tbuckley/cabot-search huggingface dataset:
Maximal neutropenia during chemotherapy and radiotherapy is significantly associated with the development of acute radiation-induced dysphagia in lung cancer patients
Authors: D. De Ruysscher, C. Dehing, R.-H. Bremer, S.M. Bentzen, F. Koppe, M. Pijls-Johannesma, L. Harzée, A. Minken, R. Wanders, M. Hochstenbag, A.-M. Dingemans, L. Boersma, E. van Haren, W. Geraedts, C. Pitz, J. Simons, B.G. Wouters, J.-F. Rosier, P. Lambin
Journal: Annals of Oncology (2007)
Drug interactions of the newer oral antifungal agents
Authors: None Katz
Journal: British Journal of Dermatology (1999)

The newer oral antifungal agents, such as fluconazole, itraconazole and terbinafine, are generally both effective and well tolerated in the management of widespread or resistant dermatomycoses such as onychomycosis. However, these agents differ markedly in their potential to cause clinically significant drug interactions. Triazoles such as fluconazole and itraconazole have been responsible for a greater number of clinically significant drug interactions than terbinafine. For example, itraconazole, and to a lesser extent fluconazole (in high doses) are inhibitors of CYP3A4. Therefore certain agents that are substrates of this enzyme, such as some of the new generation of H1-antihistamines, several HMG-CoA reductase inhibitors and certain benzodiazepines, are contraindicated. Other drugs like cyclosporine and quinidine need careful monitoring if administered concurrently with these triazoles. In contrast, there are no drug-drug contraindications with terbinafine. Indeed, in a postmarketing surveillance study, in which 42.8% of the 25,884 participating patients were taking a variety of concomitant therapies, no new drug-drug interactions were revealed. Physicians should be aware of the potential for interaction of the medications that they prescribe, in order to prevent or reduce the burden of adverse events. Terbinafine may be the most rational choice of oral antifungal agent in patients receiving concomitant medications that may adversely affect or be affected by either fluconazole or itraconazole.
The Gut Microbiome, Kidney Disease, and Targeted Interventions
Authors: Ali Ramezani, Dominic S. Raj
Journal: Journal of the American Society of Nephrology (2013)

The human gut harbors >100 trillion microbial cells, which influence the nutrition, metabolism, physiology, and immune function of the host. Here, we review the quantitative and qualitative changes in gut microbiota of patients with CKD that lead to disturbance of this symbiotic relationship, how this may contribute to the progression of CKD, and targeted interventions to re-establish symbiosis. Endotoxin derived from gut bacteria incites a powerful inflammatory response in the host organism. Furthermore, protein fermentation by gut microbiota generates myriad toxic metabolites, including p-cresol and indoxyl sulfate. Disruption of gut barrier function in CKD allows translocation of endotoxin and bacterial metabolites to the systemic circulation, which contributes to uremic toxicity, inflammation, progression of CKD, and associated cardiovascular disease. Several targeted interventions that aim to re-establish intestinal symbiosis, neutralize bacterial endotoxins, or adsorb gut-derived uremic toxins have been developed. Indeed, animal and human studies suggest that prebiotics and probiotics may have therapeutic roles in maintaining a metabolically-balanced gut microbiota and reducing progression of CKD and uremia-associated complications. We propose that further research should focus on using this highly efficient metabolic machinery to alleviate uremic symptoms.
Homologous Recombination between Highly Diverged Mitochondrial Sequences: Examples from Maternally and Paternally Transmitted Genomes
Authors: E. D. Ladoukakis, I. Theologidis, G. C. Rodakis, E. Zouros
Journal: Molecular Biology and Evolution (2011)

Homologous recombination is restricted to sequences of low divergence. This is attributed to the mismatch repairing system (MMR), which does not allow recombination between sequences that are highly divergent. This acts as a safeguard against recombination between nonhomologous sequences that could result in genome imbalance. Here, we report recombination between maternal and paternal mitochondrial genomes of the sea mussel, whose sequences differ by >20%. We propose that the strict maternal inheritance of the animal mitochondrial DNA and the ensuing homoplasmy has relieved the MMR system of the animal mitochondrion from the pressure to tolerate recombination only among sequences with a high degree of similarity.
9-<i>O</i>-Acetylation of Sialomucins: A Novel Marker of Murine CD4 T Cells that Is Regulated during Maturation and Activation
Authors: Murli Krishna, Ajit Varki
Journal: The Journal of Experimental Medicine (1997)

Terminal sialic acids on cell surface glycoconjugates can carry 9-O-acetyl esters. For technical reasons, it has previously been difficult to determine their precise distribution on different cell types. Using a recombinant soluble form of the Influenza C virus hemagglutinin-esterase as a probe for 9-O-acetylated sialic acids, we demonstrate here their preferential expression on the CD4 T cell lineage in normal B10.A mouse lymphoid organs. Of total thymocytes, 8–10% carry 9-O-acetylation; the great majority of these are the more mature PNA−, HSA−, and TCRhi medullary cells. While low levels of 9-O-acetylation are seen on some CD4/CD8 double positive (DP) and CD8 single positive (SP) cells, high levels are present primarily on 80– 85% of CD4 SP cells. Correlation with CD4 and CD8 levels suggests that 9-O-acetylation appears as an early differentiation marker as cells mature from the DP to the CD4 SP phenotype. This high degree of 9-O-acetylation is also present on 90–95% of peripheral spleen and lymph node CD4 T cells. In contrast, only a small minority of CD8 T cells and B cells show such levels of 9-O-acetylation. Among mature peripheral CD4 T lymphocytes, the highly O-acetylated cells are Mel 14hi, CD44lo, and CD45R(exon B)hi, features typical of naive cells. Digestions with trypsin and O-sialoglycoprotease (OSGPase) and ELISA studies of lipid extracts indicate that the 9-O-acetylated sialic acids on peripheral CD4 T cells are predominantly on O-linked mucintype glycoproteins and to a lesser degree, on sialylated glycolipids (gangliosides). In contrast, sialic acids on mucin type molecules of CD8 T cells are not O-acetylated; instead these molecules mask the recognition of O-acetylated gangliosides that seem to be present at similar levels as on CD4 cells. The 9-O-acetylated gangliosides on mouse T cells are not bound by CD60 antibodies, which recognize O-acetylated gangliosides in human T cells. Tethering 9-O-acetylated mucins with the Influenza C probe with or without secondary cross-linking did not cause activation of CD4 T cells. However, activation by other stimuli including TCR ligation is associated with a substantial decrease in surface 9-O-acetylation, primarily in the mucin glycoprotein component. Thus, 9-O-acetylation of sialic acids on cell surface mucins is a novel marker on CD4 T cells that appears on maturation and is modulated downwards upon activation.
Hydroxystearic acid and diarrhoea following ileal resection
Authors: H. S. Wiggins, J. H. Cummings, J. R. Pearson
Journal: Gut (1974)

The faecal outputs of 10 patients who complained of diarrhoea after ileal resection were measured whilst they consumed identical diets in which most of the fat was present as olive oil. No relationship was found between faecal weight and hydroxystearic acid production. In three patients the output of hydroxystearic acid was reduced by changing the dietary fat. There was no reduction in faecal weight. It is concluded that hydroxystearic acid does not contribute to diarrhoea in these cases.
Systematic Review of Methods for Reporting Combined Outcomes After Radical Prostatectomy and Proposal of a Novel System: The Survival, Continence, and Potency (SCP) Classification
Authors: Vincenzo Ficarra, Prasanna Sooriakumaran, Giacomo Novara, Oscar Schatloff, Alberto Briganti, Henk Van der Poel, Francesco Montorsi, Vip Patel, Ashutosh Tewari, Alexander Mottrie
Journal: European Urology (2011)
Monitoring of the Respiratory Muscles in the Critically Ill
Authors: Jonne Doorduin, Hieronymus W. H. van Hees, Johannes G. van der Hoeven, Leo M. A. Heunks
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Evidence has accumulated that respiratory muscle dysfunction develops in critically ill patients and contributes to prolonged weaning from mechanical ventilation. Accordingly, it seems highly appropriate to monitor the respiratory muscles in these patients. Today, we are only at the beginning of routinely monitoring respiratory muscle function. Indeed, most clinicians do not evaluate respiratory muscle function in critically ill patients at all. In our opinion, however, practical issues and the absence of sound scientific data for clinical benefit should not discourage clinicians from having a closer look at respiratory muscle function in critically ill patients. This perspective discusses the latest developments in the field of respiratory muscle monitoring and possible implications of monitoring respiratory muscle function in critically ill patients.
Magnetic Resonance Diffusion as Predictive Value of Response to Treatment with Chemo-Radiotherapy in Patients with Locally Advanced Rectal Cancer
Authors: Gallego Jimenez Inmaculada, Rico Gala Susana, López-Ladrón Amelia, M. Fernández-Parra Eva, Morales Pancorbo David, Salvador Bofill Francisco Javier
Journal: Annals of Oncology (2014)
The Unenlarged Lymph Nodes of HIV-1–infected, Asymptomatic Patients with High CD4 T Cell Counts Are Sites for Virus Replication and CD4 T Cell Proliferation. The Impact of Highly Active Antiretroviral Therapy
Authors: Klara Tenner-Racz, Hans-Jürgen Stellbrink, Jan van Lunzen, Claus Schneider, Jan-Peter Jacobs, Birgit Raschdorff, Gudrun Großschupff, Ralph M. Steinman, Paul Racz
Journal: The Journal of Experimental Medicine (1998)

The efficacy of triple drug therapy for HIV-1 infection encourages its early use to prevent damage to the immune system. We monitored the effects of such therapy on 12 patients with 14–75-mo histories of minimal disease, i.e., CD4+ counts constantly &amp;gt;500/μl and little or no lymph node enlargement. In this way, we could first determine the extent of viral replication and immunoarchitectural changes in unenlarged nodes early in disease, and second follow the response to triple therapy in plasma and lymphoid tissue in tandem. As is known for lymph nodes with more advanced disease, the germinal centers showed productively infected T cells, i.e., CD4+CD1a−CD68− cells labeling intensely for HIV-1 RNA after in situ hybridization. The unenlarged nodes also showed extensive HIV-1 RNA retention on a well-preserved, follicular dendritic cell (FDC) network, and the follicles were abnormal. There were numerous CD8+ cells, many expressing TIA-1 granule antigen. Also, in contrast to normal follicles, CD4+ T cell proliferation was active, with marked increases in the number of cycling, Ki-67+CD4+CD45R0+ cells. After 28 d and 3 mo of therapy, productively infected T cells decreased dramatically and often were not apparent. The labeling of the FDC network for viral RNA also decreased, but not for gag protein. We conclude that HIV-1 replicates and accumulates in lymphoid organs before damage of the immune system, that at this stage of disease de novo production of T cells occurs in the lymphoid tissue, and that the infection is sensitive to triple drug therapy in both plasma and lymph nodes.
Serologic Studies on Cells of Graffi Virus-Induced Myeloid Leukemia in Mice
Authors: Günter Pasternak
Journal: JNCI Journal of the National Cancer Institute (1965)

Sera of mice resistant to isologous inocula of Graffi virus-induced myeloid leukemias reacted in vitro with cells of leukemias having the same viral origin. Specific humoral antibodies were detected by the indirect fluorescent-antibody and cytotoxic tests. Antibody activity was removed by absorption of the immune sera with Graffi leukemia cells. Normal spleen and lymph node cells and cells of a spontaneous AKR leukemia did not absorb the activity directed against Graffi leukemia cells. The immune sera possessed virus-neutralizing capacity as indicated by the inactivation of a virus-containing, cell-free leukemia filtrate. Formation of antibodies reacting with leukemia cells was also induced by inoculation of adult mice both with active and formalin-treated preparations of the Graffi virus. Whether the specific antigen of the leukemia cells could represent an antigen present in the virus is discussed.
Expression, Cellular Distribution, and Prognostic Relevance of TRAIL Receptors in Hepatocellular Carcinoma
Authors: Lydia Kriegl, Andreas Jung, Jutta Engel, Rene Jackstadt, Alexander L. Gerbes, Eike Gallmeier, Jana A. Reiche, Heiko Hermeking, Antonia Rizzani, Christiane J. Bruns, Frank T. Kolligs, Thomas Kirchner, Burkhard Göke, Enrico N. De Toni
Journal: Clinical Cancer Research (2010)

After the advent of targeted therapies for hepatocellular carcinoma (HCC), much work is being done to provide a comprehensive description of the different signaling pathways contributing to cell survival and proliferation in this tumor. Apoptotic signaling mediated by tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) represents an important mechanism of tumor surveillance, but its importance in the development of HCC is not known. We thus investigated the cellular distribution and the prognostic importance of TRAIL receptors in HCC.Immunohistochemical staining for TRAIL receptors was evaluated in HCC tissues and in matched surrounding nontumor tissues of 157 HCC patients treated with liver transplantation or partial hepatectomy. Survival was analyzed in 93 patients who underwent partial hepatectomy.The fraction of HCC samples with positive membrane staining for TRAIL receptor 1 (TRAIL-R1) and 2 (TRAIL-R2) was 1.4- and 2.7-fold lower compared with that of hepatocytes from surrounding tissues (P = 0.01). Loss of either TRAIL-R1 or TRAIL-R2, as confirmed by a multivariate analysis, significantly worsened 5-year survival of HCC patients {survival, 27% versus 52% and 15% versus 43%; hazard ratio (HR), 2.3 [95% confidence interval (CI), 1.1-4.4] and 2.4 (95% CI, 1.1-5.2), respectively}. Loss of both TRAIL receptors further decreased survival of patients [HR, 5.72 (95% CI, 2.1-15.5) versus double-negative staining; P = 0.001], indicating an additive effect on survival of TRAIL-R1 and TRAIL-R2.This pilot study suggests that loss of TRAIL receptors is a frequent feature of HCCs and an independent predictor of survival in patients undergoing partial hepatectomy. Future therapeutic protocols are likely to profit from the characterization of their expression and cellular distribution. Clin Cancer Res; 16(22); 5529-38. ©2010 AACR.
Clusterin is up-regulated in glomerular mesangial cells in complement-mediated injury
Authors: Koei Yamada, Yuichi Hori, Norio Hanafusa, Toshihiro Okuda, Nobuo Nagano, Nam-Ho Choi-Miura, William G. Couser, Toshio Miyata, Kiyoshi Kurokawa, Toshiro Fujita, Masaomi Nangaku
Journal: Kidney International (2001)
Cross-Sectional Relations of Multiple Biomarkers From Distinct Biological Pathways to Brachial Artery Endothelial Function
Authors: Sekar Kathiresan, Philimon Gona, Martin G. Larson, Joseph A. Vita, Gary F. Mitchell, Geoffrey H. Tofler, Daniel Levy, Christopher Newton-Cheh, Thomas J. Wang, Emelia J. Benjamin, Ramachandran S. Vasan
Journal: Circulation (2006)

Endothelial dysfunction is a critical intermediate phenotype in the pathogenesis of cardiovascular disease. We evaluated the relative contributions of distinct biological pathways to interindividual variation in endothelial function by relating prototype biomarkers (representing these pathways) to brachial artery vasodilator function.We investigated the cross-sectional relations of a panel of 7 biomarkers measured at a routine examination to brachial artery vasodilator function (flow-mediated dilation [FMD] and reactive hyperemia) assessed at a subsequent examination (mean interval, 2.9 years) in 2113 Framingham Heart Study participants (mean age, 61 years; 54% women). We selected biomarkers from 4 biological domains: neurohormonal (N-terminal pro-atrial natriuretic peptide [N-ANP], B-type natriuretic peptide [BNP], renin, aldosterone), hemostatic factors (plasminogen activator inhibitor-1 [PAI-1]), inflammation (C-reactive protein [CRP]), and target organ damage (urine albumin-creatinine ratio). In age- and sex-adjusted models, several biomarkers were related to baseline brachial artery diameter (PAI-1, CRP, urine albumin-creatinine ratio), baseline mean flow (N-ANP, BNP, PAI-1, CRP, aldosterone), FMD (N-ANP, PAI-1, CRP, renin), and reactive hyperemia (BNP, PAI-1, CRP, renin, urine albumin-creatinine ratio). In multivariable analyses relating the 7 biomarkers conjointly to each vascular function measure (adjusting for known risk factors), N-ANP and renin were positively related to FMD (P=0.001 and P=0.04, respectively), and N-ANP was inversely related to baseline mean flow velocity (P=0.01). None of the other biomarkers was significantly related to the vascular function measures studied.In our large community-based sample, a conservative strategy relating several biomarkers to vascular endothelial function identified plasma N-ANP as a key correlate of mean flow under basal conditions and of FMD in response to forearm cuff occlusion.
Novel Metabolic Markers for the Risk of Diabetes Development in American Indians
Authors: Jinying Zhao, Yun Zhu, Noorie Hyun, Donglin Zeng, Karan Uppal, ViLinh T. Tran, Tianwei Yu, Dean Jones, Jiang He, Elisa T. Lee, Barbara V. Howard
Journal: Diabetes Care (2014)

To identify novel metabolic markers for diabetes development in American Indians.Using an untargeted high-resolution liquid chromatography-mass spectrometry, we conducted metabolomics analysis of study participants who developed incident diabetes (n = 133) and those who did not (n = 298) from 2,117 normoglycemic American Indians followed for an average of 5.5 years in the Strong Heart Family Study. Relative abundances of metabolites were quantified in baseline fasting plasma of all 431 participants. Prospective association of each metabolite with risk of developing type 2 diabetes (T2D) was examined using logistic regression adjusting for established diabetes risk factors.Seven metabolites (five known and two unknown) significantly predict the risk of T2D. Notably, one metabolite matching 2-hydroxybiphenyl was significantly associated with an increased risk of diabetes, whereas four metabolites matching PC (22:6/20:4), (3S)-7-hydroxy-2',3',4',5',8-pentamethoxyisoflavan, or tetrapeptides were significantly associated with decreased risk of diabetes. A multimarker score comprising all seven metabolites significantly improved risk prediction beyond established diabetes risk factors including BMI, fasting glucose, and insulin resistance.The findings suggest that these newly detected metabolites may represent novel prognostic markers of T2D in American Indians, a group suffering from a disproportionately high rate of T2D.
Pathophysiology and Treatment of Sleep Apnea
Authors: D H Ingbar, J B L Gee
Journal: Annual Review of Medicine (1985)

The sleep apnea syndromes have attracted the interest of physicians and scientists in many different disciplines because the disorders involve the physiology of sleep, the control of respiration, the function of the upper airway, and the clinical sequelae upon cardiac, pulmonary, and psychological function. Over the eight years since this subject was last reviewed here (1), the pathophysiology of obstructive sleep apnea has become better understood. A variety of new treatments are now available. However, our clinical knowledge of the syndrome and its natural history have changed little. The high prevalence of these syndromes and related disorders such as snoring is only beginning to be apparent. This chapter reviews current understanding of these syndromes, with particular emphasis on recent advances, and highlights questions for future investigation. First, we consider normal upper airway function and the control of breathing during sleep. Then, we apply this information to a consideration of the pathophysiology, clinical features, and treatment of sleep apnea syndromes.
The occupational burden of chronic obstructive pulmonary disease
Authors: L. Trupin, G. Earnest, M. San Pedro, J.R. Balmes, M.D. Eisner, E. Yelin, P.P. Katz, P.D. Blanc
Journal: European Respiratory Journal (2003)

Although chronic obstructive pulmonary disease (COPD) is attributed predominantly to tobacco smoke, occupational exposures are also suspected risk factors for COPD. Estimating the proportion of COPD attributable to occupation is thus an important public health need. A randomly selected sample of 2,061 US residents aged 55-75 yrs completed telephone interviews covering respiratory health, general health status and occupational history. Occupational exposure during the longest-held job was determined by self-reported exposure to vapours, gas, dust or fumes and through a job exposure matrix. COPD was defined by self-reported physician's diagnosis. After adjusting for smoking status and demography, the odds ratio for COPD related to self-reported occupational exposure was 2.0 (95% confidence interval (CI) 1.6-2.5), resulting in an adjusted population attributable risk (PAR) of 20% (95% CI 13-27%). The adjusted odds ratio based on the job exposure matrix was 1.6 (95% CI 1.1-2.5) for high and 1.4 (95% CI 1.1-1.9) for intermediate probability of occupational dust exposure; the associated PAR was 9% (95% CI 3-15%). A narrower definition of COPD, excluding chronic bronchitis, was associated with a PAR based on reported occupational exposure of 31% (95% CI 19-41%). Past occupational exposures significantly increased the likelihood of chronic obstructive pulmonary disease, independent of the effects of smoking. Given that one in five cases of chronic obstructive pulmonary disease may be attributable to occupational exposures, clinicians and health policy-makers should address this potential avenue of chronic obstructive pulmonary disease causation and its prevention.