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1.
Nature ; 548(7667): 310-312, 2017 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-28816248

RESUMO

Red supergiant stars represent a late stage of the evolution of stars more massive than about nine solar masses, in which they develop complex, multi-component atmospheres. Bright spots have been detected in the atmosphere of red supergiants using interferometric imaging. Above the photosphere of a red supergiant, the molecular outer atmosphere extends up to about two stellar radii. Furthermore, the hot chromosphere (5,000 to 8,000 kelvin) and cool gas (less than 3,500 kelvin) of a red supergiant coexist at about three stellar radii. The dynamics of such complex atmospheres has been probed by ultraviolet and optical spectroscopy. The most direct approach, however, is to measure the velocity of gas at each position over the image of stars as in observations of the Sun. Here we report the mapping of the velocity field over the surface and atmosphere of the nearby red supergiant Antares. The two-dimensional velocity field map obtained from our near-infrared spectro-interferometric imaging reveals vigorous upwelling and downdrafting motions of several huge gas clumps at velocities ranging from about -20 to +20 kilometres per second in the atmosphere, which extends out to about 1.7 stellar radii. Convection alone cannot explain the observed turbulent motions and atmospheric extension, suggesting that an unidentified process is operating in the extended atmosphere.

2.
Radiologe ; 59(6): 517-522, 2019 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-31065738

RESUMO

Medical research in the field of oncologic imaging diagnostics using magnetic resonance imaging increasingly includes diffusion-weighted imaging (DWI) sequences. The DWI sequences allow insights into different microstructural diffusion properties of water molecules in tissues depending on the sequence modification used and enable visual and quantitative analysis of the acquired imaging data. In DWI, the application of intravenous gadolinium-containing contrast agents is unnecessary and only the mobility of naturally occurring water molecules in tissues is quantified. These characteristics predispose DWI as a potential candidate for emerging as an independent diagnostic tool in selected cases and specific points in question. Current clinical diagnostic studies and the ongoing technical developments, including the increasing influence of artificial intelligence in radiology, support the growing importance of DWI. Especially with respect to selective approaches for early detection of malignancies, DWI could make an essential contribution as an eligible diagnostic tool; however, prior to discussing a broader clinical implementation, challenges regarding reliable data quality, standardization and quality assurance must be overcome.


Assuntos
Imagem de Difusão por Ressonância Magnética , Neoplasias , Meios de Contraste , Humanos , Imageamento por Ressonância Magnética , Neoplasias/diagnóstico por imagem , Reprodutibilidade dos Testes
3.
Radiologe ; 58(Suppl 1): 14-19, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30003283

RESUMO

Magnetic resonance imaging (MRI) of the breast represents one of the most sensitive imaging modalities in breast cancer detection. Diffusion-weighted imaging (DWI) is a sequence variation introduced as a complementary MRI technique that relies on mapping the diffusion process of water molecules thereby providing additional information about the underlying tissue. Since water diffusion is more restricted in most malignant tumors than in benign ones owing to the higher cellularity of the rapidly proliferating neoplasia, DWI has the potential to contribute to the identification and characterization of suspicious breast lesions. Thus, DWI might increase the diagnostic accuracy of breast MRI and its clinical value. Future applications including optimized DWI sequences, technical developments in MR devices, and the application of radiomics/artificial intelligence algorithms may expand the potential of DWI in breast imaging beyond its current supplementary role.


Assuntos
Neoplasias da Mama , Imagem de Difusão por Ressonância Magnética/instrumentação , Aumento da Imagem , Mama , Feminino , Humanos , Aumento da Imagem/instrumentação , Sensibilidade e Especificidade
4.
Allergy ; 72(11): 1694-1703, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28378334

RESUMO

BACKGROUND: The antimicrobial peptide (AMP) RNase 7 is constitutively expressed in the epidermis of healthy human skin and has been found to be upregulated in chronic inflammatory skin diseases such as atopic dermatitis and psoriasis. Activated T cells in lesional skin of patients with atopic dermatitis (AD) and psoriasis (PSO) might be directly exposed to RNase 7. In addition to their antimicrobial activity, immunoregulatory functions have been published for several AMPs. In this study, we investigated immunoregulatory effects of the antimicrobial peptide RNase 7 on activated T cells. METHODS: Isolated human CD3+T cells were stimulated with RNase 7 and screened for possible effects by mRNA microarray analysis. The results of the mRNA microarray were confirmed in isolated CD4+T cells and in polarized TH2 cells using skin-derived native RNase 7 and a recombinant ribonuclease-inactive RNase 7 mutant. Activation of GATA3 was analysed by electrophoretic mobility shift assay. RESULTS: Treatment of activated human CD4+T cells and TH2 cells with RNase 7 selectively reduced the expression of TH2 cytokines (IL-13, IL-4 and IL-5). Experiments with a ribonuclease-inactive recombinant RNase 7 mutant showed that RNase 7 ribonuclease activity is dispensable for the observed regulatory effect. We further demonstrate that CD4+T cells from AD patients revealed a significantly less pronounced downregulation of IL-13 in response to RNase 7 compared to healthy control. Finally, we show that GATA3 activation was diminished upon cultivation of T cells with RNase 7. CONCLUSION: Our data indicate that RNase 7 has immunomodulatory functions on TH2 cells and decreases the production of TH2 cytokines in the skin.


Assuntos
Citocinas/efeitos dos fármacos , Ribonucleases/farmacologia , Linfócitos T/metabolismo , Células Th2/metabolismo , Células Cultivadas , Citocinas/biossíntese , Regulação para Baixo/efeitos dos fármacos , Fator de Transcrição GATA3/metabolismo , Humanos , Ativação Linfocitária , Pele/citologia , Pele/metabolismo , Dermatopatias/metabolismo , Células Th2/imunologia
5.
Radiologe ; 56(9): 810-6, 2016 Sep.
Artigo em Alemão | MEDLINE | ID: mdl-27502004

RESUMO

Despite the fact that working with asbestos and placing it on the market have been banned in Germany since 1993 according to the Ordinance on Hazardous Substances, asbestos-related diseases of the lungs and pleura are still the leading cause of death in occupational diseases. The maximum industrial usage of asbestos was reached in former West Germany in the late 1970s and in former East Germany the late 1980s. Occupational diseases, mainly mesotheliomas and lung cancer emerging now are thus caused by asbestos exposure which occurred 30-40 years earlier. It is known that the combination of smoking and asbestos exposure results in a superadditive increase in the risk to develop lung cancer. No suitable screening methods for early detection of malignant mesothelioma are currently available and the therapeutic options are still very limited; however, the national lung screening trial (NLST) has shown for the first time that by employing low-dose computed tomography (LDCT) in heavy smokers, lung cancer mortality can be significantly reduced. According to current knowledge the resulting survival benefits far outweigh the potential risks involved in the diagnostic work-up of suspicious lesions. These results in association with the recommendations of international medical societies and organizations were pivotal as the German statutory accident insurance (DGUV) decided to provide LDCT as a special occupational medical examination for workers previously exposed to asbestos and with a particularly high risk for developing lung cancer.


Assuntos
Asbestose/diagnóstico por imagem , Asbestose/epidemiologia , Detecção Precoce de Câncer/estatística & dados numéricos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/mortalidade , Mesotelioma/diagnóstico por imagem , Mesotelioma/mortalidade , Exposição Ocupacional/estatística & dados numéricos , Detecção Precoce de Câncer/métodos , Alemanha/epidemiologia , Humanos , Mesotelioma Maligno , Prevalência , Reprodutibilidade dos Testes , Fatores de Risco , Sensibilidade e Especificidade , Taxa de Sobrevida , Tomografia Computadorizada por Raios X/estatística & dados numéricos
6.
Pneumologie ; 70(12): 782-812, 2016 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-27931056

RESUMO

During the last 1.5 years an update of the guideline on silicosis was made by an interdisciplinary working group. New medical and scientific knowledge and the experience in expert opinion practice were taken into account.By preparing the initial guideline in 2010 standardization of diagnostics and adaption of the "Moers convention" which was not based on medical knowledge was in the focus, whereas the current update deals with fine emendation and extension, especially of the compensation rate (adaption with the Reichenhall recommendation).The diagnosis of silicosis (including mixed dust pneumoconiosis) is based on a detailed occupational history, and predominantly on the typical radiological findings. However, at initial diagnosis the standardized LD-HRCT takes an important role because of its high sensitivity and specificity. Exceptional cases are those with characteristic findings in chest X-ray follow-up. Correspondingly, it is mentioned in the guideline: "The standardized appraisal of the Low-Dose-Volume HRCT requires application of the CT classification (ICOERD, International Classification of Occupational and Environmental Respiratory diseases). In order to diagnose silicosis in CT scan opacities with sharp borders in both central upper lung fields and their circumferencies have to be documented. By comparing with ILO standard radiographs at least profusion category 1 in the right and left upper lung fields has to be reached (total profusion category 2)."The pathologic minimal requirement for the diagnosis of silicosis which has undergone controversial discussion has now also been defined. Corresponding to Hnizdo et al. 2000 it is now mentioned: "Finding of less than 5 silicotic granuloma per lung lobe by palpation is regarded as insignificant." This is a convention and not a threshold based on detailed medical scientific and statistical studies; it is based on extended experience in the South African gold mines.This guideline also deals with silicotic hilar (and sometimes mediastinial) lymph nodes; according to the guideline working group they do not closely correlate with the degree of pulmonary involvement. Extended conglomerating and enduring lymph-node processes may lead to dislocation of the hili with impairment of large bronchi and vessels. Shell-like calcifications dominating in the periphery of lymph nodes produce so-called egg-shell hili.The paragraph on exercise testing is now extended: if neither ergometry nor spiroergometry can be performed a 6 minute walking test by measuring oxygen saturation should be done.Furthermore, in individual expert opinion examinations right heart catheterization (the patient is not obliged to give informed consent) may be recommended, if echo cardiography gives evidence for pulmonary hypertension or if it is difficult to differentiate between right and left heart failure. The presence of pulmonary hypertension which is of prognostic relevance has to be considered when grading reduction in earning capacity.For interpretation of spirometry values the new GLI reference values has to be applied. Grading of impairment is due to the recommendation of the DGP.According to current medical scientific knowledge it is unclear, whether certain disorders of the rheumatic group such is scleroderma or Caplan syndrome which are sometimes associated with silicosis (or coal workers' pneumoconiosis) belong in toto to the occupational disease number 4101 (silicosis). Within this context, additional studies are needed to clarify the role of occupational quartz exposure and other risk factors.The guideline working group hopes that this update will help to optimize diagnostics and expert opinion of silicotic patients.


Assuntos
Antracose/diagnóstico , Doenças Profissionais/diagnóstico , Medicina do Trabalho/normas , Guias de Prática Clínica como Assunto , Pneumologia/normas , Silicose/diagnóstico , Diagnóstico por Imagem/normas , Medicina Baseada em Evidências , Prova Pericial/normas , Alemanha , Humanos , Testes de Função Respiratória/normas
7.
Radiologe ; 54(12): 1189-98, 2014 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-25476403

RESUMO

BACKGROUND: In the year 2012, out of the 10 most frequently recognized occupational diseases 6 were forms of pneumoconiosis. With respect to healthcare and economic aspects, silicosis and asbestos-associated diseases are of foremost importance. The latter are to be found everywhere and are not restricted to large industrial areas. PROBLEM: Radiology has a central role in the diagnosis and evaluation of occupational lung disorders. In cases of known exposure mainly to asbestos and quartz, the diagnosis of pneumoconiosis, with few exceptions will be established primarily by the radiological findings. As these disorders are asymptomatic for a long time they are quite often detected as incidental findings in examinations for other reasons. Therefore, radiologists have to be familiar with the pattern of findings of the most frequent forms of pneumoconiosis and the differential diagnoses. STANDARDIZED PROCEDURE IN EXAMINATIONS: For reasons of equal treatment of the insured a quality-based, standardized performance, documentation and evaluation of radiological examinations is required in preventive procedures and evaluations. Above all, a standardized low-dose protocol has to be used in computed tomography (CT) examinations, although individualized concerning the dose, in order to keep radiation exposure as low as possible for the patient. STANDARDIZED EVALUATION: The International Labour Office (ILO) classification for the coding of chest X-rays and the international classification of occupational and environmental respiratory diseases (ICOERD) classification used since 2004 for CT examinations meet the requirements of the insured and the occupational insurance associations as a means of reproducible and comparable data for decision-making.


Assuntos
Doenças Pulmonares Intersticiais/diagnóstico por imagem , Medicina do Trabalho/normas , Pneumoconiose/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Pneumologia/normas , Tomografia Computadorizada por Raios X/normas , Diagnóstico Diferencial , Alemanha , Humanos , Pneumoconiose/classificação , Doses de Radiação , Proteção Radiológica/normas
8.
Radiologe ; 54(4): 363-84, 2014 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-24737105

RESUMO

The high-resolution computed tomography (HRCT) coding scheme of the international classification of occupational and environmental respiratory diseases (ICOERD) presented here is an instrument for a standardized semiquantitative description of occupation and environment-linked as well as other pulmonary and pleural diseases. Analogous to the International Labour Organization (ILO) classification, the ICOERD coding scheme should always be used when the CT/HRCT examination is employed for occupational medical investigations or expert opinions. After publication of the guidelines and recommendations on diagnostics and expert assessment of asbestos-linked diseases and silicosis, the application of a standardized investigation program and assessment with the ICOERD classification form are obligatory, at least for the initial assessment. Furthermore, its use in the field of follow-up assessments of occupational diseases should be encouraged in order to guarantee comparability between individual reports (interreader variability) and at least a semiquantitative assessment of disease progression in isolated cases. Because the anatomical structures in projection radiography and CT are not presented identically, a 1:1 transfer of the results of the ILO classification to the CT/HRCT coding scheme is not possible. An overview image of the thorax does not allow overlap-free reproduction of structures, in contrast to CT. These methodological differences can in cases of isolated assessment result in different opinions of projection and CT images mostly by different investigators. In cases of discrepant opinions an integrated report of findings by combination of all information from both procedures is necessary.


Assuntos
Doença Ambiental/diagnóstico por imagem , Classificação Internacional de Doenças/normas , Doenças Profissionais/diagnóstico por imagem , Guias de Prática Clínica como Assunto , Radiologia/normas , Doenças Torácicas/diagnóstico por imagem , Tomografia Computadorizada por Raios X/normas , Alemanha , Humanos
9.
Radiologie (Heidelb) ; 2024 Jul 16.
Artigo em Alemão | MEDLINE | ID: mdl-39012478

RESUMO

A variety of workplace exposures (organic or inorganic dusts as well as gases, fumes, or vapors) can cause diffuse interstitial lung disease. The latency period until onset of the disease can exceed 30 years. The disease course varies greatly and depends on the quantity of the inhaled substance and its fibrogenic effect. Pulmonary high-resolution computed tomography (HRCT) patterns do not differ significantly from those of interstitial lung diseases (ILD) of other etiologies. Therefore, without knowledge of the occupational history, work-related ILDs are often classified as idiopathic. In addition, there is increasing evidence in the recent literature that high exposure to silica dust can trigger autoimmune diseases (also involving the lungs). For this reason, a qualified occupational history is now an indispensable part of the interdisciplinary diagnosis of ILDs.

10.
Sci Rep ; 14(1): 1122, 2024 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-38212346

RESUMO

In this work, the quasi-analog to discrete transition occurring in the current-voltage characteristic of oxygen engineered yttrium oxide-based resistive random-access memory (RRAM) devices is investigated in detail. In particular, the focus of our research is not on the absolute conductance values of this characteristic but on the magnitude of its conductance changes occurring during the reset process of the device. It is found that the detected changes correspond to conductance values predominantly of the order of the quantum unit of conductance G0 = 2e2/h, where e is the electron charge and h the Planck constant. This feature is observed even at conductance levels far above G0, i.e. where electron transport is seemingly diffusive. It is also observed that such behavior is reproducible across devices comprising yttrium oxide layers with different oxygen concentrations and measured under different voltage sweep rates. While the oxygen deficiency affects the total number of quantized conductance states, the magnitude of the changes in conductance, close to 1 G0, is invariant to the oxygen content of the functional layer.

11.
Horm Metab Res ; 45(9): 629-39, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23632905

RESUMO

Several investigations have shown a relation between diabetes and alterations of the liver circadian clock. We investigated the diurnal expression of clock genes and clock-controlled genes (CCGs) in 3-hour intervals for a 24-h period in the livers of male streptozotocin (STZ)-treated rats, male spontaneous type 1 diabetic LEW.1AR1-iddm (Iddm) rats, and Iddm rats treated for 10 days with insulin. Hepatic mRNA was extracted, and the relative expression of clock genes (Per1, Per2, Bmal1, Clock, Cry1), as well as CCGs (Dbp, E4bp4, RevErbα, Rorα, Pparγ), was analyzed by reverse transcription followed by real-time polymerase chain reaction. Diabetic STZ and Iddm rats, as well as insulin-substituted Iddm rats, exhibited a significant diurnal expression pattern of clock genes as determined by Cosinor analysis; however, the MESOR (midline estimating statistic of rhythm) of Bmal1, Per2, and Clock transcript expression was altered in Iddm and insulin-substituted Iddm rats. The hepatic expression of the CCGs Dbp and RevErbα revealed a diurnal rhythm in all investigated groups. Insulin administration to Iddm rats normalized the enhanced MESOR in the expression of Dbp, RevErbα, and E4bp4 to the levels of normoglycemic controls. Cosinor analysis indicated no diurnal rhythm of Pparγ expression in the livers of diabetic STZ or Iddm rats or in those of insulin-substituted Iddm rats. Also, insulin substitution could not reverse the decreased MESOR of Pparγ expression in Iddm rats. In consequence of the diabetic disease, changes in the expression of clock genes and CCGs suggest alterations in the hepatic peripheral clock mechanism.


Assuntos
Proteínas CLOCK/genética , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Tipo 1/genética , Regulação da Expressão Gênica , Fígado/metabolismo , Animais , Glicemia/metabolismo , Peso Corporal , Proteínas CLOCK/metabolismo , Ritmo Circadiano/genética , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/sangue , Insulina/sangue , Fígado/patologia , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real
12.
Horm Metab Res ; 44(6): 442-50, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22488520

RESUMO

The glucose transporter GLUT4 is well known to facilitate the transport of blood glucose into insulin-sensitive muscle and adipose tissue. In this study, molecular, immunohistochemical, and Western blot investigations revealed evidence that GLUT4 is also located in the mouse, rat, and human endocrine pancreas. In addition, high glucose decreased and insulin elevated the GLUT4 expression in pancreatic α-cells. In contrast, high glucose increased GLUT4 expression, whereas insulin led to a reduced expression level of the glucose transporter in pancreatic ß-cells. In vivo experiments showed that in pancreatic tissue of type 2 diabetic rats as well as type 2 diabetic patients, the GLUT4 expression is significantly increased compared to the nondiabetic control group. Furthermore, type 1 diabetic rats exhibited reduced GLUT4 transcript levels in pancreatic tissue, whereas insulin treatment of type 1 diabetic animals enhanced the GLUT4 expression back to control levels. These data provide evidence for the existence of GLUT4 in the endocrine pancreas and indicate a physiological relevance of this glucose transporter as well as characteristic changes in diabetic disease.


Assuntos
Transportador de Glucose Tipo 4/metabolismo , Ilhotas Pancreáticas/patologia , Ilhotas Pancreáticas/fisiopatologia , Adulto , Idoso , Animais , Especificidade de Anticorpos/imunologia , Linhagem Celular , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Experimental/fisiopatologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/fisiopatologia , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/fisiopatologia , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Glucose/farmacologia , Transportador de Glucose Tipo 2/genética , Transportador de Glucose Tipo 2/metabolismo , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/imunologia , Humanos , Insulina/farmacologia , Ilhotas Pancreáticas/efeitos dos fármacos , Masculino , Camundongos , Pessoa de Meia-Idade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar
13.
J Pineal Res ; 52(4): 389-96, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21929683

RESUMO

In this paper, we analyze the biological relevance of melatonin in diabetogenesis. As has recently been demonstrated, melatonin decreases insulin secretion via specific melatonin receptor isoforms (MT1 and MT2) in the pancreatic ß-cells. In addition, type 2 diabetic rats, as well as patients, exhibit decreased melatonin levels, whereas the levels in type 1 diabetic rats are increased. The latter effects were normalized by insulin substitution, which signifies that a specific receptor-mediated insulin-melatonin antagonism exists. These results are in agreement with several recent genome-wide association studies, which have identified a number of single nucleotide polymorphisms in the MTNR1B gene, encoding the MT2 receptor, that were closely associated with a higher prognostic risk of developing type 2 diabetes. We hypothesize that catecholamines, which decrease insulin levels and stimulate melatonin synthesis, control insulin-melatonin interactions. The present results support this assertion as we show that catecholamines are increased in type 1 but are diminished in type 2 diabetes. Another important line of inquiry involves the fact that melatonin protects the ß-cells against functional overcharge and, consequently, hinders the development of type 2 diabetes. In this context, it is striking that at advanced ages, melatonin levels are reduced and the incidence of type 2 diabetes is increased. Thus, melatonin appears to have a protective biological role. Here, we strongly repudiate misconceptions, resulting from observations that melatonin reduces the plasma insulin level, that the blockage of melatonin receptors would be of benefit in the treatment of type 2 diabetes.


Assuntos
Diabetes Mellitus Experimental/metabolismo , Epinefrina/metabolismo , Insulina/metabolismo , Melatonina/metabolismo , Norepinefrina/metabolismo , Animais , Glicemia/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Tipo 1/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Epinefrina/sangue , Insulina/sangue , Antagonistas da Insulina/metabolismo , Masculino , Melatonina/sangue , Norepinefrina/sangue , Glândula Pineal/metabolismo , Ratos , Ratos Wistar , Receptor de Insulina/metabolismo , Estatísticas não Paramétricas
14.
Nanotechnology ; 23(30): 305202, 2012 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-22750846

RESUMO

In the context of investigations of physical, chemical and electrical properties of ultra-thin layers of epitaxial and monocrystalline Sr(0.3)Ba(0.7)O on Si(100), we also investigated their thermal stability with x-ray photoelectron spectroscopy (XPS), electron energy loss spectroscopy (EELS), and low energy electron diffraction (LEED). At temperatures above 400 °C, transformation into silicate layers sets in. The stoichiometry after complete transformation was determined to be close to (Ba(0.8)Sr(0.2))(2)SiO(4) except for layers of only a few monolayers, where the silicate is not stoichiometric. There are strong indications that this silicate is stable until it desorbs at temperatures above 750 °C. Crystallinity, as seen with LEED, is lost during this transformation. Although transformation into silicate is coupled with metal desorption and compactification of the layers, they seem to remain closed. In addition, traces of Ba silicide at the Si interface were detected after layer desorption. This silicide cannot be desorbed thermally. The silicate layer has a bandgap of 5.9 ± 0.2 eV already for 3 ML thickness. Upon exposure to air, carbon and oxygen containing species, but no hydroxide, are formed irreversibly.

15.
Diabetologia ; 54(7): 1831-40, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-21491159

RESUMO

AIMS/HYPOTHESIS: It is well documented that melatonin influences insulin secretion mediated by G-protein-coupled melatonin receptor isoforms MT1 and MT2, which are present in rat and human pancreatic islets, as well as in rat insulinoma cells. Recent investigations have proven that hyperinsulinaemic Goto-Kakizaki (GK) rats, which are a rat model of type 2 diabetic rats, and humans have decreased melatonin plasma levels, whereas a streptozotocin-induced rat model of diabetes developed reduced insulin levels combined with increased melatonin levels. METHODS: Plasma levels of glucose, insulin and melatonin as well as RNA expression of pineal Aanat, Hiomt (also known as Asmt), insulin receptor, adrenoceptor ß1 and the clock genes Per1 and Bmal1 (also known as Arntl) were determined in male and female LEW.1AR1-iddm rats as well as in insulin-substituted LEW.1AR1-iddm rats. RESULTS: Severe hypoinsulinaemia in diabetic LEW.1AR1-iddm rats was associated with decreased body weight and increased melatonin plasma levels combined with mainly elevated expression of Aanat, Hiomt, pineal insulin receptor and adrenoceptor ß1. The changes were normalised by insulin substitution. Diurnal profiles of plasma melatonin and of antagonistic clock genes Per1 and Bmal1 were maintained in diabetic and insulin-substituted rats. CONCLUSIONS/INTERPRETATION: The assumed causal relation between elevated melatonin and reduced insulin levels in LEW.1AR1-iddm rats is supported by the observation that insulin substitution normalised these changes. Further support for this interpretation comes from the observation that in GK rats an increase of plasma insulin was combined with a decrease of plasma noradrenaline (norepinephrine), the most important activator of melatonin synthesis. These relationships between the noradrenergic and insulin pathway support the existence of melatonin-insulin antagonism.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 1/metabolismo , Insulina/sangue , Melatonina/sangue , Fatores de Transcrição ARNTL/genética , Acetilserotonina O-Metiltransferasa/genética , Animais , Arilalquilamina N-Acetiltransferase/genética , Glicemia/metabolismo , Modelos Animais de Doenças , Feminino , Masculino , Proteínas Circadianas Period/genética , Glândula Pineal/metabolismo , Ratos , Receptor de Insulina/genética , Receptores Adrenérgicos beta 1/genética , Reação em Cadeia da Polimerase Via Transcriptase Reversa
16.
Mycoses ; 54(4): e201-4, 2011 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19925568

RESUMO

We describe a 61-year-old male patient with a history of long-term corticosteroid treatment for chronic obstructive pulmonary disease, who developed subcutaneous nodules on his right forearm. Histopathologic examination showed large epitheloid cell granulomas with multinuclear giant cells that contained hyphae within their cytoplasm. Microbiological testing of biopsies revealed an infection with Scedosporium apiospermum with resistance to common antifungal agents like fluconazole, itraconazole or amphotericin B and sensitivity to voriconazole. After two months of oral therapy with voriconazole the skin lesions have completely cleared according to clinical and sonographic investigations. Adverse effects like nausea and increased photosensitivity immediately disappeared after finishing the 6-month period of voriconazole treatment.


Assuntos
Antifúngicos/administração & dosagem , Dermatomicoses/diagnóstico , Dermatomicoses/patologia , Pirimidinas/administração & dosagem , Scedosporium/isolamento & purificação , Triazóis/administração & dosagem , Corticosteroides/administração & dosagem , Corticosteroides/efeitos adversos , Braço/patologia , Biópsia , Dermatomicoses/tratamento farmacológico , Dermatomicoses/microbiologia , Farmacorresistência Fúngica , Histocitoquímica , Humanos , Hospedeiro Imunocomprometido , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Masculino , Testes de Sensibilidade Microbiana , Microscopia , Pessoa de Meia-Idade , Pele/patologia , Resultado do Tratamento , Voriconazol
17.
J Exp Med ; 170(5): 1769-74, 1989 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-2509627

RESUMO

A metabolic pathway by which L-arginine (L-arg) is converted to the biologically active compound NO. has recently been described in macrophages (M phi) and endothelial cells. This report demonstrates that transferable products from activated Kupffer cells (KC) induce the conversion of large quantities of L-arg to nitrogen oxides within hepatocytes (HC). In M phi and endothelial cells, citrulline and NO2-/NO3- are the stable endproducts of this metabolic pathway. In contrast, HC L-arg metabolism resulted in significantly greater production of NO2-/NO3- than citrulline. The generation of NO. within HC was associated with a concurrent decrease in total protein synthesis.


Assuntos
Arginina/metabolismo , Inflamação/metabolismo , Células de Kupffer/fisiologia , Fígado/metabolismo , Óxidos de Nitrogênio/metabolismo , Animais , Células Cultivadas , Ferredoxinas/metabolismo , Técnicas In Vitro , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Biossíntese de Proteínas , Ratos , Fatores de Tempo
18.
J Exp Med ; 188(6): 1185-90, 1998 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-9743536

RESUMO

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family designated APRIL (for a proliferation-inducing ligand). Although transcripts of APRIL are of low abundance in normal tissues, high levels of mRNA are detected in transformed cell lines, and in human cancers of colon, thyroid, and lymphoid tissues in vivo. The addition of recombinant APRIL to various tumor cells stimulates their proliferation. Moreover, APRIL-transfected NIH-3T3 cells show an increased rate of tumor growth in nude mice compared with the parental cell line. These findings suggest that APRIL may be implicated in the regulation of tumor cell growth.


Assuntos
Substâncias de Crescimento/fisiologia , Proteínas de Membrana/fisiologia , Células Tumorais Cultivadas/patologia , Fator de Necrose Tumoral alfa/fisiologia , Células 3T3 , Sequência de Aminoácidos , Animais , Divisão Celular/efeitos dos fármacos , Humanos , Ligantes , Linfoma de Células B , Proteínas de Membrana/biossíntese , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Dados de Sequência Molecular , Transplante de Neoplasias , RNA Mensageiro/biossíntese , Transfecção , Células Tumorais Cultivadas/efeitos dos fármacos , Células Tumorais Cultivadas/metabolismo , Membro 13 da Superfamília de Ligantes de Fatores de Necrose Tumoral
19.
J Exp Med ; 189(11): 1747-56, 1999 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-10359578

RESUMO

Members of the tumor necrosis factor (TNF) family induce pleiotropic biological responses, including cell growth, differentiation, and even death. Here we describe a novel member of the TNF family, designated BAFF (for B cell activating factor belonging to the TNF family), which is expressed by T cells and dendritic cells. Human BAFF was mapped to chromosome 13q32-34. Membrane-bound BAFF was processed and secreted through the action of a protease whose specificity matches that of the furin family of proprotein convertases. The expression of BAFF receptor appeared to be restricted to B cells. Both membrane-bound and soluble BAFF induced proliferation of anti-immunoglobulin M-stimulated peripheral blood B lymphocytes. Moreover, increased amounts of immunoglobulins were found in supernatants of germinal center-like B cells costimulated with BAFF. These results suggest that BAFF plays an important role as costimulator of B cell proliferation and function.


Assuntos
Linfócitos B/imunologia , Proteínas de Membrana/fisiologia , Receptores do Fator de Necrose Tumoral/fisiologia , Fator de Necrose Tumoral alfa/fisiologia , Sequência de Aminoácidos , Animais , Fator Ativador de Células B , Linfócitos B/citologia , Sequência de Bases , Divisão Celular , Linhagem Celular , Mapeamento Cromossômico , Cromossomos Humanos Par 13/genética , Clonagem Molecular , Primers do DNA/genética , Células Dendríticas/imunologia , Humanos , Ligantes , Ativação Linfocitária , Proteínas de Membrana/genética , Camundongos , Dados de Sequência Molecular , Receptores do Fator de Necrose Tumoral/genética , Homologia de Sequência de Aminoácidos , Linfócitos T/imunologia , Fator de Necrose Tumoral alfa/genética
20.
Science ; 250(4977): 123-5, 1990 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-2218504

RESUMO

Rhodopsin is a member of a family of receptors that contain seven transmembrane helices and are coupled to G proteins. The nature of the interactions between rhodopsin mutants and the G protein, transduction (Gt), was investigated by flash photolysis in order to monitor directly Gt binding and dissociation. Three mutant opsins with alterations in their cytoplasmic loops bound 11-cis-retinal to yield pigments with native rhodopsin absorption spectra, but they failed to stimulate the guanosine triphosphatase activity of Gt. The opsin mutations included reversal of a charged pair conserved in all G protein-coupled receptors at the cytoplasmic border of the third transmembrane helix (mutant CD1), replacement of 13 amino acids in the second cytoplasmic loop (mutant CD2), and deletion of 13 amino acids from the third cytoplasmic loop (mutant EF1). Whereas mutant CD1 failed to bind Gt, mutants CD2 and EF1 showed normal Gt binding but failed to release Gt in the presence of guanosine triphosphate. Therefore, it appears that at least the second and third cytoplasmic loops of rhodopsin are required for activation of bound Gt.


Assuntos
Mutação , Rodopsina/metabolismo , Transducina/metabolismo , Sequência de Aminoácidos , Animais , Linhagem Celular , Membrana Celular/metabolismo , Deleção Cromossômica , Micelas , Modelos Moleculares , Dados de Sequência Molecular , Fotólise , Ligação Proteica , Conformação Proteica , Rodopsina/genética , Transfecção
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