People with lung cancer usually present at a late stage in the course of their disease when their chances of long-term survival are low. At present there is little to offer for early diagnosis, even ...in those at high risk of developing the disease. Autoantibodies have been shown to be present in the circulation of people with various forms of solid tumour before cancer-associated antigens can be detected, and these molecules can be measured up to 5 years before symptomatic disease.
To assess the potential of a panel of tumour-associated autoantibody profiles as an aid to other lung cancer screening modalities.
Plasma from normal controls (n = 50), patients with non-small cell lung cancer (n = 82) and patients with small cell lung cancer (n = 22) were investigated for the presence of autoantibodies to p53, c-myc, HER2, NY-ESO-1, CAGE, MUC1 and GBU4-5 by enzyme-linked immunosorbent assay.
Raised levels of autoantibodies were seen to at least 1/7 antigens in 76% of all the patients with lung cancer plasma tested, and 89% of node-negative patients, with a specificity of 92%. There was no significant difference between the detection rates in the lung cancer subgroups, although more patients with squamous cell carcinomas (92%) could be identified.
Measurement of an autoantibody response to one or more tumour-associated antigens in an optimised panel assay may provide a sensitive and specific blood test to aid the early detection of lung cancer.
Peatlands have been subject to artificial drainage for centuries. This drainage has been in response to agricultural demand, forestry, horticultural and energy properties of peat and alleviation of ...flood risk. However, there are several environmental problems associated with drainage of peatlands. This paper describes the nature of these problems and examines the evidence for changes in hydrological and hydrochemical processes associated with these changes. Traditional black-box water balance approaches demonstrate little about wetland dynamics and therefore the science of catchment response to peat drainage is poorly understood. It is crucial that a more process-based approach be adopted within peatland ecosystems. The environmental problems associated with peat drainage have led, in part, to a recent reversal in attitudes to peatlands and we have seen a move towards wetland restoration. However, a detailed understanding of hydrological, hydrochemical and ecological process-inter-actions will be fundamental if we are to adequately restore degraded peatlands, preserve those that are still intact and understand the impacts of such management actions at the catchment scale.
Context: Severe systemic infection leads to hypercortisolism. Reduced cortisol binding proteins may accentuate the free cortisol elevations seen in systemic infection. Recently, low total cortisol ...increments after tetracosactrin have been associated with increased mortality and hemodynamic responsiveness to exogenous hydrocortisone in septic shock (SS), a phenomenon termed by some investigators as relative adrenal insufficiency (RAI).
Hypothesis: Free plasma cortisol may correspond more closely to illness severity than total cortisol, comparing SS and sepsis (S).
Design: This was a prospective study.
Setting: This study took place in a tertiary teaching hospital.
Patients: Patients had SS (n = 45) or S (n = 19) or were healthy controls (HCs; n = 10).
Aim: The aim of the study was to compare total with free cortisol, measured directly and estimated by Coolens’ method, corticosteroid-binding globulin (CBG), and albumin in patients with SS (with and without RAI) and S during acute illness, recovery, and convalescence.
Results: Comparing SS, S, and HC subjects, free cortisol levels reflected illness severity more closely than total cortisol (basal free cortisol, SS, 186 vs. S, 29 vs. HC, 13 nmol/liter, P < 0.001 compared with basal total cortisol, SS, 880 vs. S, 417 vs. HC, 352 nmol/liter, P < 0.001). Stimulated free cortisol increments varied greatly with illness category (SS, 192 vs. S, 115 vs. HC, 59 nmol/liter, P = 0.004), whereas total cortisol increments did not (SS, 474 vs. S, 576 vs. HC, 524 nmol/liter, P = 0.013). The lack of increase in total cortisol with illness severity is due to lower CBG and albumin. One third of patients with SS (15 of 45) but no S patients met a recently described criterion for RAI (total cortisol increment after tetracosactrin ≤ 248 nmol/liter). RAI patients had higher basal total cortisol (1157 vs. 756 nmol/liter; P = 0.028) and basal free cortisol (287 vs. 140 nmol/liter; P = 0.017) than non-RAI patients. Mean cortisol increments in RAI were lower (total, 99 vs. 648 nmol/liter, P < 0.001; free, 59 vs. 252 nmol/liter, P < 0.001). These differences were not due to altered CBG or albumin levels. Free cortisol levels normalized more promptly than total cortisol in convalescence. Calculated free cortisol by Coolens’ method compared closely with measured free cortisol.
Conclusions: Free cortisol is likely to be a better guide to cortisolemia in systemic infection because it corresponds more closely to illness severity. The attenuated cortisol increment after tetracosactrin in RAI is not due to low cortisol-binding proteins. Free cortisol levels can be determined reliably using total cortisol and CBG levels.
Transplantation of any biological material from a donor to a host will carry some inherent risk of disease transmission. Our aims were to summarize the totality of the published evidence about donor ...cancer transmission among kidney transplant recipients and to determine the cancer‐specific survival of these patients. We systematically reviewed all case reports, case series and registry studies that described the outcomes of kidney transplant recipients with donor cancer transmission published to December 2012. A total of 69 studies with 104 donor‐transmitted cancer cases were identified. The most common transmitted cancer types were renal cancer (n = 20, 19%), followed by melanoma (n = 18, 17%), lymphoma (n = 15, 14%) and lung cancer (n = 9, 9%). Patients with melanoma and lung cancers had the worst prognosis, with less than 50% of recipients surviving after 24 months from transplantation. Recipients with transmitted renal cancers had the best outcomes, with over 70% of recipients surviving for at least 24 months after transplantation. Overall, the risk of donor transmission of cancer appears low, but there is a high likelihood of reporting bias. Our findings support the current recommendations for rejecting organs from donors with a history of melanoma and lung cancer, but suggest that the use of donor kidneys with a history of small, incidental renal cell cancer may be reasonable.
The authors conduct an systematic review of published cases of donor‐transmitted cancer and report survival outcomes of recipients by cancer type.
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There is abundant evidence that the risk of atherosclerotic vascular disease is directly related to plasma cholesterol levels. Accordingly, all of the national and transnational screening and ...therapeutic guidelines are based on total or LDL cholesterol. This presumes that cholesterol is the most important lipoprotein‐related proatherogenic risk variable. On the contrary, risk appears to be more directly related to the number of circulating atherogenic particles that contact and enter the arterial wall than to the measured concentration of cholesterol in these lipoprotein fractions. Each of the atherogenic lipoprotein particles contains a single molecule of apolipoprotein (apo) B and therefore the concentration of apo B provides a direct measure of the number of circulating atherogenic lipoproteins. Evidence from fundamental, epidemiological and clinical trial studies indicates that apo B is superior to any of the cholesterol indices to recognize those at increased risk of vascular disease and to judge the adequacy of lipid‐lowering therapy. On the basis of this evidence, we believe that apo B should be included in all guidelines as an indicator of cardiovascular risk. In addition, the present target adopted by the Canadian guideline groups of an apo B <90 mg dL−1 in high‐risk patients should be reassessed in the light of the new clinical trial results and a new ultra‐low target of <80 mg dL−1 be considered. The evidence also indicates that the apo B/apo A‐I ratio is superior to any of the conventional cholesterol ratios in patients without symptomatic vascular disease or diabetes to evaluate the lipoprotein‐related risk of vascular disease.
Amyotrophic lateral sclerosis (ALS) is a late-onset neurological disorder characterized by death of motoneurons. Mutations in Cu/Zn superoxide dismutase-1 (SOD1) cause familial ALS but the mechanisms ...whereby they induce disease are not fully understood. Here, we use time-lapse microscopy to monitor for the first time the effect of mutant SOD1 on fast axonal transport (FAT) of bona fide cargoes in living neurons. We analyzed FAT of mitochondria that are a known target for damage by mutant SOD1 and also of membrane-bound organelles (MBOs) using EGFP-tagged amyloid precursor protein as a marker. We studied FAT in motor neurons derived from SOD1G93A transgenic mice that are a model of ALS and also in cortical neurons transfected with SOD1G93A and three further ALS-associated SOD1 mutants. We find that mutant SOD1 damages transport of both mitochondria and MBOs, and that the precise details of this damage are cargo-specific. Thus, mutant SOD1 reduces transport of MBOs in both anterograde and retrograde directions, whereas mitochondrial transport is selectively reduced in the anterograde direction. Analyses of the characteristics of mitochondrial FAT revealed that reduced anterograde movement involved defects in anterograde motor function. The selective inhibition of anterograde mitochondrial FAT enhanced their net retrograde movement to deplete mitochondria in axons. Mitochondria in mutant SOD1 expressing cells also displayed features of damage. Together, such changes to mitochondrial function and distribution are likely to compromise axonal function. These alterations represent some of the earliest pathological features so far reported in neurons of mutant SOD1 transgenic mice.
We present a quantitative morphological analysis using Hubble Space Telescope Near Infrared Camera and Multi-Object Spectrometer H160-band imaging and Advanced Camera for Surveys I775-band imaging of ...25 spectroscopically confirmed submillimetre galaxies (SMGs) which have redshifts between (). Our analysis also employs a comparison sample of more typical star-forming galaxies at similar redshifts (such as Lyman-break Galaxies) which have lower far-infrared luminosities. This is the first large-scale study of the morphologies of SMGs in the near-infrared at ∼ 0.1 arcsec resolution (≲1 kpc). We find that the half-light radii of the SMGs (rh= 2.3 ± 0.3 and 2.8 ± 0.4 kpc in the observed I and H bands, respectively) and asymmetries are not statistically distinct from the comparison sample of star-forming galaxies. However, we demonstrate that the SMG morphologies differ more between the rest-frame UV and optical bands than typical star-forming galaxies and interpret this as evidence for structured dust obscuration. We show that the composite observed H-band light profile of SMGs is better fitted with a high Sersic index (n∼ 2) than with an exponential disc suggesting the stellar structure of SMGs is best described by a spheroid/elliptical galaxy light distribution. We also compare the sizes and stellar masses of SMGs to local and high-redshift populations and find that the SMGs have stellar densities which are comparable to (or slightly larger than) local early-type galaxies and comparable to luminous, red and dense galaxies at z∼ 1.5 which have been proposed as direct SMG descendants, although the SMG stellar masses and sizes are systematically larger. Overall, our results suggest that the physical processes occurring within the galaxies are too complex to be simply characterized by the rest-frame UV/optical morphologies which appear to be essentially decoupled from all other observables, such as bolometric luminosity, stellar or dynamical mass.
This study aimed to characterize antimicrobial resistance and virulence genes in multi-drug resistant enterotoxigenic
Escherichia coli (ETEC) isolates (
n
=
117) collected from porcine post-weaning ...diarrhoea cases in Australia (1999–2005). Isolates were serotyped, antibiogram-phenotyped for 12 antimicrobial agents and genotyped by PCR for 30 plasmid-mediated antimicrobial resistance genes (ARGs), 22 intestinal and 38 extraintestinal
E. coli virulence genes (VGs). Nine serogroups were identified, the most prevalent being O149 (46.2%), O141 (11.2%) and Ont (31.6%). None of the isolates showed resistance to ceftiofur or enrofloxacin and 9.4% were resistant to florfenicol. No corresponding extended-spectrum/AmpC β-lactamase, fluoroquinolone or
floR ARGs were detected. An antimicrobial resistance index (ARI) was calculated from the combined data with a weighting for each antimicrobial agent dependent upon its significance to human health. Serogroup O141 isolates had a significantly higher ARI due to an elevated prevalence of aminoglycoside ARGs and possession of more virulence genes (VGs), including ExPEC or EHEC adhesins (
bmaE,
sfa/focDE,
fimH,
ihA) in toxin-producing strains that lacked the normally associated F4 and F18 fimbriae. Few associations between ARGs and VGs were apparent, apart from
tetC,
sfa/focDE and
ompT which, for a sub-set of O141 isolates, suggest possible plasmid acquisition from ExPEC. The multi-drug resistant ETEC ARG/VG profiles indicate a high probability of considerable strain and plasmid diversity, reflecting various selection pressures at the individual farm level rather than emergence and lateral spread of MDR resistant/virulent clones.
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