tbuckley/cabot-search huggingface dataset:
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Authors: Ju Dong Yang, Cynthia D. Guy, Ayako Suzuki
Journal: Hepatology (2014)

We enjoyed reading the letter from Marcos et al. regarding our recent publication on the association of gender and menopause with the severity of liver fibrosis in patients with nonalcoholic steatohepatitis (NASH).1 In their study, the authors quantified a volume of fibrous tissue in the liver samples from healthy male (n = 20) and female (n = 20) rats using a stereological system. Interestingly, male rats were found to have 34% more fibrous tissues than female rats. This difference was independent of liver volume or weight. The authors state that this difference was mainly attributed to the difference in perisinusoidal fibrous tissue deposition. The authors speculated that men's liver, even before development of NASH, may contain a greater quantity of extracellular matrix, which may contribute to a higher stage of liver fibrosis in men compared to women. In normal human liver, connective tissues exist around vessels and bile ducts and mainly in the portal tracts. In the lobule, sinusoid spaces are lined by specialized endothelial cells which lack a basement membrane. The space of Disse separates the sinusoids from the hepatic plates which are supported by a delicate reticulin framework. Fibrous tissue per se is not usually observed in perisinusoidal spaces in the normal human liver. With our current knowledge, we are uncertain how we can translate the author's findings in rats into implications for human liver disease. In any event, delineating sex-biased biology and pathobiology in liver diseases is a key to building a knowledge base for future personalized medicine. Further investigations in gender-biased biology and pathobiology are encouraged. Ju Dong Yang, M.D., M.Sc.1 Cynthia D. Guy, M.D.2 Ayako Suzuki, M.D., Ph.D., M.Sc.3,4 1Division of Gastroenterology and Hepatology Mayo Clinic College of Medicine Rochester, MN 2Department of Pathology Duke University Medical Center Durham, NC 3Division of Gastroenterology Central Arkansas Veterans Healthcare System Little Rock, AR 4Division of Gastroenterology University of Arkansas for Medical Science Little Rock, AR
Genome-wide single nucleotide polymorphism-based assay for high-resolution epidemiological analysis of the methicillin-resistant Staphylococcus aureus hospital clone EMRSA-15
Authors: A. Holmes, G. McAllister, P.R. McAdam, S. Hsien Choi, K. Girvan, A. Robb, G. Edwards, K. Templeton, J.R. Fitzgerald
Journal: Clinical Microbiology and Infection (2013)
Divergent response profile in activated cord blood <scp>T</scp> cells from first‐born child implies birth‐order‐associated <i>in utero</i> immune programming
Authors: M. Kragh, J. M. Larsen, A. H. Thysen, M. A. Rasmussen, H. M. Wolsk, H. Bisgaard, S. Brix
Journal: Allergy (2015)

First-born children are at higher risk of developing a range of immune-mediated diseases. The underlying mechanism of 'birth-order effects' on disease risk is largely unknown, but in utero programming of the child's immune system may play a role.We studied the association between birth order and the functional response of stimulated cord blood T cells.Purified cord blood T cells were polyclonally activated with anti-CD3-/anti-CD28-coated beads in a subgroup of 28 children enrolled in the COPSAC2010 birth cohort. Expression levels of seven activation markers on helper and cytotoxic T cells as well as the percentage of CD4(+) CD25(+) T cells were assessed by flow cytometry. Production of IFN-γ, TNF-α, IL-17, IL-4, IL-5, IL-13, and IL-10 was measured in the supernatants.IL-10 secretion (P = 0.007) and CD25 expression on CD4(+) helper T cells (P = 0.0003) in the activated cord blood T cells were selectively reduced in first-born children, while the percentage of circulating CD4(+) CD25(+) cord blood T cells was independent of birth order.First-born infants display a reduced anti-inflammatory profile in T cells at birth. This possible in utero 'birth-order' T-cell programming may contribute to later development of immune-mediated diseases by increasing overall immune reactivity in first-born children as compared to younger siblings.
Pseudo-Obstruction of the Large Bowel
Authors: N V Addison
Journal: Journal of the Royal Society of Medicine (1983)

Thirty patients with acute pseudo-obstruction of the large bowel are presented, and the aetiology and diagnosis of this recognized clinical entity are described. Emergency barium enema examination is recommended in patients with symptoms and signs of large bowel obstruction. When no mechanical blockage is found a diagnosis of pseudo-obstruction can be made. The management of pseudo-obstruction is conservative, with nasogastic suction, intravenous fluids and the treatment of any associated condition such as cardiac failure and inflammatory conditions. The indications for surgery in pseudo-obstruction are discussed.
Clinical stage I carcinoma of the testis: a review.
Authors: C Y Fung, M B Garnick
Journal: Journal of Clinical Oncology (1988)

Significant advances in the management of disseminated carcinoma of the testis have had a tremendous influence on the management of all stages of disease, including both stage I and stage II. Because the disease is so uniformly curable in advanced forms, strategies have evolved for lower stages of disease to maximize curative potential with minimization of therapeutic intervention and potential long-term side effects. This review addresses issues of diagnosis and initial clinical staging of patients with stage I carcinoma of the testis. The usefulness of biological tumor markers and the accuracy, sensitivity, and specificity of radiographic imaging modalities are emphasized. The traditional treatment of stage I seminomas and nonseminomas includes the role of both radiation therapy and retroperitoneal lymph node dissection (RPLND). Treatment results and complications of each modality are also reviewed. The importance of orchiectomy followed by meticulous surveillance, as well as a critical analysis of prognostic features of subsequent locoregional or systemic relapse in patients with stage I testis cancer, focuses attention on changing concepts of this disease. The rationale underlying improved ability to stage patients meticulously and offer therapeutic intervention when necessary following orchiectomy, constitutes the focus of present and future clinical research. Such strategies are discussed in detail.
Second primary lung cancer in squamous NSCLC patients: The Nancy Biobank's database
Authors: Fotis D. Vlastos, Georgios Kaltsakas, Aris Anagnostopoulos, Nadine Martinet, Nickolaos G. Koulouris
Journal: European Respiratory Journal (2014)

Follow up in operated non small cell lung cancer is a debatable issue. The Nancy “Centre of Biologic Resources” is an ISO 9001–2000 certified biobank with biologic material and follow-up data from French lung cancer and mesothelioma patients, collected for the last 20 years. This allows for a survey of second primary lung cancer in squamous cell lung cancer patients. Therefore, we set out to investigate whether there is a relationship between tobacco consumption and the development of second primary lung cancer in operated patients with squamous NSCLC.  A cohort of 540 consecutive squamous NSCLC patients (stage: in situ-IIIA) who underwent surgery has been accrued from October 1989 to January 2007. Registered characteristics were age, gender, stage, tobacco consumption (pack·years), age of onset and quitting smoking, family history of malignancy and professional exposition.  Thirty nine of the patients (7%) developed second primary lung cancer. They had (mean±SD): age=64±9 y, pack·years=56±28 y, age of smoking onset=22±12 y, and duration of quitting smoking=3.6±5.9 y. Six of those patients had a family history of malignancy and nine had a professional exposition. Comparing the patients who developed second primary cancer to those that did not for the aforementioned characteristics, only the pack·years index was significantly different (p=0.017). Asbestos exposure in the patients who developed second primary lung cancer (18%) tended to be greater than in those who did not (8%) (p=0.076).  Tobacco consumption was greater among operated squamous NSCLC patients with second primary lung cancer comparing to those without second primary lung cancer. Follow up might be tighter for these patients.
Radiographic progression in rheumatoid arthritis: Does it reflect outcome? Does it reflect treatment?
Authors: D van der Heijde
Journal: Annals of the Rheumatic Diseases (2001)

Although there is clear face validity that structural damage is related to outcome, it is difficult to prove this. Recently, more evidence became available that structural damage, as assessed on plain films, is indeed related to disease activity in clinical trials and therefore can be used to assess the effect of treatment. Also, a relationship between structural damage and outcome, mainly defined as physical disability, was established. Several examples of findings in recent publications are presented which lead to the following conclusions. There is a relation between the response to treatment measured as clinical disease activity and measured as radiographic progression in most clinical therapeutic trials. A strong relation between local inflammation and progression of damage in the individual joint is present. This is robust evidence for the hypothesis that inflammation leads to structural damage. There is a good relation between the damage in small and large joints as assessed on plain films. Damage measured in small joints is a good substitute for overall damage. Disease activity is always strongly correlated with functional disability throughout the disease course. There is an increasing relation between disability and structural damage with increasing disease duration.
Suppression of Melanotroph Carcinogenesis Leads to Accelerated Progression of Pituitary Anterior Lobe Tumors and Medullary Thyroid Carcinomas in <i>Rb</i>+/− Mice
Authors: Zongxiang Zhou, Andrea Flesken-Nikitin, Corinna G. Levine, Elena N. Shmidt, Jessica P. Eng, Ekaterina Yu. Nikitina, David M. Spencer, Alexander Yu. Nikitin
Journal: Cancer Research (2005)

Abstract Mice with a single copy of the retinoblastoma gene (Rb+/−) develop a syndrome of multiple neuroendocrine neoplasia. They usually succumb to fast-growing, Rb-deficient melanotroph tumors of the pituitary intermediate lobe, which are extremely rare in humans. Thus, full assessment of Rb role in other, more relevant to human pathology, neoplasms is complicated. To prevent melanotroph neoplasia while preserving spontaneous carcinogenesis in other types of cells, we have prepared transgenic mice in which 770-bp fragment of pro-opiomelanocortin promoter directs expression of the human RB gene to melanotrophs (TgPOMC-RB). In three independent lines, transgenic mice crossed to Rb+/− background are devoid of melanotroph tumors but develop the usual spectrum of other neoplasms. Interestingly, abrogation of melanotroph carcinogenesis results in accelerated progression of pituitary anterior lobe tumors and medullary thyroid carcinomas. A combination of immunologic tests, cell culture studies, and tumorigenicity assays indicates that α-melanocyte–stimulating hormone, which is overproduced by melanotroph tumors, attenuates neoplastic progression by decreasing cell proliferation and inducing apoptosis. Taken together, we show that cell lineage–specific complementation of Rb function can be successfully used for refining available models of stochastic carcinogenesis and identify α-melanocyte–stimulating hormone as a potential attenuating factor during progression of neuroendocrine neoplasms.
Thyroid Carcinoma, Version 2.2014
Authors: R. Michael Tuttle, Robert I. Haddad, Douglas W. Ball, David Byrd, Paxton Dickson, Quan-Yang Duh, Hormoz Ehya, Megan Haymart, Carl Hoh, Jason P. Hunt, Andrei Iagaru, Fouad Kandeel, Peter Kopp, Dominick M. Lamonica, William M. Lydiatt, Judith McCaffrey, Jeffrey F. Moley, Lee Parks, Christopher D. Raeburn, John A. Ridge, Matthew D. Ringel, Randall P. Scheri, Jatin P. Shah, Steven I. Sherman, Cord Sturgeon, Steven G. Waguespack, Thomas N. Wang, Lori J. Wirth, Karin G. Hoffmann, Miranda Hughes
Journal: Journal of the National Comprehensive Cancer Network (2014)

These NCCN Guidelines Insights focus on some of the major updates to the 2014 NCCN Guidelines for Thyroid Carcinoma. Kinase inhibitor therapy may be used to treat thyroid carcinoma that is symptomatic and/or progressive and not amenable to treatment with radioactive iodine. Sorafenib may be considered for select patients with metastatic differentiated thyroid carcinoma, whereas vandetanib or cabozantinib may be recommended for select patients with metastatic medullary thyroid carcinoma. Other kinase inhibitors may be considered for select patients with either type of thyroid carcinoma. A new section on "Principles of Kinase Inhibitor Therapy in Advanced Thyroid Cancer" was added to the NCCN Guidelines to assist with using these novel targeted agents.
Optimizing sharing of hospital biobank samples
Authors: Peter H. J. Riegman, Bas de Jong, Maria Grazia Daidone, Tommy Söderström, James Thompson, Jacqueline A. Hall, Maimuna Mendy, Jelle ten Hoeve, Annegien Broeks, Wenche Reed, Manuel M. Morente, José Antonio López-Guerrero, V. Peter Collins, Jane Rogan, Ulrik Ringborg
Journal: Science Translational Medicine (2015)

Implementing technical guidelines and standards as well as ways to boost cooperation should facilitate sharing of hospital biobank samples.
Abstract 108: Interleukins 17 A and 22 in diabetic patients with stable coronary artery disease
Authors: Dinaldo C Oliveira, Elayne Heide, Moacyr Rego, Viviane R Gomes, Danielle G Oliveira, Maira G Pita
Journal: Circulation Research (2014)

Introduction: The role of the immune and inflammatory pathways in diabetic patients with coronary artery disease (CAD) is important but not complete understood. The aim of this study was to evaluate concentrations of the interleukins 17 A and 22 in diabetic patients with stable CAD. Hypothesis: Interleukins 17 A and 22 are not increased in diabetic patients with stable CAD. Methods: This is a cross-sectional, prospective, analytical study, conducted from August to December 2012. We included 15 diabetic patients (P) with stable CAD, CCS III or IV, ischemic myocardial scintigraphy, who had not been subjected to any kind of myocardial revascularization and with coronary stenosis ≥ 50% according to current coronary angiography. There were 20 healthy volunteers (C), to take up comparison of concentrations of interleukins (IL). Interleukins were evaluated in serum of patients and after 48 hours of cells in culture with and without stimulus. IL concentrations were expressed in pg / ml. Statistical analysis was performed using the Mann-Whitney or Student t test. P ≤ 0,05 was considered statistically significant. Results: There were 6 men and 9 women in the group of the diabetic patients and 12 men and 8 women in the controls. The age was similar between the groups (61.6 ± 6.7 years vs 57.9 ± 9.4, p = ns). The main CAD risk factors: hypertension 73%, smoking 60%, dyslipidemia 40%, prior myocardial infarction 33%. The comparison between the groups showed: IL 17 A: Serum: P = 3.91 (3.91 -- 3.91 ) vs C = 3.91 (3.91 -- 3.91 ), p = 0.82; culture 48 hours without stimulus: P = 3.91 (3.91 -- 3.91) vs C = 3.91 (3.91 -- 3.91), p = 0.06; culture 48 hours with stimulus: P = 199 (3.91 -- 520) vs C = 154 (3.91 -- 574), p = 0.90. IL 22: Serum: P = 15.63 (15.63 -- 41.09) vs C = 15.63 (15.63 -- 41.09), p = 0.34; culture 48 hours without stimulus: P = 7.81 (7.81 -- 7.81) vs C = 7.81 (7.81 -- 7.81), p = 0.09; culture 48 hours with stimulus: P = 113.79 (7.81 - 248.63) vs C = 322.87 (7.81 - 628.49), p = 0.14. Conclusions: There were no differences in concentrations of IL 17 A and 22, does not matter in serum or cell in culture. In conclusion in diabetic patients with stable CAD the concentrations of interleukins 17 A and 22 were not increased.
Provoked Coronary Spasm Predicts Adverse Outcome in Patients With Acute Myocardial Infarction
Authors: Kohei Wakabayashi, Hiroshi Suzuki, Yuki Honda, Daisuke Wakatsuki, Keisuke Kawachi, Kei Ota, Shinji Koba, Nobuyuki Shimizu, Fuyuki Asano, Tokutada Sato, Youichi Takeyama
Journal: Journal of the American College of Cardiology (2008)
Armchairs and Bow Ties
Authors: Sara Catherine LaHue
Journal: JAMA (2015)

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Modulation of PD-1 and PD-L1 expression in response to acute viral infection of human lung tissue
Authors: Richard McKendry, Karl Staples, C. Mirella Spalluto, Tom Wilkinson
Journal: European Respiratory Journal (2014)

Introduction and Objectives: Acute viral infections are common in healthy individuals without long-term health implications, but these infections can have more serious outcomes for infants, the elderly and immunocompromised individuals. Patients with chronic respiratory conditions, such as COPD, are at greater risk from severe adverse effects of acute respiratory infection. Investigation of how pulmonary immune cells of healthy and COPD patients differ in their responses to viral infection may elucidate defective mechanisms of host defense and allow for intervention to aid disease resolution.

Methods: Human lung tissue from control or COPD patients undergoing lung resection surgery was infected with H3N2 strain X31 Influenza A virus (3V Biosciences, CA) or UV-irradiated X31 virus. Tissue was digested using collagenase to generate a single-cell suspension and was labelled with fluorescent antibodies for FACS analysis. The expression of the activation and exhaustion marker PD-1 was analysed on T cells, with the ligand PD-L1 measured on epithelial cells and macrophagess.

Results : Proportion of CD4 T cells (mean=3.9%) and CD8 T cells (mean=10.9%) expressing PD-1 is greater in COPD individuals at baseline levels compared to controls (CD4 mean=1.2%, CD8 mean=2.4%). This baseline difference impacts upon PD-1 upregulation in response to X31 infection. Macrophages upregulate PD-L1 in response to infection in both COPD (1.2% to 6.6%, p=0.03) and control (1.3% to 16.6%, p=0.03) samples.

Conclusion: Macrophages may play a role in controlling T cell responses to acute viral infection. This effect may be lost with high levels of PD-1 expression in COPD patients independently of X31 infection.
The influence of symptoms of disease and side effects of treatment on compliance with cancer therapy.
Authors: J L Richardson, G Marks, A Levine
Journal: Journal of Clinical Oncology (1988)

To provide a systematic analysis of how adverse symptoms of disease and side effects of cancer therapy relate to patient noncompliance with treatment, we interviewed 107 patients with hematologic malignancies at the initiation of therapy and 6 months later to collect information on the type, frequency, and difficulty of unpleasant physical effects experienced. Level of compliance was monitored (biochemically and with self-report) on a monthly basis for oral self administration of allopurinol and prednisone. Appointment-keeping to receive infused chemotherapy was also monitored. Nausea was the most frequent side effect experienced. Nausea, fever, and pain were the most difficult physical effects to tolerate when they occurred. Complex treatment regimens and severe diseases related to reports of more physical effects. Younger patients had a more difficult time dealing with these effects than did older patients. Neither the occurrence, frequency, or difficulty dealing with any of the effects related to noncompliance with either of the two self-administered medications. Difficulty with particular effects did relate to noncompliance with clinic appointments to receive infused chemotherapy.
More Nuanced Informed Consent Is Not Necessarily Better Informed Consent
Authors: Danielle Hornstein, Sharon Nakar, Sara Weinberger, Dov Greenbaum
Journal: The American Journal of Bioethics (2015)

In the era of Big Data, even a little information can go a long way in partially or wholly identifying anonymous individuals and/or disclosing their private and personal information. In a well-docu...
HIF Hydroxylase Pathways in Cardiovascular Physiology and Medicine
Authors: Tammie Bishop, Peter J. Ratcliffe
Journal: Circulation Research (2015)

Hypoxia inducible factors (HIFs) are α/β heterodimeric transcription factors that direct multiple cellular and systemic responses in response to changes in oxygen availability. The oxygen sensitive signal is generated by a series of iron and 2-oxoglutarate–dependent dioxygenases that catalyze post-translational hydroxylation of specific prolyl and asparaginyl residues in HIFα subunits and thereby promote their destruction and inactivation in the presence of oxygen. In hypoxia, these processes are suppressed allowing HIF to activate a massive transcriptional cascade. Elucidation of these pathways has opened several new fields of cardiovascular research. Here, we review the role of HIF hydroxylase pathways in cardiac development and in cardiovascular control. We also consider the current status, opportunities, and challenges of therapeutic modulation of HIF hydroxylases in the therapy of cardiovascular disease.
Human Isolated Airway Contraction
Authors: ETIENNE ROUX, JEAN-MARC HYVELIN, JEAN-PIERRE SAVINEAU, ROGER MARTHAN
Journal: American Journal of Respiratory and Critical Care Medicine (1999)

Although there is epidemiological evidence that an increase in allergic diseases such as asthma may be linked to air pollution, there is little experimental data to address this issue. The aim of this study was thus to investigate the interaction between passive sensitization and exposure to pollutants in human isolated airways. We have examined (1) the effect of a preexposure to pollutants on the contraction of sensitized bronchi to a specific antigen, and (2) the effect of passive sensitization on the contraction to nonspecific agonists in bronchi preexposed to pollutants. In tissues sensitized by incubation in sera from asthmatic patients, preexposure to 0.3 μ M acrolein (an aldehyde) for 10 min or 20 min significantly increased the maximal contractile response to the antigen Dermatophagoides pteronyssinus (D. pter.) by 20.5 ± 6.5 and 34.9 ± 7.4%, respectively. Similarly, preexposure to ozone (1 ppm for 20 min) increased the response to D. pter. by 25.3 ± 11.3%. On the other hand, passive sensitization increased the contractile response to carbachol or histamine of bronchial rings preexposed to 0.3 μ M acrolein for 10 min by 33.5 ± 6.2% and 32.5 ± 5.1%, respectively. This study provides a proof of principle in vitro for a combined effect of immunological sensitization and exposure to pollutants, i.e., passive sensitization and exposure to pollutants act in a synergistic manner on human bronchial smooth muscle reactivity in response to both specific antigen and nonspecific agonists.