III tympanoplasty, type III tympanoplasty is recommended to remove sclerotic masses completely.
Asunto(s)
Membrana Timpánica/patología , Adolescente , Adulto , Calcinosis , Enfermedades del Oído/complicaciones , Enfermedades del Oído/fisiopatología , Enfermedades del Oído/cirugía , Femenino , Audición , Humanos , Masculino , Persona de Mediana Edad , EsclerosisRESUMEN
Clinical studies have supported a relationship between otitis media with effusion in children and chronic otitis media in adults. Although clinical studies are numerous, relatively little is known about the histopathologic changes of the tympanic membrane in otitis media with effusion. Tympanic membranes were taken from the intermediate zone of the anteroinferior quadrant of the tympanic membrane during surgery for placement of tympanostomy tubes in 30 children (age range, 4 to 10 years) who did not show any improvement after 3 months of conservative treatment for otitis media with effusion. Control specimens were taken from normal temporal bones at autopsy. All specimens were observed with light and electron microscopy. Histologic degeneration of the tympanic membrane of patients with otitis media with effusion occurred most often in the lamina propria and the submucosal layer. There was an increase in the thickness of the tympanic membrane as a result of edema and fibrosis of the submucosal layer. A decrease in the thickness of the outer and inner fibrous layers occurred in the lamina propria. The histopathologic changes observed in the lamina propria may result in a change in the elastic properties of the tympanic membrane.
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Otitis Media con Derrame/patología , Membrana Timpánica/patología , Adulto , Capilares/patología , Niño , Preescolar , Enfermedad Crónica , Colágeno , Tejido Conectivo/patología , Edema/patología , Tejido Elástico/patología , Epitelio/patología , Feto , Fibroblastos/patología , Fibrosis , Humanos , Lactante , Microscopía Electrónica , Ventilación del Oído Medio , Membrana Mucosa/patología , Membrana Timpánica/embriologíaRESUMEN
The roles of epidermal growth factor (EGF) and epidermal growth factor receptor (EGF-R) in the proliferation and progression of the epithelium of middle ear cholesteatoma were studied. An attempt was made to elucidate the site and degree of localization of the EGF mRNA and EGF-R mRNA in the epithelium of the cholesteatoma by means of the non-radioactive in situ hybridization method. Ten cholesteatoma specimens excised during operations and six normal skin specimens (control) collected from the external ear canal were used in this study. The signal of the EGF mRNA was slightly expressed in part of the basal cells in only one of the six control specimens, while the signal was strongly expressed along the basal cells of the cholesteatoma epithelium in five of the ten specimens. The signal of the EGF-R mRNA was observed along the basal cell layer in five of the six control specimens, while the signal was strongly expressed in all layers of the cholesteatoma epithelium in all ten specimens. The expression was especially marked in the basal cell layer. These findings suggest the possibilities that abnormal expression of the EGF-R mRNA in nearly entire epithelial layers of cholesteatoma is due to overexpression of EGF-R gene, and that there is a mechanism of epithelial basal cell proliferation through an autocrine regulatory system via EGF and EGF-R.
Asunto(s)
Colesteatoma del Oído Medio/metabolismo , Factor de Crecimiento Epidérmico/metabolismo , Receptores ErbB/metabolismo , ARN Mensajero/metabolismo , Secuencia de Bases , División Celular/genética , Colesteatoma del Oído Medio/genética , Colesteatoma del Oído Medio/patología , Sondas de ADN , Factor de Crecimiento Epidérmico/genética , Epitelio/metabolismo , Epitelio/patología , Receptores ErbB/genética , Expresión Génica , Humanos , Hibridación in Situ , Datos de Secuencia Molecular , ARN Mensajero/genética , Sialadenitis/genética , Sialadenitis/metabolismo , Sialadenitis/patología , Piel/metabolismo , Piel/patología , Enfermedades de la Glándula Submandibular/genética , Enfermedades de la Glándula Submandibular/metabolismo , Enfermedades de la Glándula Submandibular/patologíaRESUMEN
Intracordal injection therapy is a surgical therapeutic modality for glottic incompetence caused by unilateral laryngeal paralysis. Atelocollagen, which has recently been attracting attention as a material for use in intracordal injection therapy that supplants silicon, was initially claimed and expected, by virtue of its salient biophysical properties, not to cause impaired wave-motion of the vocal mucosa when injected into the submucosa. Unfortunately, however, our attempt to use this material for the same purpose proved disappointingly unsuccessful, with vocal sounds produced thereafter being metallic, vocal folds becoming tense and consequently transforming the site into a muscular coat of vocal muscles. During the past 3 years, we at the Department of Otolaryngology of the Jikei University School of Medicine, have performed intracordal injection therapy with atelocollagen on 20 patients diagnosed as having unilateral laryngeal paralysis under local anesthesia using a flexible fiberscope and a stroboscope under a video monitoring system. Comparisons were made of the voice before and after injection in 6 patients receiving submucosal injection and 14 given intramuscular injection of the material. In some autopsied patients, histological findings of the treated vocal cords were scrutinized and problems regarding atelocollagen injection were investigated. Judging from pathological findings of the vocal cords after atelocollagen injection and the clinical results of this therapeutic procedure, it seems most appropriate to inject this plastic material into the vocal muscles. This will prevent atelocollagen diffusion and maintain unimpaired wave-motion of the vocal mucosa, thus resulting in an acceptable voice quality.
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Anestesia Local , Colágeno/administración & dosificación , Parálisis de los Pliegues Vocales/terapia , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Inyecciones , Masculino , Persona de Mediana Edad , Pliegues VocalesRESUMEN
Langerhans cells (LCs) are known to play an important role in the immunosurveillance system. In this study, as in others, numerous LCs were detected in the epithelial layer of acquired cholesteatoma by immunohistochemical staining. This finding suggests that cell-mediated immune responses are initiated by LCs in cholesteatoma; however, documentation concerning the microenvironment of LCs-keratinocytes in cholesteatoma is limited. Therefore, we investigated the effects of LCs on keratinocytes in vitro. To study these effects it was necessary to isolate and purify LCs. Our present study revealed that good enrichment and a high degree of purity (95%) of LCs could be obtained from neonatal rat skin using the immunomagnetic beads (Dynabeads M-450) sorting technique. These isolated LCs have the biologic activity of LCs, and Langerhans cells' conditioned medium (LCCM) stimulates DNA synthesis in thymocytes. The effect of LCCM on keratinocytes was then studied. We found that (1) LCCM stimulated DNA synthesis in keratinocytes was then studied. We found that (1) LCCM stimulated DNA synthesis in keratinocytes, but not protein synthesis, and (2) LCCM stimulated the incorporation of 3H-putrescine into keratinocytes by the activation of transglutaminase. Transglutaminase is a known marker of terminal differentiation in keratinocytes. By Western blot analysis, we identified a 17-kd immunoreactive mouse interleukin-1 alpha in LCCM. Our results imply that LCs found in cholesteatoma tissue may play an important role in stimulating both hyper-proliferation and cornification of keratinocytes; two characteristic features of cholesteatoma formation. These stimulatory effects may be due to the release of interleukin-1 or other factors by LCs.
Asunto(s)
Colesteatoma/patología , Oído Medio/patología , Interleucina-1/administración & dosificación , Queratinocitos/inmunología , Células de Langerhans/microbiología , Animales , Células Cultivadas , Oído Medio/cirugía , Epitelio , Femenino , Humanos , Immunoblotting , Inmunohistoquímica , Técnicas de Inmunoadsorción , Interleucina-1/biosíntesis , Interleucina-1/inmunología , MasculinoRESUMEN
Magnetic field records at the earth's surface contain the effects of a variety of different source currents flowing in outer space. During the last decade, several computational techniques for the use of magnetometer data have been proposed to obtain the global pattern of the electric fields and currents and Joule heating in the ionosphere. The numerical algorithm has now been enormously improved, such that simultaneous more direct or in situ measurements by satellites and radars can be incorporated into the scheme. In particular, owing to recent progress in satellite-viewed auroral images, it is possible to estimate "instantaneous" patterns of the ionospheric electrodynamic quantities over the entire polar region with a time resolution of several minutes. This report demonstrates that, contrary to our conventional views, large ionospheric currents can flow in regions of low auroral activity.