The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision
The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision
dRetinol-binding protein 4 (RBP4), the sole retinol transporter in blood, is secreted from adipocytes and liver. Serum RBP4 levels correlate highly with insulin resistance, other metabolic syndrome factors, and cardiovascular disease. Elevated serum RBP4 causes insulin resistance, but the molecular mechanisms are unknown. Here we show that RBP4 induces expression of proinflammatory cytokines in mouse and human macrophages and thereby indirectly inhibits insulin signaling in cocultured adipocytes. This occurs through activation of c-Jun N-terminal protein kinase (JNK) and Toll-like receptor 4 (TLR4) pathways independent of the RBP4 receptor, STRA6. RBP4 effects are markedly attenuated in JNK1 ؊/؊ JNK2 ؊/؊ macrophages and TLR4؊/؊ macrophages. Because RBP4 is a retinol-binding protein, we investigated whether these effects are retinol dependent. Unexpectedly, retinol-free RBP4 (apo-RBP4) is as potent as retinol-bound RBP4 (holo-RBP4) in inducing proinflammatory cytokines in macrophages. Apo-RBP4 is likely to be physiologically significant since RBP4/retinol ratios are increased in serum of lean and obese insulin-resistant humans compared to ratios in insulin-sensitive humans, indicating that higher apo-RBP4 is associated with insulin resistance independent of obesity. Thus, RBP4 may cause insulin resistance by contributing to the development of an inflammatory state in adipose tissue through activation of proinflammatory cytokines in macrophages. This process reveals a novel JNK-and TLR4-dependent and retinol-and STRA6-independent mechanism of action for RBP4.O besity is a major risk factor for insulin resistance, which is a critical pathogenic factor in type 2 diabetes (50). Determination of the physiologic and cellular mechanisms linking obesity to type 2 diabetes could lead to development of new prevention and treatment approaches. Multiple mechanisms may contribute, including abnormal production of adipocyte-secreted proteins (adipokines) (1,15,29), infiltration of white adipose tissue (WAT) with proinflammatory macrophages (42), and aberrant lipid deposition in tissues such as muscle and liver (51). These mechanisms are not mutually exclusive. For example, adipokines can affect inflammation and lipid deposition in tissues (15).Serum retinol-binding protein 4 (RBP4) is an adipokine and is also secreted by liver. RBP4 levels are increased in obese and insulin-resistant humans and mouse models, and genetic or pharmacologic elevation of serum RBP4 causes insulin resistance in normal mice (19,31,65). Although many studies show strong correlations of serum RBP4 levels with obesity and the severity of insulin resistance (9,16,27,35), others do not (8,17,32,46), as reviewed in reference 32. This may result from the use of different populations of human subjects or from methodological issues with RBP4 assays (18,32,64). Many studies also show that serum RBP4 levels correlate with other components of the metabolic syndrome in humans, including hypertension (47, 54, 64), dyslipidemia (41, 47, 64, 67), waist/hip ratio (31...
The field of interventional oncology with use of image-guided tumor ablation requires standardization of terminology and reporting criteria to facilitate effective communication of ideas and appropriate comparison between treatments that use different technologies, such as chemical (ethanol or acetic acid) ablation, and thermal therapies, such as radiofrequency (RF), laser, microwave, ultrasound, and cryoablation. This document provides a framework that will hopefully facilitate the clearest communication between investigators and will provide the greatest flexibility in comparison between the many new, exciting, and emerging technologies. An appropriate vehicle for reporting the various aspects of image-guided ablation therapy, including classification of therapies and procedure terms, appropriate descriptors of imaging guidance, and terminology to define imaging and pathologic findings, are outlined. Methods for standardizing the reporting of follow-up findings and complications and other important aspects that require attention when reporting clinical results are addressed. It is the group's intention that adherence to the recommendations will facilitate achievement of the group's main objective: improved precision
Background Retinol-binding protein 4 (RBP4) may play an important role in the etiology of insulin resistance and metabolic syndrome. Few prospective data are available on the relationship between RBP4 and coronary heart disease (CHD). Further, previous studies did not distinguish among full-length and truncated forms of RBP4 that might have various biological activities. Methods and Results We measured plasma levels of full-length and several C-terminally truncated sub-fractions of RBP4 among 468 women who developed CHD and 472 matched controls in the Nurses’ Health Study cohort during 16 years of follow-up (1990–2006). We observed a temporal variation in the association of full-length RBP4 levels with CHD risk (P=0.04 for testing proportional hazard assumption). In the first 8 years of follow-up, after multivariate adjustment for covariates, the odds ratio (OR) of CHD risk comparing extreme quartiles of full-length RBP4 levels was 3.56 (95% CI: 1.21, 10.51; Ptrend=0.003), whereas this association was 0.77 (0.38, 1.56; Ptrend=0.44) in the follow-up period of 9–16 years. Results were similar for total RBP4 levels (summed levels of all RBP4 isoforms). Levels of the primary truncated isoform, RBP4-L, were not associated with CHD risk in any follow-up period; the ORs (95% CI) for extreme quartiles were 1.29 (0.50, 3.32) and 1.20 (0.64, 2.26) in the first and second 8 years of follow-up, respectively. Conclusions In this cohort of women, higher circulating full-length and total RBP4 levels were associated with increased risk of CHD in a time-dependent fashion. Additional data are warranted to confirm the current findings.
We have investigated the photophysics of 1-aminonaphthalene and NN'-dimethyl-1aminonaphthalene in a variety of solvents. We find that the red shift of the emission spectrum, which is observed in polar solvents, is a consequence of two relaxation mechanisms. The first is an intramolecular reorganisation of the amino substituent that is stabilised by quite small changes in the solutes environment. The second, which is only observed when the solvent is moderately fluid, is a bulk relaxation of the solvent dipoles about the solutes excited-state dipole moment. A combination of these two effects results in a fluorescent state that has significant charge-transfer character. The nature of this state and the relationship between our observations and those made on more complex aminonaphthalene derivatives are discussed.
Genetic variations and posttranslational modificationsgive rise to structural diversity in fully expressed human proteins. Structural modifications can also be induced during the life cycle of a protein and can lead to impaired functioning and pathological conditions. Although a large number of protein modifications have been discovered thus far, their incidence among the general population has not been determined. Here we show that human proteins exhibit a wide range of modifications present at various frequencies in the general population. The screening of 1,000 individuals from four geographical regions in the United States for five plasma proteins revealed the existence of 27 protein modifications. Some variants, such as those resulting from oxidation and single amino acid terminal truncations, were observed in the majority of individuals, whereas point mutations and extensive sequence truncations were detected in only a few individuals. Gender correlations were observed for two protein modifications. The data obtained reveal the extent of structural diversity in the general populace and represent the first such catalogue of structural protein modifications. Systematic studies of this kind will help redefine the normal human proteome and reveal the effects of these modifications in pathological processes. Molecular & Cellular Proteomics 6:1183-1187, 2007.Protein modifications are common for many proteins and occur as a result of genetic variations and postexpression processing. Whereas modifications at the gene level can readily be studied on a large scale, the changes that occur at the protein level have been much harder to assess across larger populations. Recent advances in mass spectrometric methods of detection and sample processing have opened up the realms of population proteomics wherein human proteins are investigated across and within populations to define and understand protein difference and to facilitate the discovery and validation of disease-specific protein modulations (1, 2). Mass spectrometry measures a unique feature of each fully expressed protein, its molecular mass. Changes in the protein structure resulting from structural modifications are reflected in its molecular mass and can be detected via MS without a priori knowledge of the modification. In regard to sample processing, high throughput immunoaffinity methods can be used for protein retrieval from complex biological samples such as human plasma or serum in preparation for MS detection. The resulting mass spectrometric immunoassays (3) are ideally suited for studying structural diversity in human proteins within large populations. In a recent pilot study using MS immunoassays, 25 plasma proteins from 96 healthy individuals were examined, yielding a total of 53 structural variants with various frequencies in the sample cohort (4). Here we greatly expand the number of samples to get an accurate view of the distribution of some of these protein modifications in the general population. One thousand individuals from four geographical r...
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