tbuckley/cabot-search huggingface dataset:
Impact of mucolytic treatment on COPD exacerbations
Authors: Usman Farkhutdinov, Valeriy Petryakov, Rafagat Farkhutdinov
Journal: European Respiratory Journal (2013)

Ambroxol (A) is used in the treatment of patients with pulmonary diseases. Apart from mucolytic activity the efficacy of A may be due to its immunomodulatory properties.  The aim was to study the efficacy of A in treatment of patients with chronic obstructive pulmonary disease (COPD).  Methods: The study included 52 patients with exacerbations of COPD. Bronchoalveolar lavage fluid (BALF) obtained during bronchofiberoscopy was examined for the determination of cell composition and immunoglobulins (Ig) concentration. The patients were divided into 2 groups. 25 patients with COPD received standard therapy (antibiotics, bronchodilators, glucocorticosteroids) and A inhalations. The other 27 patients received standard therapy and inhalations with placebo (sodium chloride solution).  Results: In patients with COPD exacerbations the content of alveolar macrophages and the level of Ig in BALF were reduced. The use of A as a part of combined therapy for COPD exacerbation decreased the intensity of clinical symptoms, increased the level of Ig and the content of alveolar macrophages in BALF. In the case of standard therapy disorders in the local immunity and cell composition of BALF were maintained, the duration of exacerbation period was longer.  Conclusion: Ambroxol administration in COPD exacerbations improved the state of local immunity and cell composition of BALF, increased the treatment efficiency.
Response to Letter Regarding Article, “Differential Clinical Outcomes Associated With Hypoglycemia and Hyperglycemia in Acute Myocardial Infarction”
Authors: Abhinav Goyal, Shamir R. Mehta, Hertzel C. Gerstein, Rizwan Afzal, Salim Yusuf, Rafael Díaz, Denis Xavier, Prem Pais, Lisheng Liu
Journal: Circulation (2010)
Early features of acute-on-chronic alcoholic liver failure: a prospective cohort study
Authors: A. Katoonizadeh, W. Laleman, C. Verslype, A. Wilmer, G. Maleux, T. Roskams, F. Nevens
Journal: Gut (2010)

<h3>Background</h3> 'Acute-on-chronic liver failure' (ACLF) is characterised in a more advanced stage by liver failure associated with multiple other end-organ failure. The global clinical characteristics of this entity remain, however, ill-defined. <h3>Objective</h3> To characterise and evaluate the clinicopathological features of patients with ACLF compared with patients with chronic decompensated cirrhosis (CHD) in a prospective, homogeneous cohort of patients with histologically proven alcoholic cirrhosis from 2002 to 2007. <h3>Results</h3> In total 250 patients were screened (ACLF (n=70, 28%) and CHD (n=180, 72%)). Alcoholic liver disease was observed in respectively 61/70 (87%) of patients with ACLF and 72/180 (40%) of patients with CHD. After exclusion of 31 patients, 102 patients were studied: 54 with ACLF (median age 51 years; Child–Pugh 12±2; in-hospital mortality 46% (25/54)) and 48 patients with CHD (median age 53 years; Child–Pugh 10±2; in-hospital mortality 10% (5/48)). In the patients with ACLF who survived the hospital stay, the difference in transplant-free survival compared with patients with CHD tended to attenuate with time. At admission the apparent infection of patient groups was comparable but during hospitalisation infection occurred more frequently in patients with ACLF (31/53 (58%)) than in those with CHD (12/47=26%) (p=0.007). Early signs of infection, positive systemic inflammatory response syndrome (SIRS) criteria at admission and ductular bilirubinostasis (p=0.04), were early features that predicted outcome in ACLF. <h3>Conclusion</h3> Patients with ACLF have a high short-term mortality but those who survived the acute exacerbation show a long-term outcome comparable to that of patients with CHD. Infection is the most common cause of mortality in these patients. Positive SIRS criteria and ductular bilirubinostasis are early markers of ACLF and might allow more rapid identification of high-risk patients.
Elevated Expression of Angiogenin in Prostate Cancer and Its Precursors
Authors: Terrence M. Katona, Blake Lee Neubauer, Philip W. Iversen, Shaobo Zhang, Lee Ann Baldridge, Liang Cheng
Journal: Clinical Cancer Research (2005)

Abstract Purpose: Angiogenin is a polypeptide involved in the formation and establishment of new blood vessels necessary for growth and metastasis of numerous malignant neoplasms, including prostatic adenocarcinoma. Antiangiogenin therapy inhibits the establishment, growth, and metastasis of prostatic adenocarcinoma in animal studies. In this study, we have investigated the expression of angiogenin in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostatic epithelium in a large cohort of prostatectomy specimens. Methods: We have studied the expression of angiogenin by immunohistochemistry in prostatic adenocarcinoma, high-grade prostatic intraepithelial neoplasia, and adjacent benign prostatic tissue in 107 human total prostatectomy specimens. Results: The percentage of cells staining positively for angiogenin in benign prostatic glandular epithelium (mean = 17%) was significantly less than for high-grade prostatic intraepithelial neoplasia (mean = 58%, P &amp;lt; 0.001) and prostatic adenocarcinoma (mean = 60%, P &amp;lt; 0.001). Compared with adjacent benign prostatic epithelium, the staining intensity was significantly greater in high-grade prostatic intraepithelial neoplasia (P &amp;lt; 0.001) and prostatic adenocarcinoma (P &amp;lt; 0.001). Furthermore, staining intensity has significantly stronger in prostatic adenocarcinoma versus high-grade prostatic intraepithelial neoplasia (P = 0.0023). However, there was no correlation of angiogenin expression with various clinical and pathologic variables examined, including age at surgery, Gleason scores, pathologic stage, tumor extent, angiolymphatic invasion, extraprostatic extension, seminal vesical invasion, lymph node metastasis, surgical margin status, presence of prostatic intraepithelial neoplasia, and perineural invasion. Conclusion: Angiogenin expression in prostatic tissue increases as prostatic epithelial cells evolve from a benign to an invasive phenotype. The increasing expression of prostatic adenocarcinoma in the progression from benign prostate to high-grade prostatic intraepithelial neoplasia and ultimately to prostatic adenocarcinoma are consistent with previous studies showing the influential role that angiogenin plays in the growth, invasion, and metastasis of prostatic adenocarcinoma and many other malignant tumors.
Catheter-Related Deep Venous Thrombosis and Other Catheter Complications in Children With Cancer
Authors: Janna M. Journeycake, George R. Buchanan
Journal: Journal of Clinical Oncology (2006)

Asymptomatic deep vein thrombosis (DVT) is a complication of central venous catheter (CVC) use in children with cancer, but its clinical significance is not well defined. Children with CVCs commonly experience two other CVC-related complications: occlusion and infection. The aim of this study was to determine the frequency of these two complications and their association with DVT.We conducted a retrospective cohort study of patients who were diagnosed with cancer. Data collected included number and type of catheter insertions, duration of use, reason for removal, associated catheter complications, and demographic information.Catheters were placed in 287 patients for a total of 128,403 days (mean, 290 +/- 269 days/catheter). Of 21 patients (7%) diagnosed with CVC-related DVT, only five had specific signs or symptoms. Nineteen (90%) of these 21 children had prior history of catheter occlusion, and 10 of the 19 also experienced infection. Ten children (48%) were not identified as having DVT until they had had multiple catheters with recurrent complications. Odds of having DVT were higher in patients who had a single catheter complicated by repeated occlusions (odds ratio [OR], 3.7; P = .001) or infection (OR, 2.2; P = .016). Patients experiencing both infection and occlusion were at 6.4 times (P < .0001) higher risk of developing DVT.Children with CVC-related DVT frequently have recurrent catheter complications. Unrecognized thrombosis may therefore be clinically important. Prospective studies are needed to determine if identification and treatment of occult DVT will prevent additional CVC-related complications and prolong the duration of catheter use.
CXCL12/SDF‐1α Activates NF‐κB and Promotes Oral Cancer Invasion through the Carma3/Bcl10/Malt1 Complex
Authors: Aasia O Rehman, Cun‐yu Wang
Journal: International Journal of Oral Science (2009)

To determine how SDF‐1α/CXCR4 activates nuclear factor‐kappa B (NF‐κB) and promotes oral squamous cell carcinoma (OSCC) invasion. A lentivirus‐based knockdown approach was utilized to deplete gene expression. NF‐κB activation was evaluated by Western blot analysis and electrophoretic mobility shift (EMSA). We show that the activation of NF‐κB by CXCR4 occurs through the Carma3/Bcl10/Malt1 (CBM) complex in OSCC. We found that loss of components of the CBM complex in HNSCC can inhibit SDF‐1α induced phosphorylation and degradation of IκBα, while TNFα induced IKK activation remains unchanged. Further, we identified a role for novel and atypical, but not classical, PKCs in activating IKK through CXCR4. Importantly, inhibition of the CBM complex leads to a significant decrease in SDF‐1α mediated invasion of OSCC. The CBM complex plays a critical role in CXCR4‐induced NF‐κB activation in OSCC. Targeting molecular components of the NF‐κB signaling pathway may provide an important therapeutic opportunity in controlling the progression and metastasis of OSCC mediated by SDF‐1α.
Heat-Shock Induction of Tumor-Derived Danger Signals Mediates Rapid Monocyte Differentiation into Clinically Effective Dendritic Cells
Authors: Raquel Aguilera, Carlos Saffie, Andrés Tittarelli, Fermín E. González, Marcos Ramírez, Diego Reyes, Cristián Pereda, Daniel Hevia, Tamara García, Lorena Salazar, Arturo Ferreira, Marcela Hermoso, Ariadna Mendoza-Naranjo, Carlos Ferrada, Paola Garrido, Mercedes N. López, Flavio Salazar-Onfray
Journal: Clinical Cancer Research (2011)

This study characterizes, biologically and clinically, a novel type of dendritic cells (DC) produced in the short term and called tumor antigen-presenting cells (TAPCells). In particular, we identified factors present in a lysate derived from heat-shocked allogeneic melanoma cells (TRIMEL) that are associated with TAPCells' enhanced capability to induce CD8(+) T-cell responses in vitro and in vaccinated melanoma patients.First, extensive phenotypic and functional characterization of TAPCells was performed, followed by vaccination of 45 melanoma patients with four doses of TAPCells over a period of 2 months. Specific delayed-type hypersensitivity (DTH) reaction was analyzed posttreatment and correlated with overall survival rates. Furthermore, heat-shock (HS)-induced factors present in TRIMEL and their effects on DC activation were identified and studied.TRIMEL induced a committed, mature, DC-like phenotype in TAPCells and effectively activated melanoma-specific CD4(+) and CD8(+) T cells. Clinically, 64% of vaccinated patients showed positive DTH reaction against TRIMEL, and this was associated with improved overall survival. HS treatment of tumor cells increased calreticulin (CRT) plasma membrane translocation and induced the release of high-mobility group box 1 proteins (HMGB1). Both CRT and HMGB1 mobilization were associated with enhanced TAPCells' maturation and antigen (Ag) cross-presentation, respectively. DTH infiltration analysis revealed the presence of CD8(+)/CD45RO(+) T cells, thus confirming TAPCells' ability to cross-present Ags in vivo.Our results indicate that lysates derived from heat-shocked tumor cells are an optimal source of tumor-associated Ags, which are crucial for the generation of DCs with improved Ag cross-presentation capacity and clinically effective immunogenicity.
Soluble complement receptor type 1 (CD35) in bronchoalveolar lavage of inflammatory lung diseases
Authors: J Hamacher, S Sadallah, JA Schifferli, J Villard, LP Nicod
Journal: European Respiratory Journal (1998)

Complement receptor type 1 (CR1) (CD35; C3b/C4b receptor) is a transmembrane protein of many haematopoietic cells. Once cleaved, soluble complement receptor type 1 (sCR1) exerts opposite effects as a powerful inhibitor of complement. This study addressed both the question of whether sCR1 was found in bronchoalveolar lavage (BAL) of normals and patients with various inflammatory disease, and its possible origin. In this retrospective study covering specimen and clinical data of 124 patients with acute and chronic inflammatory lung pathologies, BAL supernatants were analysed by enzyme-linked immunosorbent assay technique for sCR1. Correlations were made between the sCR1 levels obtained and the constituents of BAL. Human alveolar macrophages were cultivated in order to determine their secretory capacity of sCR1. Alveolar macrophages from normal subjects were shown to release sCR1 in vitro. In addition, sCR1 was present in BAL of normal controls and was significantly increased in acute inflammatory lung diseases such as acute respiratory distress syndrome (ARDS), bacterial and Pneumocystis carinii pneumonia, as well as in chronic inflammatory diseases such as interstitial lung fibrosis and sarcoidosis. In BAL of ARDS, bacterial, and P. carinii pneumonia, there was a good correlation between sCR1 and the absolute neutrophil counts. In sarcoidosis, a correlation was found with BAL lymphocyte counts. Serum sCR1 was not increased in patients compared to controls. Soluble complement receptor type 1 (sCR1) is found in the bronchoalveolar lavage in health as well as in acute and chronic inflammatory disease. Alveolar macrophages are capable of releasing sCR1 in vitro and may be the main physiological source of sCR1 in the alveoli. The good correlation between sCR1 and the absolute neutrophil or lymphocyte numbers in bronchoalveolar lavage of inflammatory diseases suggests a predominant role of leucocytes for the release of sCR1 in such conditions. The release of this inhibitor of complement may be crucial to control and reduce complement activation and thus prevent lung injury.
Screening for Lung Cancer with Low-Dose Spiral Computed Tomography
Authors: STEPHEN J. SWENSEN, JAMES R. JETT, JEFF A. SLOAN, DAVID E. MIDTHUN, THOMAS E. HARTMAN, ANNE-MARIE SYKES, GREGORY L. AUGHENBAUGH, FRANK E. ZINK, SHAUNA L. HILLMAN, GAYLE R. NOETZEL, RANDOLPH S. MARKS, AMY C. CLAYTON, PETER C. PAIROLERO
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

Studies suggest that screening with spiral computed tomography can detect lung cancers at a smaller size and earlier stage than chest radiography can. To evaluate low-radiation-dose spiral computed tomography and sputum cytology in screening for lung cancer, we enrolled 1,520 individuals aged 50 yr or older who had smoked 20 pack-years or more in a prospective cohort study. One year after baseline scanning, 2,244 uncalcified lung nodules were identified in 1,000 participants (66%). Twenty-five cases of lung cancer were diagnosed (22 prevalence, 3 incidence). Computed tomography alone detected 23 cases; sputum cytology alone detected 2 cases. Cell types were: squamous cell, 6; adenocarcinoma or bronchioalveolar, 15; large cell, 1; small cell, 3. Twenty-two patients underwent curative surgical resection. Seven benign nodules were resected. The mean size of the non-small cell cancers detected by computed tomography was 17 mm (median, 13 mm). The postsurgical stage was IA, 13; IB, 1; IIA, 5; IIB, 1; IIIA, 2; limited, 3. Twelve (57%) of the 21 non-small cell cancers detected by computed tomography were stage IA at diagnosis. Computed tomography can detect early-stage lung cancers. The rate of benign nodule detection is high.
Functional annotation of the human brain methylome identifies tissue-specific epigenetic variation across brain and blood
Authors: Matthew N Davies, Manuela Volta, Ruth Pidsley, Katie Lunnon, Abhishek Dixit, Simon Lovestone, Cristian Coarfa, R Alan Harris, Aleksandar Milosavljevic, Claire Troakes, Safa Al-Sarraj, Richard Dobson, Leonard C Schalkwyk, Jonathan Mill
Journal: Genome biology (2012)

Abstract Background Dynamic changes to the epigenome play a critical role in establishing and maintaining cellular phenotype during differentiation, but little is known about the normal methylomic differences that occur between functionally distinct areas of the brain. We characterized intra- and inter-individual methylomic variation across whole blood and multiple regions of the brain from multiple donors. Results Distinct tissue-specific patterns of DNA methylation were identified, with a highly significant over-representation of tissue-specific differentially methylated regions (TS-DMRs) observed at intragenic CpG islands and low CG density promoters. A large proportion of TS-DMRs were located near genes that are differentially expressed across brain regions. TS-DMRs were significantly enriched near genes involved in functional pathways related to neurodevelopment and neuronal differentiation, including BDNF , BMP4 , CACNA1A , CACA1AF , EOMES , NGFR , NUMBL , PCDH9 , SLIT1 , SLITRK1 and SHANK3 . Although between-tissue variation in DNA methylation was found to greatly exceed between-individual differences within any one tissue, we found that some inter-individual variation was reflected across brain and blood, indicating that peripheral tissues may have some utility in epidemiological studies of complex neurobiological phenotypes. Conclusions This study reinforces the importance of DNA methylation in regulating cellular phenotype across tissues, and highlights genomic patterns of epigenetic variation across functionally distinct regions of the brain, providing a resource for the epigenetics and neuroscience research communities.
Health Care Costs in People With Diabetes and Their Association With Glycemic Control and Kidney Function
Authors: Kerry A. McBrien, Braden J. Manns, Betty Chui, Scott W. Klarenbach, Doreen Rabi, Pietro Ravani, Brenda Hemmelgarn, Natasha Wiebe, Flora Au, Fiona Clement
Journal: Diabetes Care (2012)

To determine the association between laboratory-derived measures of glycemic control (HbA1c) and the presence of renal complications (measured by proteinuria and estimated glomerular filtration rate [eGFR]) with the 5-year costs of caring for people with diabetes.We estimated the cumulative 5-year cost of caring for people with diabetes using a province-wide cohort of adults with diabetes as of 1 May 2004. Costs included physician visits, hospitalizations, ambulatory care (emergency room visits, day surgery, and day medicine), and drug costs for people >65 years of age. Using linked laboratory and administrative clinical and costing data, we determined the association between baseline glycemic control (HbA1c), proteinuria, and kidney function (eGFR) and 5-year costs, controlling for age, socioeconomic status, duration of diabetes, and comorbid illness.We identified 138,662 adults with diabetes. The mean 5-year cost of diabetes in the overall cohort was $26,978 per patient, excluding drug costs. The mean 5-year cost for the subset of people >65 years of age, including drug costs, was $44,511 (Canadian dollars). Cost increased with worsening kidney function, presence of proteinuria, and suboptimal glycemic control (HbA1c >7.9%). Increasing age, Aboriginal status, socioeconomic status, duration of diabetes, and comorbid illness were also associated with increasing cost.The cost of caring for people with diabetes is substantial and is associated with suboptimal glycemic control, abnormal kidney function, and proteinuria. Future studies should assess if improvements in the management of diabetes, assessed with laboratory-derived measurements, result in cost reductions.
Empathy: Common sense, science sense, wolves, and well-being
Authors: Marc Bekoff
Journal: Behavioral and Brain Sciences (2002)

Empathy is likely more widely distributed among animals than many researchers realize or perhaps are willing to admit. Studies of social carnivores, other group-living animals, and communication via different modalities will help us learn more about the evolutionary roots and behavioral, sensory, and cognitive underpinnings of empathy, including what it means to have a sense of self. There are also important implications for debates about animal well-being.
The C161→T polymorphism in peroxisome proliferator–activated receptor gamma, but not P12A, is associated with insulin resistance in Hispanic and non-Hispanic white women: evidence for another functional variant in peroxisome proliferator–activated receptor gamma
Authors: Susan P. Moffett, Eleanor Feingold, M. Michael Barmada, Coleen M. Damcott, Julie A. Marshall, Richard F. Hamman, Robert E. Ferrell
Journal: Metabolism (2005)
Prostaglandin E2 promotes survival of naive UCB T cells via the Wnt/β-catenin pathway and alters immune reconstitution after UCBT
Authors: L Li, H T Kim, A Nellore, N Patsoukis, V Petkova, S McDonough, I Politikos, S Nikiforow, R Soiffer, J H Antin, K Ballen, C Cutler, J Ritz, V A Boussiotis
Journal: Blood Cancer Journal (2014)

The outcome of umbilical cord blood transplantation (UCBT) is compromised by low hematopoietic stem cell (HSC) doses leading to prolonged time to engraftment, delayed immunological reconstitution and late memory T-cell skewing. Exposure of UCB to dimethyl-prostaglandin E2 (dmPGE2) increases HSC in vivo. We determined that exposure of UCB T lymphocytes to dmPGE2 modified Wnt signaling resulting in T cell factor (TCF)-mediated transcription. Wnt signaling upregulated interleukin (IL)-7R and IL-2Rβ, resulting in enhanced survival mediated by the homeostatic cytokines IL-7 and IL-15. dmPGE2 also induced components of the Wnt pathway and Wnt receptors, thereby priming UCB T cells to receive signals via Wnt ligands in vivo. We observed that the Wnt transcription factor TCF7 and its target EOMES were elevated in the T cells of patients who received PGE2-treated UCBs. Consistent with the role of Wnt/β-catenin signaling to induce and maintain naive, memory precursors and long-lived central memory CD8(+) cells, these patients also had increased fractions of CD8(+)CD45RO(-)CD62L(+) plus CD8(+)CD45RO(+)CD62L(+) subsets encompassing these T-cell populations. These effects of the PGE2/Wnt/β-catenin axis may have significant implications for harnessing immunity in the context of UCBT, where impaired immune reconstitution is associated with late memory T-cell skewing.
Formation of cholesteryl ester-rich particulate lipid during metabolism of chylomicrons
Authors: T. G. Redgrave
Journal: Journal of Clinical Investigation (1970)

The metabolism of chylomicrons doubly labeled with cholesterol-3H and triglyceride-14C was studied in unanesthetized rats which were absorbing a fatty test meal. 10 min after intravenous injection, 80% of chylomicron cholesteryl ester, but only 20% of chylomicron triglyceride, was found in the liver. Treatment of recipient rats with puromycin to block hepatic triglyceride release did not increase the proportion of chylomicron triglyceride found in the liver.
Considering Options for Attenuating Postmeal Glucose Excursions
Authors: Judith Wylie-Rosett, Carmen R. Isasi
Journal: Diabetes Care (2010)

Attenuating postmeal blood glucose excursions is a clinical challenge. While strategies for modifying the quantity and quality of carbohydrate consumed are widely used to reduce postprandial blood glucose peaks, we have paid relatively little attention to how premeal snacks and their composition may alter meal responses. In this issue, Chen et al. (1) reported that feeding a snack of soybeans (30 g) and yogurt (75 g) 2 h before breakfast lowered the post-breakfast blood glucose excursion by 40%. While their article did not provide the macronutrient composition of the snack, it was described as a high-protein, low-carbohydrate snack.

Chen et al. (1) appear to attribute the glycemic effects of the soy-yogurt primer to its high-protein, low-carbohydrate composition. However, they also mention that the suppression of …