tbuckley/cabot-search huggingface dataset:
Malignancy-associated metabolic profiling of human glioma cell lines using 1H NMR spectroscopy
Authors: Wei Shao, Jinping Gu, Caihua Huang, Dan Liu, Huiying Huang, Zicheng Huang, Zhen Lin, Wensheng Yang, Kun Liu, Donghai Lin, Tianhai Ji
Journal: Molecular Cancer (2014)

Ambiguity in malignant transformation of glioma has made prognostic diagnosis very challenging. Tumor malignant transformation is closely correlated with specific alterations of the metabolic profile. Exploration of the underlying metabolic alterations in glioma cells of different malignant degree is therefore vital to develop metabolic biomarkers for prognosis monitoring. We conducted 1H nuclear magnetic resonance (NMR)-based metabolic analysis on cell lines (CHG5, SHG44, U87, U118, U251) developed from gliomas of different malignant grades (WHO II and WHO IV). Several methods were applied to analyze the 1H-NMR spectral data of polar extracts of cell lines and to identify characteristic metabolites, including principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), fuzzy c-means clustering (FCM) analysis and orthogonal projection to latent structure with discriminant analysis (OPLS-DA). The expression analyses of glial fibrillary acidic protein (GFAP) and matrix metal proteinases (MMP-9) were used to assess malignant behaviors of cell lines. GeneGo pathway analysis was used to associate characteristic metabolites with malignant behavior protein markers GFAP and MMP-9. Stable and distinct metabolic profiles of the five cell lines were obtained. The metabolic profiles of the low malignancy grade group (CHG5, SHG44) were clearly distinguished from those of the high malignancy grade group (U87, U118, U251). Seventeen characteristic metabolites were identified that could distinguish the metabolic profiles of the two groups, nine of which were mapped to processes related to GFAP and MMP-9. Furthermore, the results from both quantitative comparison and metabolic correlation analysis indicated that the significantly altered metabolites were primarily involved in perturbation of metabolic pathways of tricarboxylic acid (TCA) cycle anaplerotic flux, amino acid metabolism, anti-oxidant mechanism and choline metabolism, which could be correlated with the changes in the glioma cells' malignant behaviors. Our results reveal the metabolic heterogeneity of glioma cell lines with different degrees of malignancy. The obtained metabolic profiles and characteristic metabolites are closely associated with the malignant features of glioma cells, which may lay the basis for both determining the molecular mechanisms underlying glioma malignant transformation and exploiting non-invasive biomarkers for prognosis monitoring.
Safety of long-acting β2-agonists in asthma: Table 1
Authors: Fernando Maria de Benedictis, Ines Carloni
Journal: Thorax (2012)

Safety of long-acting β2-agonists in asthmaIn their review on the safety of long-acting β2-agonists in asthma, Rodrigo et al 1 report that severe asthma-related complications were more frequent in patients receiving 1014
Cathepsin H and napsin A are active in the alveoli and increased in alveolar proteinosis
Authors: M. Woischnik, A. Bauer, R. Aboutaam, A. Pamir, F. Stanzel, J. de Blic, M. Griese
Journal: European Respiratory Journal (2008)

Pulmonary alveolar proteinosis (PAP) is a group of rare diseases with disturbed homeostasis of alveolar surfactant. While 90% of the primary adult forms are caused by granulocyte-macrophage colony-stimulating factor autoantibodies, the underlying cause of the juvenile form remains unknown. In order to distinguish primary from secondary effects in the pathogenesis of these two forms, the present authors studied the surfactant protein processing proteases napsin A and cathepsin H. In total, 16 controls, 20 patients with juvenile PAP and 13 adults with idiopathic PAP were enrolled. Amounts and activities of the proteases in the bronchoalveolar lavage fluid (BALF) were determined by immunoblotting and specific substrate cleavage. Both proteases were present and active in BALF from controls and increased in juvenile and adult PAP patients. The amount of active cathepsin H in relation to total cathepsin H was increased in PAP patients compared with controls. Cystatin C, the physiological inhibitor of cathepsin H in the alveolar space, was not increased to the same degree as cathepsin H, resulting in an imbalance of inhibitor to protease in the alveolar space. A general defect in napsin A or cathepsin H expression or activity was not the specific cause for abnormal surfactant accumulation in juvenile pulmonary alveolar proteinosis.
PTU-061 Outcomes of paediatric liver transplant recipients following transition from paediatric to adult healthcare services
Authors: N Sagar, J Leithead, D Kelly, D Adams, J Arkley, B Gunson, P McKiernan, M Smith, P Lewis, J Ferguson
Journal: Gut (2012)

<h3>Introduction</h3> Given the success of paediatric transplantation, there is now a growing population of patients that undergo transition from paediatric to adult healthcare services. In the renal transplant setting, these patients appear to be at increased risk of short-term graft loss.<sup>1</sup> However, the outcome of liver transplant patients who undergo transition remains unclear. Our aim was, therefore, to examine the patient and graft survival of liver transplant patients who undergo paediatric to adult healthcare transition. <h3>Methods</h3> Single-centre retrospective study of 85 liver transplant recipients who underwent transition from paediatric to adult healthcare services between March 2001 and August 2011 (median follow-up time from transition 4.1 (range 0.2–10.7) years). <h3>Results</h3> During the 10-year period, there were 48 (56.5%) males and 37 (43.5%) females. The median age at time of transplant was 8.4 (range 0.6–17.9) years. The initial indications for transplantation were: biliary atresia (27.1%), Wilson9s (14.1%), other acute liver failure (11.8%), cystic fibrosis (9.4%), autoimmune hepatitis (8.2%), cryptogenic cirrhosis (4.7%), oxalosis (4.7%), other (20.0%). At the time of transition, the median age of the patients was 18.9 (range 16.6–23.1) years. 84.7% of patients were on their first graft, 12.9% were on their second and 2.4% were on their third at this point. The immunosuppression at transition was calcineurin inhibitor (CNI) monotherapy in 38.2%, a CNI combination regimen in 20.6%, and a CNI free regimen in 41.2%. Following transition, the estimated 1-, 5- and 10-year patient survival was 98.6%, 96.8% and 91.4%, respectively, and the estimated 1-, 5- and 10-year graft survival was 98.6%, 95.0% and 89.4%. <h3>Conclusion</h3> Our results demonstrate that paediatric liver transplant recipients have a better outcome than previously reported in renal transplant recipients after transition.<sup>1</sup> This may suggest that this group of patients are more tolerant of their graft or that transition was adequately managed. <h3>Competing interests</h3> None declared. <h3>Reference</h3> 1. <b>Watson AR</b>. Non-compliance and transfer from paediatric to adult transplant unit. <i>Pediatr Nephrol</i> 2000;<b>14</b>:469–72.
Treatment of Varicose Ulcers
Authors: C. G. Owen
Journal: BMJ (1945)

<h3>ABSTRACT</h3> The five <i>Plasmodium</i> spp. that cause human malaria appear similar under light microscopy, which raises the possibility that misdiagnosis could routinely occur in clinical settings. Assessing the extent of misdiagnosis is of particular importance for monitoring <i>P. knowlesi</i>, which co-circulates with the other <i>Plasmodium</i> spp. We performed a systematic review and meta-analysis of studies comparing the performance of microscopy and PCR for diagnosing malaria in settings with co-circulation of the five <i>Plasmodium</i> spp. We assessed the extent to which co-circulation of <i>Plasmodium</i> parasites affects diagnostic outcomes. We fit a Bayesian hierarchical latent class model to estimate variation in microscopy sensitivity and specificity. Mean sensitivity of microscopy was low, yet highly variable across <i>Plasmodium</i> spp., ranging from 41.7% (95% CI: 22.8 – 64.1%) for <i>P. falciparum</i> and 40.3% (22.0 – 61.5%) for <i>P. vivax</i> to 0.119% (0.0121 – 0.640%) for <i>P. knowlesi</i>, 7.57% (2.66 – 22.0%) for <i>P. malariae</i>, and 0.180% (0.00491 – 1.21%) for <i>P. ovale</i>. Observed PCR prevalence was positively correlated with estimated microscopic sensitivity and negatively correlated with estimated microscopic specificity, though the strength of the associations varied by species. Our analysis suggests that co-circulation of <i>Plasmodium</i> spp. undermines the accuracy of microscopy. Sensitivity was considerably lower for <i>P. knowlesi, P. malariae</i>, and <i>P. ovale</i>. The negative association between specificity and prevalence imply that less frequently encountered species may be misdiagnosed as more frequently encountered species. Together, these results suggest that the burden of <i>P. knowlesi, P. malariae</i>, and <i>P. ovale</i> may be underappreciated in a clinical setting.
Strategy for detection of prostate cancer based on relation between prostate specific antigen at age 40-55 and long term risk of metastasis: case-control study
Authors: A. J. Vickers, D. Ulmert, D. D. Sjoberg, C. J. Bennette, T. Bjork, A. Gerdtsson, J. Manjer, P. M. Nilsson, A. Dahlin, A. Bjartell, P. T. Scardino, H. Lilja
Journal: BMJ (2013)

<b>Objective</b> To determine the association between concentration of prostate specific antigen (PSA) at age 40-55 and subsequent risk of prostate cancer metastasis and mortality in an unscreened population to evaluate when to start screening for prostate cancer and whether rescreening could be risk stratified. <b>Design</b> Case-control study with 1:3 matching nested within a highly representative population based cohort study. <b>Setting</b> Malmö Preventive Project, Sweden. <b>Participants</b> 21 277 Swedish men aged 27-52 (74% of the eligible population) who provided blood at baseline in 1974-84, and 4922 men invited to provide a second sample six years later. Rates of PSA testing remained extremely low during median follow-up of 27 years. <b>Main outcome measures</b> Metastasis or death from prostate cancer ascertained by review of case notes. <b>Results</b> Risk of death from prostate cancer was associated with baseline PSA: 44% (95% confidence interval 34% to 53%) of deaths occurred in men with a PSA concentration in the highest 10th of the distribution of concentrations at age 45-49 (≥1.6 µg/L), with a similar proportion for the highest 10th at age 51-55 (≥2.4 µg/L: 44%, 32% to 56%). Although a 25-30 year risk of prostate cancer metastasis could not be ruled out by concentrations below the median at age 45-49 (0.68 µg/L) or 51-55 (0.85 µg/L), the 15 year risk remained low at 0.09% (0.03% to 0.23%) at age 45-49 and 0.28% (0.11% to 0.66%) at age 51-55, suggesting that longer intervals between screening would be appropriate in this group. <b>Conclusion</b> Measurement of PSA concentration in early midlife can identify a small group of men at increased risk of prostate cancer metastasis several decades later. Careful surveillance is warranted in these men. Given existing data on the risk of death by PSA concentration at age 60, these results suggest that three lifetime PSA tests (mid to late 40s, early 50s, and 60) are probably sufficient for at least half of men.
Prognostic factors at diagnosis and value of WHO classification in a mono-institutional series of 180 non-functioning pancreatic endocrine tumours
Authors: R. Bettini, L. Boninsegna, W. Mantovani, P. Capelli, C. Bassi, P. Pederzoli, G.F. Delle Fave, F. Panzuto, A. Scarpa, M. Falconi
Journal: Annals of Oncology (2008)
Fas ligand is expressed in normal skin and in some cutaneous malignancies
Authors: None Lee, None Jang, None Lee, None Kim, None Park, None Shin, None Dong, None NA, None Kim, None Kim, None Kim, None Yoo
Journal: British Journal of Dermatology (1998)

Fas, a cell surface receptor and member of the tumour necrosis factor receptor superfamily, induces apoptosis upon oligomerization by its ligand (Fas ligand: FasL). Detailed studies have revealed that Fas is broadly expressed in normal human tissues, but relatively little is known about the range of cell types capable of expressing FasL. The aim of this study was to determine the in vivo patterns of expression of Fas and FasL in human skin tissues. Immunohistochemistry was performed using paraffin-embedded samples of normal and neoplastic skin tissues. In normal skin, FasL was expressed in the epidermis, sebaceous glands, sweat glands and outer root sheath of the hair. In squamous cell carcinomas (SCC), all cases analysed expressed FasL at high levels, whereas 60% of basal cell carcinomas (BCC) were positive for FasL. Expression of Fas in normal skin was observed in the basal and spinous layers of the epidermis, the outer root sheath of the hair, and the sebaceous glands. Expression of Fas was observed in all the SCC tested and none of the BCC tested. Expression of FasL by normal cells and tumour cells in skin tissue, demonstrated for the first time in the present study, may provide an important clue to understanding skin physiology, and immune evasion of skin tumours.
Obesity and the outcome of young breast cancer patients in the UK: the POSH study
Authors: E.R. Copson, R.I. Cutress, T. Maishman, B.K. Eccles, S. Gerty, L. Stanton, D.G. Altman, L. Durcan, C. Wong, P.D. Simmonds, L. Jones, D.M. Eccles
Journal: Annals of Oncology (2014)
2-Aminoadipic acid is a biomarker for diabetes risk
Authors: Thomas J. Wang, Debby Ngo, Nikolaos Psychogios, Andre Dejam, Martin G. Larson, Ramachandran S. Vasan, Anahita Ghorbani, John O’Sullivan, Susan Cheng, Eugene P. Rhee, Sumita Sinha, Elizabeth McCabe, Caroline S. Fox, Christopher J. O’Donnell, Jennifer E. Ho, Jose C. Florez, Martin Magnusson, Kerry A. Pierce, Amanda L. Souza, Yi Yu, Christian Carter, Peter E. Light, Olle Melander, Clary B. Clish, Robert E. Gerszten
Journal: Journal of Clinical Investigation (2013)

Improvements in metabolite-profiling techniques are providing increased breadth of coverage of the human metabolome and may highlight biomarkers and pathways in common diseases such as diabetes. Using a metabolomics platform that analyzes intermediary organic acids, purines, pyrimidines, and other compounds, we performed a nested case-control study of 188 individuals who developed diabetes and 188 propensity-matched controls from 2,422 normoglycemic participants followed for 12 years in the Framingham Heart Study. The metabolite 2-aminoadipic acid (2-AAA) was most strongly associated with the risk of developing diabetes. Individuals with 2-AAA concentrations in the top quartile had greater than a 4-fold risk of developing diabetes. Levels of 2-AAA were not well correlated with other metabolite biomarkers of diabetes, such as branched chain amino acids and aromatic amino acids, suggesting they report on a distinct pathophysiological pathway. In experimental studies, administration of 2-AAA lowered fasting plasma glucose levels in mice fed both standard chow and high-fat diets. Further, 2-AAA treatment enhanced insulin secretion from a pancreatic β cell line as well as murine and human islets. These data highlight a metabolite not previously associated with diabetes risk that is increased up to 12 years before the onset of overt disease. Our findings suggest that 2-AAA is a marker of diabetes risk and a potential modulator of glucose homeostasis in humans.
Long-term clinical effects of interferon gamma-1b and colchicine in idiopathic pulmonary fibrosis
Authors: K. M. Antoniou, A. G. Nicholson, M. Dimadi, K. Malagari, P. Latsi, A. Rapti, N. Tzanakis, R. Trigidou, V. Polychronopoulos, D. Bouros
Journal: European Respiratory Journal (2006)

Idiopathic pulmonary fibrosis (IPF)/usual interstitial pneumonia is a deadly disease with no effective treatment. The purpose of this randomised prospective multicentric study was to characterise the clinical effects of interferon gamma (IFN-γ) 1b administered subcutaneously thrice weekly versus colchicine for 2 yrs. This study had no pre-specified end-points. Fifty consecutive IPF patients were randomised. Patients with mild-to-moderate IPF were eligible for the study if they had histologically proven IPF, or, in the absence of surgical biopsy, fulfilled the European Respiratory Society/American Thoracic Society criteria. In the intent-to-treat population, five out of 32 (15.6%) IFN-γ-1b patients and seven out of 18 (38.8%) colchicine patients died after a median follow-up period of 25 months Patients treated with IFN-γ 1b showed a better outcome after 2 yrs of therapy, and fewer symptoms, as assessed using the St George’s Respiratory Questionnaire, after 12 months of therapy. Also, the IFN-γ-1b group exhibited a higher forced vital capacity (percentage of the predicted value) after 24 months of treatment. No significant differences were detected in resting arterial oxygen tension, total lung capacity (% pred), transfer factor of the lung for carbon monoxide (% pred) and high-resolution computed tomographic scoring between the two treatment groups. These data suggest that long-term treatment with interferon gamma 1b may improve survival and outcome in patients with mild-to-moderate idiopathic pulmonary fibrosis. Further studies are needed to verify these results.
Mortality From Lymphohematopoietic Malignancies and Brain Cancer Among Embalmers Exposed to Formaldehyde
Authors: M. Hauptmann, P. A. Stewart, J. H. Lubin, L. E. Beane Freeman, R. W. Hornung, R. F. Herrick, R. N. Hoover, J. F. Fraumeni, A. Blair, R. B. Hayes
Journal: JNCI Journal of the National Cancer Institute (2009)

Excess mortality from lymphohematopoietic malignancies, in particular myeloid leukemia, and brain cancer has been found in surveys of anatomists, pathologists, and funeral industry workers, all of whom may have worked with formaldehyde. We investigated the relation of mortality to work practices and formaldehyde exposure levels among these professionals to address cancer risk in the funeral industry. Professionals employed in the funeral industry who died between January 1, 1960, and January 1, 1986, from lymphohematopoietic malignancies (n = 168) or brain tumors (n = 48) (ie, case subjects) were compared with deceased matched control subjects (n = 265) with regard to lifetime work practices and exposures in the funeral industry, which were obtained by interviews with next of kin and coworkers, and to estimated levels of formaldehyde exposure. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated by use of logistic regression. All statistical tests were two-sided. Mortality from myeloid leukemia increased statistically significantly with increasing number of years of embalming ( P for trend = .020) and with increasing peak formaldehyde exposure ( P for trend = .036). Compared with subjects who performed fewer than 500 lifetime embalmings, mortality from myeloid leukemia was elevated among those who performed embalmings for more than 34 years (OR = 3.9, 95% CI = 1.2 to 12.5, P = .024), who performed more than 3068 embalmings (OR = 3.0, 95% CI = 1.0 to 9.2, P = .057), and those whose estimated cumulative formaldehyde exposure exceeded 9253 parts per million–hours (OR = 3.1; 95% CI = 1.0 to 9.6, P = .047). These exposures were not related to other lymphohematopoietic malignancies or to brain cancer. Duration of embalming practice and related formaldehyde exposures in the funeral industry were associated with statistically significantly increased risk for mortality from myeloid leukemia.
Cooperative and Antagonistic Interplay between PU.1 and GATA-2 in the Specification of Myeloid Cell Fates
Authors: Jonathan C. Walsh, Rodney P. DeKoter, Hyun-Jun Lee, Erica D. Smith, David W. Lancki, Michael F. Gurish, Daniel S. Friend, Richard L. Stevens, John Anastasi, Harinder Singh
Journal: Immunity (2002)
Selective uptake of high-density lipoprotein–associated cholesteryl esters by human hepatocytes in primary culture
Authors: Franz Rinninger, May Brundert, Stefan Jäckle, Peter R. Galle, Christoph Busch, Jakob R. Izbicki, Xavier Rogiers, Doris Henne-Bruns, Bernd Kremer, Christoph E. Broelsch, Heiner Greten
Journal: Hepatology (1994)

High-density lipoprotein cholesteryl esters are taken up by many cells without simultaneous uptake of high-density lipoprotein apolipoproteins. This selective uptake was investigated in human hepatocytes in primary culture. Human high-density lipoprotein-3 (density, 1.125 to 1.21 gm/ml) was radiolabeled in both its apolipoprotein and in its cholesteryl ester moiety; uptake of these high-density lipoprotein3 tracers by hepatocytes was investigated. Apparent high-density lipoprotein3 particle uptake as measured with the cholesteryl ester tracer was in excess of that from the apolipoprotein tracer, indicating selective uptake of high-density lipoprotein3 cholesteryl esters by hepatocytes. This selective uptake is a regulated pathway in hepatocytes, as demonstrated by an inverse relationship between cell cholesterol and the rate of selective uptake. Studies on the mechanism of selective uptake have used inhibitors such as monensin, chloroquine, heparin, and a monoclonal antibody directed against low-density lipoprotein receptors. These experiments provide no evidence for a role of cell-secreted apolipoprotein E, endocytosis or retroendocytosis in selective uptake. The intracellular fate of high-density lipoprotein3-associated cholesteryl esters was investigated with [3H]cholesteryl oleate-labeled high-density lipoprotein3. Hepatocytes hydrolyzed [3H]cholesteryl oleate internalized from labeled high-density lipoprotein3; this catabolism was not inhibited by the presence of chloroquine. In parallel hepatocytes were incubated with [3H]cholesteryl oleate-labeled low-density lipoprotein. Cells hydrolyzed [3H]cholesteryl oleate taken up with low-density lipoprotein; however, this hydrolysis was inhibited by chloroquine, indicating lysosomal low-density lipoprotein cholesteryl ester catabolism. These experiments show that high-density lipoprotein3 cholesteryl esters selectively taken up by hepatocytes are hydrolyzed independently from the classical lysosomal catabolic pathway. The question was addressed if selective uptake mediates a net mass uptake of cholesterol rather than an isotope exchange phenomenon. Incubation of hepatocytes with high-density lipoprotein-3 suppressed endogenous sterol synthesis from sodium [14C]acetate. Hepatocytes were incubated in the presence of high-density lipoprotein3; medium cholesteryl esters decreased as a result of incubation with hepatocytes. These results show a net mass delivery of high-density lipoprotein cholesteryl esters to hepatocytes. In conclusion, the pathway for selective uptake of high-density lipoprotein cholesteryl esters could be demonstrated in human hepatocytes in primary culture. A role for selective uptake in high-density lipoprotein-mediated cholesterol delivery to the liver in human beings in vivo is proposed.