tbuckley/cabot-search huggingface dataset:
Expression of interleukin 8 (IL-8) and substance P in human chronic pancreatitis
Authors: P Di Sebastiano
Journal: Gut (2000)

Changes in substance P content and a relationship between the degree of perineural inflammation and pain has been demonstrated in chronic pancreatitis. Whether a relationship exists between neural alteration and pancreatic inflammation (neurogenic inflammation) is not known.In the present study we evaluated gene expression of preprotachykinin A (PPT-A), the gene encoding substance P, and interleukin 8, a proinflammatory and hyperalgesic mediator whose release is co-regulated by substance P.Pancreatic tissue specimens obtained from 21 patients (16 male, five female) with chronic pancreatitis and 18 healthy organ donors (nine male, nine female) were analysed.Gene expression of PPT-A and interleukin 8 was studied by northern blot analysis. Respective proteins were localised using immunohistochemistry.Northern blot analysis showed that PTT-A mRNA expression levels were present at comparable levels in normal and chronic pancreatitis tissue samples. In contrast, interleukin 8 mRNA was expressed at very low levels in normal controls but was increased 41-fold (p<0. 001) in chronic pancreatitis tissue samples. Using immunohistochemistry, interleukin 8 protein was localised mainly in immune cells often found around enlarged pancreatic nerves. In addition, in chronic pancreatitis, intense interleukin 8 immunostaining was present in metaplastic ductal cells of the atrophic pancreatic parenchyma. In chronic pancreatitis samples there was a positive relationship between interleukin 8 mRNA levels and the presence of ductal metaplasia (r=0.795; p<0.001) and the inflammation score (r=0.713; p<0.001).Our data indicate that in chronic pancreatitis, the increase in substance P in enlarged pancreatic nerves is not caused by enhanced intrapancreatic PTT-A mRNA expression, suggesting that the location of substance P synthesis is outside of the pancreas. In addition, localisation of interleukin 8 positive immune cells around pancreatic nerves further supports the existence of neuroimmune interactions as a pathophysiological mechanism in chronic pancreatitis.
Early short-term versus prolonged low-dose methylprednisolone therapy in acute lung injury
Authors: P. L. Silva, C. S. N. B. Garcia, P. A. Maronas, V. R. Cagido, E. M. Negri, N. R. Damaceno-Rodrigues, G. M. Ventura, P. T. Bozza, W. A. Zin, V. L. Capelozzi, P. Pelosi, P. R. M. Rocco
Journal: European Respiratory Journal (2008)

The present study compared the effects of early short-term with prolonged low-dose corticosteroid therapy in acute lung injury (ALI). In total, 120 BALB/c mice were randomly divided into five groups. In the control group, saline was intratracheally ( i.t. ) instilled. In the ALI group, mice received Escherichia coli lipopolysaccharide (10 μg i.t. ). ALI animals were further randomised into four subgroups to receive saline (0.1 mL i.v. ) or methylprednisolone (2 mg·kg −1 i.v. ) at 6 h, 24 h or daily (for 7 days, beginning at day 1). At 1, 3 and 8 weeks, in vivo and in vitro lung mechanics and histology (light and electron microscopy), collagen and elastic fibre content, cytokines in bronchoalveolar lavage fluid and the expression of matrix metalloproteinase (MMP)-9 and -2 were measured. In vivo (static elastance and viscoelastic pressure) and in vitro (tissue elastance and resistance) lung mechanics, alveolar collapse, cell infiltration, collagen and elastic fibre content and the expression of MMP-9 and MMP-2 were increased in ALI at 1 week. Methylprednisolone led to a complete resolution of lung mechanics, avoided fibroelastogenesis and the increase in the expression of MMP-9 and MMP-2 independent of steroid treatment design. Thus, early short-term, low-dose methylprednisolone is as effective as prolonged therapy in acute lung injury.
Epidermal Growth Factor Receptor, c-MET, β-Catenin, and p53 Expression as Prognostic Indicators in Stage II Colon Cancer
Authors: Murray B. Resnick, Justin Routhier, Tamako Konkin, Edmond Sabo, Victor E. Pricolo
Journal: Clinical Cancer Research (2004)

Abstract Purpose: Through the use of molecular markers, it may be possible to identify aggressive tumor phenotypes and tailor therapies to treat them. This approach would be particularly useful for stage II colon cancer. The purpose of this study was to define the prognostic value of epidermal growth factor receptor (EGFR), c-MET, β-catenin, and p53 protein expression in TNM stage II colon cancer using tissue microarray technology. Experimental Design: In this study, we retrospectively analyzed, resected, and otherwise untreated paraffin-embedded specimens from 134 consecutive patients with Tumor-Node-Metastasis stage II colonic carcinomas for EGFR, c-MET, β-catenin, and p53 protein expression by immunohistochemistry. Results: Thirty-five percent, 77, and 65% of tumors exhibited strong (+2 and +3 immunopositivity) expression of EGFR, c-MET, and β-catenin, respectively. Fifty-four percent exhibited nuclear staining for p53 in &amp;gt;10% of the tumor cells. Univariate analysis revealed that increased nuclear p53 expression (P = 0.001), strong membranous EGFR expression (P = 0.04), and lymphovascular invasion (P = 0.01) were significantly related to disease recurrence and that p53 (P = 0.02) and EGFR (P = 0.05) expression were associated with decreased survival. Increased nuclear p53 expression also correlated with the presence of distal metastasis (P = 0.027). No significant association was seen between c-MET expression and prognosis, whereas a strong trend was detected between loss of β-catenin (P = 0.065) expression and poor outcome. Multivariate analysis indicated that p53 (P = 0.04), EGFR (P = 0.05), and lymphovascular invasion (P = 0.03) were independent predictors of recurrence and that p53 (P = 0.02) and EGFR (P = 0.01) expression were both associated with poor survival. Conclusions: This retrospective tumor microarray study, restricted to Tumor-Node-Metastasis stage II colon cancer patients who did not undergo adjuvant therapy, supports the use of EGFR and p53 as biological markers, which may assist in predicting disease recurrence and survival.
Signalling in osteoclasts and the role of Fos/AP1 proteins
Authors: E F Wagner
Journal: Annals of the Rheumatic Diseases (2003)

he analysis of genetically modified mice and cells has provided important new insights into the biological functions of the dimeric transcription factor complex AP1.The key components of AP1, the Fos and Jun proteins, have essential roles in bone development, because these proteins influence the activity of all bone cells, including chondrocytes, osteoblasts, and osteoclasts.New AP1 functions and their downstream effectors were recently discovered using conditional mutagenesis in the mouse as well as by genome-wide analysis of AP1 inducible genes, in particular in the osteoclast lineage.The signal transduction pathways operating in osteoclastogenesis have been extensively studied and how extracellular stimuli lead to the activation of key transcriptional programmes is beginning to be understood.The events downstream of macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) signalling are well described.Positive and negative regulatory loops are in place, which involve the activation of NF-κB and Jun N-terminal kinase (JNK), eventually leading to the expression of AP1/Fos, an essential regulator of osteoclast differentiation.AP1 consists of a large variety of dimers composed of members of the Fos proteins-Fos, FosB, Fra1, and Fra2; the three Jun proteins-Jun, JunB, and JunD; and ATF proteins (for review see Karsenty and Wagner 1 and Jochum et al 2 ).AP1 acts like a biosensor in cells and is often considered as a stress responsive transcription factor complex.Being at the receiving end of several signal transduction cascades, AP1 activity converts extracellular signals from, for example, growth factor receptors, through mitogen activated protein kinase (MAPK) into changes in gene expression via expression of AP1 responsive target genes.The activity of AP1 is regulated at different levels-transcriptional and post-transcriptional; it is also modulated by interactions with other transcriptional regulators.AP1 activity is implicated in a wide range of biological processes, including cell proliferation, differentiation, apoptosis, and oncogenesis. 2 3Here we will give a brief summary of the current knowledge and understanding of AP1 functions in bone development and will focus on the role of AP1 in signal transduction in osteoclasts.These data were largely obtained from an analysis of genetically modified mice and cells, in which specific AP1 genes were ectopically expressed, constitutively or conditionally inactivated, mutated, or replaced by each other.. . . . . . . . . . .
Reconstructing (Super)Trees from Data Sets with Missing Distances: Not All Is Lost
Authors: George Kettleborough, Jo Dicks, Ian N. Roberts, Katharina T. Huber
Journal: Molecular Biology and Evolution (2015)

The wealth of phylogenetic information accumulated over many decades of biological research, coupled with recent technological advances in molecular sequence generation, presents significant opportunities for researchers to investigate relationships across and within the kingdoms of life. However, to make best use of this data wealth, several problems must first be overcome. One key problem is finding effective strategies to deal with missing data. Here, we introduce Lasso, a novel heuristic approach for reconstructing rooted phylogenetic trees from distance matrices with missing values, for data sets where a molecular clock may be assumed. Contrary to other phylogenetic methods on partial data sets, Lasso possesses desirable properties such as its reconstructed trees being both unique and edge-weighted. These properties are achieved by Lasso restricting its leaf set to a large subset of all possible taxa, which in many practical situations is the entire taxa set. Furthermore, the Lasso approach is distance-based, rendering it very fast to run and suitable for data sets of all sizes, including large data sets such as those generated by modern Next Generation Sequencing technologies. To better understand the performance of Lasso, we assessed it by means of artificial and real biological data sets, showing its effectiveness in the presence of missing data. Furthermore, by formulating the supermatrix problem as a particular case of the missing data problem, we assessed Lasso's ability to reconstruct supertrees. We demonstrate that, although not specifically designed for such a purpose, Lasso performs better than or comparably with five leading supertree algorithms on a challenging biological data set. Finally, we make freely available a software implementation of Lasso so that researchers may, for the first time, perform both rooted tree and supertree reconstruction with branch lengths on their own partial data sets.
E2F-Dependent Repression of Topoisomerase II Regulates Heterochromatin Formation and Apoptosis in Cells with Melanoma-Prone Mutation
Authors: Wan Jiao, Huei-Min Lin, Jamie Timmons, Akhilesh K. Nagaich, Shu-Wing Ng, Tom Misteli, Sushil G. Rane
Journal: Cancer Research (2005)

Abstract RB pathway mutations, especially at the CDK4 and INK4A loci, are hallmarks of melanomagenesis. It is presently unclear what advantages these alterations confer during melanoma progression and how they influence melanoma therapy. Topoisomerase II inhibitors are widely used to treat human malignancies, including melanoma, although their variable success is attributable to a poor understanding of their mechanism of action. Using mouse and human cells harboring the melanoma-prone p16Ink4a-insensitive CDK4R24C mutation, we show here that topoisomerase II proteins are direct targets of E2F-mediated repression. Drug-treated cells fail to load repressor E2Fs on topoisomerase II promoters leading to elevated topoisomerase II levels and an enhanced sensitivity of cells to apoptosis. This is associated with the increased formation of heterochromatin domains enriched in structural heterochromatin proteins, methylated histones H3/H4, and topoisomerase II. We refer to these preapoptotic heterochromatin domains as apoptosis-associated heterochromatic foci. We suggest that cellular apoptosis is preceded by an intermediary chromatin remodeling state that involves alterations of DNA topology by topoisomerase II enzymes and gene silencing via formation of heterochromatin. These observations provide novel insight into the mechanism of drug action that influence treatment outcome: drug sensitivity or drug resistance.
Conversion of blood androgens to estrogens in normal adult men and women
Authors: Christopher Longcope, Tatsuo Kato, Richard Horton
Journal: Journal of Clinical Investigation (1969)

Continuous infusions of Delta(4)-androstenedione-7-(3)H and testosterone-7-(3)H have been used to demonstrate that these androgens are converted to estrone and 17beta-estradiol, and contribute to the circulating blood levels of these estrogens in normal males and females. The conversion ratio (ratio of concentrations of radioactivity of free product steroid [chi(-PRO)] and free precursor steroid [chi(-PRE)], both corrected for recoveries, after an infusion of radioactive precursor steroid) for androstenedione (precursor) to estrone (product) is 0.013 in males and 0.007 in females, and the conversion ratio for testosterone (precursor) to estradiol (product) is 0.0018 in males and 0.005 in females. The transfer constant, [rho](BB) (AE1), for androstenedione conversion to estrone ([rho](BB) (AE1) = per cent of infused androstenedione, precursor, converted to estrone, product, when infusion and measurement are both in blood) is 1.35% in males and 0.74% in females, and the transfer constant, [rho](BB) (TE2), for testosterone conversion to estradiol is 0.39% in males and 0.15% in females. Whether measured as conversion ratio or transfer constant, the peripheral aromatization of androstenedione takes place to a greater degree than that of testosterone, and, for the respective androgens, both the conversion ratio and [rho](BB) value are greater in males than females. For the androgen interconversions, [rho](BB) (AT) is 4.5% in males and 2.2% in females; [rho](BB) (TA) is 8.2% in males and 12.0% in females. Studies on the distribution coefficients (effective concentration in red cells/plasma) for precursor radioactivity were also made. In both males and females the distribution coefficient for androstenedione is 0.16-0.17 while that of testosterone is 0.01-0.03.
Teaser: Individualized benchmarking and optimization of read mapping results for NGS data
Authors: Moritz Smolka, Philipp Rescheneder, Michael C. Schatz, Arndt von Haeseler, Fritz J. Sedlazeck
Journal: Genome biology (2015)

Mapping reads to a genome remains challenging, especially for non-model organisms with lower quality assemblies, or for organisms with higher mutation rates. While most research has focused on speeding up the mapping process, little attention has been paid to optimize the choice of mapper and parameters for a user's dataset. Here, we present Teaser, a software that assists in these choices through rapid automated benchmarking of different mappers and parameter settings for individualized data. Within minutes, Teaser completes a quantitative evaluation of an ensemble of mapping algorithms and parameters. We use Teaser to demonstrate how Bowtie2 can be optimized for different data.
Response to Comment on Liu et al. Latent Autoimmune Diabetes in Adults With Low-Titer GAD Antibodies: Similar Disease Progression With Type 2 Diabetes: A Nationwide, Multicenter Prospective Study (LADA China Study 3). Diabetes Care 2015;38:16–21
Authors: Xia Li, Lingjiao Liu, Yufei Xiang, Gan Huang, R. David Leslie, Zhiguang Zhou
Journal: Diabetes Care (2015)

We thank Shah and Yu (1) for their comments on our study (2) and for the opportunity to discuss some key points on the GAD antibody (GADA) pattern and its relation with progression of type 1 diabetes, especially for latent autoimmune diabetes in adults (LADA). They suggest that low-titer GADA subjects in our study might have low-affinity GADA representing biologically “false positivity” and GADA affinity could be analyzed with an electrochemiluminescence (ECL)-based …
Differences in Lung Cancer Risk Between Men and Women: Examination of the Evidence
Authors: E. A. Zang, E. L. Wynder
Journal: JNCI Journal of the National Cancer Institute (1996)

Lung cancer incidence is gradually leveling off in U.S. men but is continuing to rise in U.S. women. This increase in U.S. women exceeds that expected from a slower decline of smoking among women. Recent epidemiologic and biochemical studies suggest gender differences in susceptibility to tobacco carcinogens. We conducted an up-to-date, more in-depth evaluation of our earlier observation of a potential gender difference in relative risk (RR) of lung cancer due to smoking. We added information from several additional case and control subjects and included more precise histologic classification of the cancer type, accurate quantitation of smoke exposure, and adjustments for body size. The present investigation was a part of an ongoing hospital-based, case—control study by the American Health Foundation. It included data from 1889 case subjects (1108 males and 781 females) with lung cancer of squamous/epidermoid, small-cell/oat cell, large-cell, and adenocarcinoma types and 2070 control subjects (1122 males and 948 females) with diseases unrelated to smoking. The case and control subjects were admitted to participating hospitals from 1981 to 1994 and were pair-matched by age, sex, hospital, and the time of hospital admission. Ex-smokers and non-Caucasians were excluded from analyses to avoid confounding. The RRs and 95% confidence intervals were estimated from adjusted odds ratios (ORs) by use of unconditional multiple logistic regression analysis, and statistical significance was determined by two-sided tests. The ORs for major histologic types were estimated at increasing levels of exposure to cigarette smoke. Our results indicated that women were more likely to be never-smokers than men, particularly those with the squamous/epidermoid-type cancer (8.3% for women versus 2.9% for men 55 years old or older). Men started smoking earlier, reported inhaling more deeply, and smoked more cigarettes per day than women. In contrast, dose—response ORs over cumulative exposure to cigarette smoking were 1.2-fold to 1.7-fold higher in women than in men for the three major histologic types; these differences were more pronounced for small-cell/oat cell carcinomas and adenocarcinomas than for squamous/epidermoid carcinomas. Adjustments for weight, height, or body mass index did not alter the ORs. These results confirm our earlier finding that the ORs for major lung cancer types are consistently higher for women than for men at every level of exposure to cigarette smoke. Furthermore, this gender difference cannot be explained by differences in base-line exposure, smoking history, or body size, but it is likely due to the higher susceptibility to tobacco carcinogens in women. [J Natl Cancer Inst 1996;88:183–92]
Hepatic expansion of a virus-specific regulatory CD8+ T cell population in chronic hepatitis C virus infection
Authors: Daniele Accapezzato, Vittorio Francavilla, Marino Paroli, Marco Casciaro, Lucia Valeria Chircu, Agostino Cividini, Sergio Abrignani, Mario U. Mondelli, Vincenzo Barnaba
Journal: Journal of Clinical Investigation (2004)

Regulatory T (TR) cells consist of phenotypically and functionally distinct CD4+ and CD8+ T cell subsets engaged both in maintaining self-tolerance and in preventing anti–non-self effector responses (microbial, tumor, transplant, and so on) that may be harmful to the host. Here we propose that the proinflammatory function of virus-specific memory effector CCR7–CD8+ T cells, which are massively recruited in the liver, are inefficient (in terms of IFN-γ production) in patients with chronic hepatitis C virus (HCV) infection because of the concomitant presence of virus-specific CCR7–CD8+ TR cells producing considerable amounts of IL-10. These CD8+ TR cells are antigen specific, as they can be stimulated by HCV epitopes and suppress T cell responses that are in turn restored by the addition of neutralizing anti–IL-10. This study provides for the first time to our knowledge direct evidence of the existence of virus-specific CD8+ TR cells that infiltrate the livers of patients with chronic HCV infection, identifies IL-10 as a soluble inhibitory factor mediating suppression, and suggests that these cells play a pivotal role in controlling hepatic effector CD8+ T cell responses.
An Unusual Localized Progressive Fibrotic Cavity Mimicking Lung Malignancy in Idiopathic Pulmonary Fibrosis
Authors: Chi Ryang Chung, Seoung Ju Park, Kyung Hoon Min, So Ri Kim, Min Hee Lee, Hyo Jin Han, Kyoung Hwa Choi, Gong Yong Jin, Myung Ja Chung, Yong Chul Lee
Journal: American Journal of Respiratory and Critical Care Medicine (2011)
Dimensions of Respiratory Symptoms in Preschool Children
Authors: Jaclyn A. Smith, Richard Drake, Angela Simpson, Ashley Woodcock, Andrew Pickles, Adnan Custovic
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

A focus on distinctive collections of symptoms may be more informative of the probability of respiratory disease than individual and possibly transient phenotypes. However, such collections or components of overall symptomatology need to be valid, and their relationship established with the known risk factors and physiologic measures.To analyze detailed parentally reported respiratory symptoms by principal components analysis and derive symptom components; to examine the relationship of such components with measures of lung physiology and atopy.An unselected, population-based birth cohort (n = 946).Interviewer-administered questionnaires, lung function (specific airway resistance [sRaw]), airway reactivity (dry air challenge), and atopic status were obtained at ages 3 and 5 years; principal components analysis and multivariate analysis of variance were used to analyze the data. The four-component solution (wheeze, cough, colds, chronic symptoms) explained 53.2% of the variance in symptoms at age 3, and the five-component solution (wheeze, wheeze with irritants, wheeze with allergens, cough, chest congestion) explained 49.8% of variance at age 5. The multivariate analysis revealed novel relationships between symptoms, risk factors for asthma, and measures of lung function. At age 3, sRaw and the interaction between maternal asthma and child's atopy were not only related to wheeze but also independently to the cough component. At age 5, overall wheeze and allergic wheeze were related to lung function and airway reactivity; child's atopy was only related to symptoms when considered as a continuous trait.Our analysis supports the need to move beyond the presence or absence of individual symptoms. Syndromes of coexisting symptoms more likely reflect underlying pathophysiologic processes.
Treatment of Hepatic Encephalopathy by Surgical Exclusion of the Colon
Authors: H. Alan Hume
Journal: JAMA (1966)

NEUROPSYCHIATRIC disorders associated with liver disease have been under intensive clinical and laboratory investigation for the past decade. The precise causes and metabolic aberrations responsible for these syndromes are not completely understood. Exclusion or removal of the colon has a favorable effect on this disorder in properly selected patients. This case report confirms the work of McDermott and others<sup>1-3</sup>and emphasizes the reversibility of this progressive and ultimately fatal disorder. <h3>Report of a Case</h3> The medical history of the patient, age 65, is outlined in Table 1. Following portacaval shunting the patient did rather well and was discharged on a 70-gm protein diet and a regimen of neomycin sulfate, 0.25 gm orally four times daily. He was readmitted two months postoperatively in mild coma with a history of omitting neomycin for five days. Clinically he showed slurring of speech, a staggering gait, loss of ability to feed himself or