tbuckley/cabot-search huggingface dataset:
Comparison of a guaiac based and an immunochemical faecal occult blood test in screening for colorectal cancer in a general average risk population
Authors: L Guittet, V Bouvier, N Mariotte, J P Vallee, D Arsene, S Boutreux, J Tichet, G Launoy
Journal: Gut (2006)

<b>Background:</b> The guaiac faecal occult blood test (G-FOBT) is recommended as a screening test for colorectal cancer but its low sensitivity has prevented its use throughout the world. <b>Methods:</b> We compared the performances of the reference G-FOBT (non-rehydrated Hemoccult II test) and the immunochemical faecal occult blood test (I-FOBT) using different positivity cut-off values in an average risk population sample of 10 673 patients who completed the two tests. Patients with at least one test positive were asked to undergo colonoscopy. <b>Results:</b> Using the usual cut-off point of 20 ng/ml haemoglobin, the gain in sensitivity associated with the use of I-FOBT (50% increase for cancer and 256% increase for high risk adenoma) was balanced by a decrease in specificity. The number of extra false positive results associated with the detection of one extra advanced neoplasia (cancer or high risk adenoma) was 2.17 (95% confidence interval 1.65–2.85). With a threshold of 50 ng/ml, I-FOBT detected more than twice as many advanced neoplasias as the G-FOBT (ratio of sensitivity = 2.33) without any loss in specificity (ratio of false positive rate = 0.99). With a threshold of 75 ng/ml, associated with a similar positivity rate to G-FOBT (2.4%), the use of I-FOBT allowed a gain in sensitivity of 90% and a decrease in the false positive rate of 33% for advanced neoplasia. <b>Conclusions:</b> Evidence in favour of the substitution of G-FOBT by I-FOBT is increasing, the gain being more important for high risk adenomas than for cancers. The automated reading technology allows choice of the positivity rate associated with an ideal balance between sensitivity and specificity.
Cough threshold in reflux oesophagitis: influence of acid and of laryngeal and oesophageal damage
Authors: L Benini
Journal: Gut (2000)

<h3>BACKGROUND</h3> Gastro-oesophageal reflux is often associated with cough. Patients with reflux show an enhanced tussive response to bronchial irritants, even in the absence of respiratory symptoms. <h3>AIM</h3> To investigate the effect of mucosal damage (either oesophageal or laryngeal) and of oesophageal acid flooding on cough threshold in reflux patients. <h3>PATIENTS</h3> We studied 21 patients with reflux oesophagitis and digestive symptoms. Respiratory diseases, smoking, and use of drugs influencing cough were considered exclusion criteria. <h3>METHODS</h3> Patients underwent pH monitoring, manometry, digestive endoscopy, laryngoscopy, and methacholine challenge. We evaluated the cough response to inhaled capsaicin (expressed as PD5, the dose producing five coughs) before therapy, after five days of omeprazole therapy, and when oesophageal and laryngeal damage had healed. <h3>RESULTS</h3> In all patients spirometry and methacholine challenge were normal. Thirteen patients had posterior laryngitis and eight complained of coughing. Twenty patients showed an enhanced cough response (basal PD5 0.92 (0.47) nM; mean (SEM)) which improved after five and 60 days (2.87 (0.82) and 5.88 (0.85) nM; p&lt;0.0001). The severity of oesophagitis did not influence PD5 variation. On the contrary, the response to treatment was significantly different in patients with and without laryngitis (p=0.038). In patients with no laryngitis, the cough threshold improved after five days with no further change thereafter. In patients with laryngitis, the cough threshold improved after five days and improved further after 60 days. Proximal and distal oesophageal acid exposure did not influence PD5. Heartburn disappeared during the first five days but the decrease in cough and throat clearing were slower. <h3>CONCLUSIONS</h3> Patients with reflux oesophagitis have a decreased cough threshold. This is related to both laryngeal inflammation and acid flooding of the oesophagus but not to the severity of oesophagitis. Omeprazole improves not only respiratory and gastro-oesophageal symptoms but also the cough threshold.
The Roles of Cellular and Organismal Aging in the Development of Late-Onset Maladies
Authors: Filipa Carvalhal Marques, Yuli Volovik, Ehud Cohen
Journal: Annual Review of Pathology Mechanisms of Disease (2014)

Numerous disorders, including neurodegenerative diseases and certain types of cancer, manifest late in life. This common feature raises the prospect that an aging-associated decline in the activity of cellular and organismal maintenance mechanisms enables the emergence of these maladies in late life stages. Accordingly, the alteration of aging bears the promise of harnessing the mechanisms that protect the young organism to prevent illness in the elderly. The identification of aging-regulatory pathways has enabled scrutiny of this hypothesis and revealed that the alteration of aging protects invertebrates and mammals from toxic protein aggregation linked to neurodegeneration and from cancer. Here we review the current knowledge on the regulation of aging at the cellular and organismal levels, delineate the mechanistic links between aging and late-onset disorders, describe efforts to develop compounds that protect from these maladies by selectively manipulating aging, and discuss future research directions and possible therapeutic implications of this approach.
Cytochrome p-450 gene expression in the functional units of the fetal liver
Authors: Jose Chianale, Caroline Dvorak, Donna L. Farmer, Linda Michaels, Jorge J. Gumucio
Journal: Hepatology (1988)

Hepatocytes of the right and left lobes of the fetal liver are surrounded by different microenvironments. The right and left lobes of the fetal liver are perfused by vascular systems carrying different concentrations of oxygen and constitute distinct functional units. The aim of this study was to assess the expression of the phenobarbital-inducible cytochrome P-450 b,e genes in hepatocytes of the right and left fetal liver lobes in mice. Northern-blot analysis using [ 32 P]cDNAs and quantitative dot-blot hybridization were performed to assess the size and levels of these mRNAs in the right and left fetal liver lobes. In fetal mice, the levels of cytochrome P-450, b,e mRNAs were higher in the left than in the right fetal liver lobe. During the last days of gestation and in the immediate postnatal period, the levels of liver cytochrome P-450 b,e mRNAs increased predominantly in the left liver lobe. In contrast, the levels of albumin and α-fetoprotein mRNAs (genes studied to assess the specificity of these findings) were similar in each of functional units of the fetal liver. Phenobarbital induction of cytochromes P-450 b,e mRNAs was not observed in either of the fetal liver lobes. Postnatally, phenobarbital induced these cytochromes similarly in the right and left liver lobes. Therefore, the microenvironment surrounding fetal hepatocytes seems to influence the expression of the cytochrome P-450 b,e genes. This lobar heterogeneity of expression disappears as the pattern of adult liver circulation is attained.
Blood pressure and incidence of twelve cardiovascular diseases: lifetime risks, healthy life-years lost, and age-specific associations in 1·25 million people
Authors: Eleni Rapsomaniki, Adam Timmis, Julie George, Mar Pujades-Rodriguez, Anoop D Shah, Spiros Denaxas, Ian R White, Mark J Caulfield, John E Deanfield, Liam Smeeth, Bryan Williams, Aroon Hingorani, Harry Hemingway
Journal: The Lancet (2014)

The associations of blood pressure with the different manifestations of incident cardiovascular disease in a contemporary population have not been compared. In this study, we aimed to analyse the associations of blood pressure with 12 different presentations of cardiovascular disease.
Assessment of symptomatic women for early diagnosis of ovarian cancer: results from the prospective DOvE pilot project
Authors: Lucy Gilbert, Olga Basso, John Sampalis, Igor Karp, Claudia Martins, Jing Feng, Sabrina Piedimonte, Louise Quintal, Agnihotram V Ramanakumar, Janet Takefman, Maria S Grigorie, Giovanni Artho, Srinivasan Krishnamurthy
Journal: The Lancet Oncology (2012)
Factor XIIa and triacylglycerol rich lipoproteins: responses to exercise intervention
Authors: K Woolf-May, W Jones, E M Kearney, R C R Davison, S Bird
Journal: British Journal of Sports Medicine (2000)

Objectives —( a ) To determine if factor XIIa (FXIIa) would be sensitive to change from exercise intervention in a group of previously sedentary/low active middle aged men and women; ( b ) to investigate further the previously reported relation between FXIIa and triacylglycerol (TAG) rich lipoproteins. Methods —Thirty seven men (mean (SD) age 57 (7) years) and 60 women (mean age 54 (7) years) completed the study. Before the intervention, these subjects were randomly allocated to a group of walkers (n = 81) or controls (n = 16). Before and after an 18 week walking intervention, fasted blood samples were collected and analysed for FXIIa, TAG, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and apolipoprotein (apo) B. Results —Kruskal-Wallis analysis of data obtained before the intervention showed no significant differences (p&gt;0.4) between the walking and control groups for age, height, body mass, gender, FXIIa, TAG, TC, HDL-C, or apo B, although the women did show significantly lower levels of TAG (p&lt;0.04) and higher HDL-C (p&lt;0.0001) than the men. General linear model analysis of data obtained after the intervention, using the baseline value as a covariate, showed significant reductions (p&lt;0.0001) in FXIIa for the walkers compared with the controls. Pearson product-moment correlations also showed significant relations between the concentrations of FXIIa and TAG, TC, LDL-C, and apo B. Conclusions —The findings of this study suggest that FXIIa is sensitive to change from exercise intervention and support previous research showing an association between the concentrations of FXIIa and TAG rich lipoproteins.
Clonal Evolution, Genomic Drivers, and Effects of Therapy in Chronic Lymphocytic Leukemia
Authors: Peter Ouillette, Kamlai Saiya-Cork, Erlene Seymour, Cheng Li, Kerby Shedden, Sami N. Malek
Journal: Clinical Cancer Research (2013)

The identification of gene mutations and structural genomic aberrations that are critically involved in chronic lymphocytic leukemia (CLL) pathogenesis is still evolving. One may postulate that genomic driver lesions with effects on CLL cell proliferation, apoptosis thresholds, or chemotherapy resistance should increase in frequency over time when measured sequentially in a large CLL cohort.We sequentially sampled a large well-characterized CLL cohort at a mean of 4 years between samplings and measured acquired copy number aberrations (aCNA) and LOH using single-nucleotide polymorphism (SNP) 6.0 array profiling and the mutational state of TP53, NOTCH1, and SF3B1 using Sanger sequencing. The paired analysis included 156 patients, of whom 114 remained untreated and 42 received intercurrent therapies, predominantly potent chemoimmunotherapy, during the sampling interval.We identify a strong effect of intercurrent therapies on the frequency of acquisition of aCNAs in CLL. Importantly, the spectrum of acquired genomic changes was largely similar in patients who did or did not receive intercurrent therapies; therefore, various genomic changes that become part of the dominant clones are often already present in CLL cell populations before therapy. Furthermore, we provide evidence that therapy of CLL with preexisting TP53 mutations results in outgrowth of genomically very complex clones, which dominate at relapse.Using complementary technologies directed at the detection of genomic events that are present in substantial proportions of the clinically relevant CLL disease bulk, we capture aspects of genomic evolution in CLL over time, including increases in the frequency of genomic complexity, specific recurrent aCNAs, and TP53 mutations.
Weak Yet Distinct Mutagenicity of Acrylamide in Mammalian Cells
Authors: A. Besaratinia, G. P. Pfeifer
Journal: JNCI Journal of the National Cancer Institute (2003)

Despite concern raised with the announcement that common heating processes such as frying introduce acrylamide, a known rodent carcinogen, into food, the mutagenicity of acrylamide in mammalian DNA is controversial.Big Blue mouse embryonic fibroblasts, which carry a lambda phage cII transgene, were treated with acrylamide. Formation of DNA adducts was determined by terminal transferase-dependent polymerase chain reaction. Mutational events were detected with a lambda phage-based mutagenesis assay and expressed as the frequency of the number of mutant cII plaques per total number of plaques screened. Mutations were confirmed by DNA sequence analysis. All statistical tests were two-sided.In vitro treatment of the cells with acrylamide at millimolar concentrations induced DNA adducts along the cII gene. Treatment with acrylamide at micromolar concentrations increased the frequency of mutations in the cII gene up to twofold relative to control treatment (13.8 x 10(-5), 95% confidence interval [CI] = 12.3 to 15.3 x 10(-5) versus 6.9 x 10(-5), 95% CI = 6.5 to 7.3 x 10(-5), df = 2, 21; P<.001; ANOVA). The specificity of acrylamide in inducing cII gene mutations was shown by a statistically significantly different mutational spectrum from that in control-treated cells, with an excess of G --> C transversions and A --> G transitions (P =.024; Adams and Skopek test). Although some of the frequently mutated sites in the cII gene co-localized with sites of preferential DNA adduct formation, there was no direct relationship.Acrylamide had distinct mutagenicity in transgenic mouse embryonic fibroblast cells, which might potentially be ascribed to its DNA adduct-inducing property. Whether acrylamide has the same effects on human cells is yet to be determined.
STUDIES OF METABOLISM IN THE DOG BEFORE AND AFTER REMOVAL OF THE SPLEEN
Authors: Samuel Goldschmidt, Richard M. Pearce
Journal: The Journal of Experimental Medicine (1915)

Four dogs have been subjected to metabolism studies before splenectomy and at intervals of three days to three months after splenectomy. In three of the four animals the removal of the spleen was not followed by any disturbances of nitrogen metabolism, fat utilization, or iron elimination. Two of these animals showed no anemia, and the third only a slight reduction in hemoglobin and number of red cells. A fourth animal, studied ten days and three months after splenectomy, developed eventually a definitely progressive anemia of moderate severity. This animal showed a slight loss of weight, a slight disturbance of nitrogen balance, and of creatine-creatinine partition, with a marked increase in the elimination of iron. We conclude therefore that the spleen has no important influence on metabolism, and that the disturbances occurring in one of our dogs were due to the coexisting anemia and not to the absence of the spleen.
International Differences in Dialysis Mortality Reflect Background General Population Atherosclerotic Cardiovascular Mortality
Authors: Maki Yoshino, Martin K Kuhlmann, Peter Kotanko, Roger N Greenwood, Ronald L Pisoni, Friedrich K Port, Kitty J Jager, Peter Homel, Hans Augustijn, Frank T de Charro, Frederic Collart, Ekrem Erek, Patrik Finne, Guillermo Garcia-Garcia, Carola Grönhagen-Riska, George A Ioannidis, Frank Ivis, Torbjorn Leivestad, Hans Løkkegaard, Frantisek Lopot, Dong-Chan Jin, Reinhard Kramar, Toshiyuki Nakao, Mooppil Nandakumar, Sylvia Ramirez, Frank M van der Sande, Staffan Schön, Keith Simpson, Rowan G Walker, Wojciech Zaluska, Nathan W Levin
Journal: Journal of the American Society of Nephrology (2006)

Existing national, racial, and ethnic differences in dialysis patient mortality rates largely are unexplained. This study aimed to test the hypothesis that mortality rates related to atherosclerotic cardiovascular disease (ASCVD) in dialysis populations (DP) and in the background general populations (GP) are correlated. In a cross-sectional, multinational study, all-cause and ASCVD mortality rates were compared between GP and DP using the most recent data from the World Health Organization mortality database (67 countries; 1,571,852,000 population) and from national renal registries (26 countries; 623,900 population). Across GP of 67 countries (14,082,146 deaths), all-cause mortality rates (median 8.88 per 1000 population; range 1.93 to 15.40) were strongly related to ASCVD mortality rates (median 3.21; range 0.53 to 8.69), with Eastern European countries clustering in the upper and Southeast and East Asian countries in the lower rate ranges. Across DP (103,432 deaths), mortality rates from all causes (median 166.20; range 54.47 to 268.80) and from ASCVD (median 63.39 per 1000 population; range 21.52 to 162.40) were higher and strongly correlated. ASCVD mortality rates in DP and in the GP were significantly correlated; the relationship became even stronger after adjustment for age (R(2) = 0.56, P < 0.0001). A substantial portion of the variability in mortality rates that were observed across DP worldwide is attributable to the variability in background ASCVD mortality rates in the respective GP. Genetic and environmental factors may underlie these differences.
Gene Signatures for the Prediction of Response to Bacillus Calmette-Guérin Immunotherapy in Primary pT1 Bladder Cancers
Authors: Yong-June Kim, Yun-Sok Ha, Seon-Kyu Kim, Hyung Yoon Yoon, Min Su Lym, Min-Ju Kim, Sung-Kwon Moon, Yung Hyun Choi, Wun-Jae Kim
Journal: Clinical Cancer Research (2010)

Intravesical Bacillus Calmette-Guérin (BCG) immunotherapy is effective in the prevention of recurrence and progression in many cases of nonmuscle invasive bladder cancer, but many patients fail to respond. The aim of this study was to identify gene sets of markers that could predict the response to BCG immunotherapy in primary pT1 bladder cancer using microarray gene expression profiling.We used 80 patients with primary pT1 bladder cancer treated with BCG immunotherapy as training (48) and test (32) sets. Microarray gene expression profiling was done in the training set to identify genes differentially expressed between responder and nonresponder to BCG immunotherapy according to the events (recurrence or progression). Using a real-time reverse-transcriptase PCR, our findings were validated in the test set.In the training set, 424 and 287 genes were significantly associated with recurrence- and progression-free survival, respectively. Functional annotation of these genes included cell-mediated immune response, inflammatory response, cellular growth, and proliferation. From these predictive gene signatures, 24 genes (12 in recurrence and 12 in progression) with the highest score of expression ratio were extracted for validation in the test set. In multivariate regression analyses, predictive gene signatures were the only independent predictors of recurrence (hazard ratio, 3.38; P = 0.048) or progression (hazard ratio, 10.49; P = 0.048) in the test set.Predictive gene signatures have diagnostic value for determining the response to intravesical BCG immunotherapy in primary pT1 bladder cancer.
Chemotherapeutic Resistance: Surviving Stressful Situations
Authors: Luke A. Gilbert, Michael T. Hemann
Journal: Cancer Research (2011)

Chemotherapeutic regimens involve the systemic administration of genotoxic compounds that induce cancer cell death via well-established DNA damage response signaling networks. Less understood is how the treatment of other cell types within the tumor microenvironment affects the therapeutic response. Here we discuss recent work that shows that tumor-adjacent cells can respond to genotoxic stress by activating a paracrine secretory program. Although this secretory response serves to protect progenitor cells and promote tissue regeneration in conditions of cellular stress, it can also be coopted by tumor cells to survive frontline chemotherapy. Thus, local prosurvival signaling may present a fundamental barrier to tumor clearance by genotoxic agents, suggesting that effective treatments need to target both cancer cells and the tumor microenvironment.
Daily aciclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial
Authors: Jairam R Lingappa, Jared M Baeten, Anna Wald, James P Hughes, Katherine K Thomas, Andrew Mujugira, Nelly Mugo, Elizabeth A Bukusi, Craig R Cohen, Elly Katabira, Allan Ronald, James Kiarie, Carey Farquhar, Grace John Stewart, Joseph Makhema, Myron Essex, Edwin Were, Kenneth H Fife, Guy de Bruyn, Glenda E Gray, James A McIntyre, Rachel Manongi, Saidi Kapiga, David Coetzee, Susan Allen, Mubiana Inambao, Kayitesi Kayitenkore, Etienne Karita, William Kanweka, Sinead Delany, Helen Rees, Bellington Vwalika, Amalia S Magaret, Richard S Wang, Lara Kidoguchi, Linda Barnes, Renee Ridzon, Lawrence Corey, Connie Celum
Journal: The Lancet (2010)
Genome-wide profiling of target genes for the systemic lupus erythematosus-associated transcription factors IRF5 and STAT4
Authors: Chuan Wang, Johanna K Sandling, Niklas Hagberg, Olof Berggren, Snaevar Sigurdsson, Olof Karlberg, Lars Rönnblom, Maija-Leena Eloranta, Ann-Christine Syvänen
Journal: Annals of the Rheumatic Diseases (2012)

<b>Background:</b> Excess cardiovascular mortality complicates systemic rheumatic disease, suggesting an accelerated atheromatous process, which it has been proposed relates to the vascular inflammation common in such diseases. Impaired endothelium dependent vasodilatation is an early marker of atheromatous disease. It has previously been shown that such endothelial cell dysfunction (ECD) occurring in the brachial artery can complicate primary systemic necrotising vasculitis (SNV). <b>Objective:</b> To determine if ECD occurs in a wider spectrum of primary SNV, if it is restricted to the major arteries, and whether vasculitis subgroup, ANCA status, or renal involvement influenced the endothelial responses. <b>Methods:</b> Fifty four patients attending the Birmingham vasculitis clinic, including patients with a range of ANCA and non-ANCA associated primary vasculitides, and a group of age matched controls were recruited. The length of patient follow up and disease activity was variable. Disease activity, damage scores, and cardiovascular risk factors were recorded before assessment of flow mediated brachial artery vasodilatation by high resolution ultrasound. Dermal microvascular responses to acetylcholine were also measured in 32 patients and 21 controls by laser Doppler flowmetry. <b>Results:</b> ECD was demonstrated in all primary SNV subgroups of patients with ANCA associated vasculitis and in polyarteritis nodosa, compared with controls. Significant impairment occurred in both vascular beds, regardless of vessel size targeted in the inflammatory vasculitis, ANCA association and titre, or renal involvement. <b>Conclusions:</b> Diffuse endothelial dysfunction, a predictor of atherosclerotic disease, is found extensively in primary systemic vasculitis. Involvement of different vascular beds is independent of target vessel size or ANCA association, and is unrelated to local disease expression. It is suggested that this results from a systemic response that may be a consequence of primary vasculitis, but is distinct from the local inflammatory vasculitic process.