SummaryNecrotizing and crescentic glomerulonephritis (NCGN) is frequently associated with circulating antineutrophil cytoplasmic autoantibodies (ANCA). It is established that ANCA are specific for soluble enzymes of granules of polymorphonuclear neutrophil granulocytes (PMN), such as myeloperoxidase (MPO) or protease 3 (PR3). The purpose of this study was to identify membrane proteins of PMNs, and/or glomerular cells, as additional autoantigenic ANCA targets. When membrane protein fractions were prepared from PMNs and isolated human glomeruli, and immunoblotted with ANCA sera of NCGN patients, two bands with apparent molecular masses of 170 and 80-110 kD (gp170/80-110) were labeled in PMNs, and a 130-kD glycoprotein (gp130) in glomeruli. GpD0 was purified, and monoclonal and rabbit antibodies (Abs) were produced which showed the same double specificity as the patient's ANCA. Using these probes, evidence was provided that gp170/80-110 is identical with human lysosomal-assodated membrane protein 2 (h-lamp-2), because both proteins were immunologically cross-reactive and screening of a cDNA expression library from human promyelocytic leukemia cells with anti-gp130 Ab yielded a clone derived from h-lamp-2. Gp170/80-110 was localized primarily in granule membranes of resting PMNs, and was translocated to the cell surfaces by activation with FMLP. By contrast, gp130 was localized in the surface membranes of endothelial cells of human glomerular and renal interstitial capilLaries, rather than in lysosomes, as found for h-lamp-2. Potential clinical relevance of autoantibodies to gp170/80-110 and gp130 was assessed in a preliminary trial, in which ANCA sera of patients (n = 16) with NCGN were probed with purified or recombinant antigens. Specific reactivity was detected in "~90% of cases with active phases of NCGN, and frequently also in combination with autoantibodies specific for PIL3 or MPO. Collectively, these data provide evidence that h-lamp-2 in PMNs and a different, structurally related 130-kD membrane protein on the cell surface of renal microvascular endothelial cells are autoantigenic targets for ANCA in patients with active NCGN.

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To examine the association between body mass index (BMI), use of menopausal hormone therapy (HT), and incidence of uterine fibroids in postmenopausal women, 610,604 postmenopausal women without prior hysterectomy or diagnosis of fibroids were followed as part of a large United Kingdom prospective cohort study. We used Cox regression models to calculate adjusted relative risks (RRs) of surgically-confirmed fibroids (defined as a hospital admission with uterine fibroids as a primary diagnosis with a related surgical procedure), in relation to BMI and use of HT. During an average of 11.4 years of follow-up, 3561 women were admitted to hospital with surgically-confirmed fibroids. Five-year incidence rates decreased with age, from 0.50 % (1 in 200 women) at age 50–54, to 0.11 % (1 in 1000 women) at age 75–79. The 5-year rate in postmenopausal women aged 50–54 was about a quarter that seen in premenopausal women of the same age (1 in 200 vs. 1 in 50). Compared with normal weight women, obese women had a RR of surgically-detected fibroids of 1.46 (95 % CI 1.33–1.59; p < 0.0001). HT use was associated with a RR of 2.33 (95 % CI 2.18–2.49; p < 0.0001) in ever versus never users. When we analysed HT use and BMI together, obese vs. normal weight never users had a RR of 2.00 (95 % CI 1.77–2.26): the highest risks were seen in women who were obese and had ever used HT, RR = 3.30 (95 % CI 2.88–3.79). Uterine fibroids continue to occur in postmenopausal women; obesity and hormone therapy use are important modifiable risk factors.

These data show that MSCs are highly sensitive to RKIs and combination treatments incorporating IR. Expression analyses suggest that high levels of PDGF receptors may contribute to this effect.

Steam collection devices collecting aerosol particles into liquid samples are frequently used to analyze water-soluble particulate material. The fate of water-insoluble components is often neglected. In this work, we show that fresh soot particles can be suspended into pure water using a steam collection device, the particle-into-liquid sampler (PILS, Weber et al. 2001). The overall collection efficiency of freshly generated soot particles was found to be on the order of 20%. This shows that, depending on the analytic technique employed, the presence of insoluble, and/or hydrophobic particles in liquid samples from steam collection cannot be neglected. Copyright © 2018 The Author(s). Published with license by Taylor & Francis Group, LLC

Abstract. Thermal–optical measurement techniques are widely used for the monitoring of carbonaceous aerosols. Although results of different thermal–optical measurement techniques are comparable for total carbon, they can vary widely for values of elemental carbon especially in the presence of brown carbon. Charring of organic material during the inert heating phase of thermal–optical measurements has been found to be a major confounder, but no literature about investigations of structural changes during this process in atmospheric aerosols is available. In a recent study we investigated these structural changes for combustion aerosol standard (CAST) soot. Now we apply this approach to selected atmospheric aerosol filter samples and a subset of eight washed filter samples with low loadings of water-soluble organic carbon (WSOC). To investigate structural changes, Raman spectra were obtained for samples heated to the corresponding temperature levels and gas atmospheres of the EUSAAR2 and NIOSH870 protocols. The temperature levels where changes in the Raman spectra occurred (i.e., changes in structure) varied for different samples. For the washed samples with low WSOC loadings and absence of other water-soluble aerosol components such as inorganic salts, changes in structural ordering and darkening of the samples were not observed. We were able to show for the first time that the darkening of a sample (measured in terms of transmission laser signal) is not necessarily caused by an increase of structural ordering in the sample. Possible transformations at lower temperatures could include a formation of non-graphitic light-absorbing intermediate organic carbon, a release of C−H groups or a decrease of carbonyl groups.

&lt;p&gt;Elemental Carbon (EC), Black Carbon (BC) and Organic Carbon (OC) contribute a large amount to atmospheric aerosols. Due to their significant influence on climate and health, a reliable measurement of these components is essential. Nevertheless, their correct determination is not trivial and results of different measurement techniques show differences by factors up to nine especially in the presence of Brown Carbon (BrC) (e.g. Reisinger et al., 2008; Hitzenberger et al., 2006; Wonaschuetz et al., 2009). EC and OC are usually measured with thermal-optical techniques: The sample is heated stepwise, first in an inert (He) atmosphere, then in an oxidizing (He+O&lt;sub&gt;2&lt;/sub&gt;) atmosphere. The darkening of the sample during the heating procedure is traced with a laser transmission/reflection signal. Based on the progress of this signal, the amount of pyrolyzed carbon is calculated and attributed to OC in the subsequent evaluation. Despite this optical correction, the pyrolyzation of OC can lead to uncertainties in the OC/EC split (Cheng et al., 2012). Especially Brown Carbon (BrC) and water soluble organic carbons (WSOC) have a high tendency to pyrolyze and therefore bias the OC/EC split. Moreover several metal salts in the atmospheric aerosol can influence the measurement process and enhance or suppress pyrolysis of OC (Wang et al., 2010). These highly complex chemical and physical reactions are not fully investigated yet but are essential for a profound understanding of the biases in thermal-optical measurement techniques.&amp;#160;&lt;/p&gt;&lt;p&gt;The aim of the present study was to investigate the structural reorganizations of the carbonaceous materials in atmospheric aerosol samples occurring during a thermal-optical heating procedure (EUSAAR2, Cavalli et al., 2010) and to set them in relation with several properties of the samples such as ionic composition, EC, OC, BC and BrC, as well as the air mass origins during sampling of the atmospheric aerosol samples. &lt;br&gt;The changes of the internal structure of the material during the heating procedure of an EC/OC analyzer (Sunset instruments) were analyzed with Raman spectroscopy, which is sensitive to C-C bonding types and to the degree of structural ordering within the sample (Ferrari and Robertson, 2000). Different types of restructuration behavior were defined depending on the temperature levels of the EUSAAR2 protocol where measurable structural changes occur. For all samples ion chromatography was performed with a Dionex Aquion system (Thermo Fisher), BrC and BC were analyzed with the Integrating Sphere method (Wonasch&amp;#252;tz et al., 2009) and air mass back trajectories for the respective sampling days were calculated with HYSPLIT.&lt;/p&gt;