tbuckley/cabot-search huggingface dataset:
THE MODERN APPLICATION OF THE ROMAN SYSTEM OF HEATING BUILDINGS
Authors: D. F. Harris
Journal: BMJ (1924)

IF there is onec thiing certain about the life of the Romans, both in.their own country and in this, it is that they heated their houses and the water for their baths.The recent unicoverinlg of a Roman dwelling at Folkestone in whichl the hypocaust is well preserved has reminded us of the pains the Romanis took to warm the floors of their houses by the products of the combustion of a furnace passing continuously below them.But they did more than that, for they warmed the walls by means of hot air passed through hiollow bricks built into the interior.The floor of a Romiian house, in fact, was not laid on the ground, but on the top of a large niumber of low pillars composed of tiles- flat bricks-or stones, arounid alnid between which the lot air circulated.
Predicting future disease course in Crohn’s disease by colonoscopy or magnetic resonance: which is the crystal ball?
Authors: Silvio Danese, Laurent Peyrin-Biroulet, Gionata Fiorino
Journal: Gut (2015)

Crohn's disease (CD) is a chronic and progressive condition leading to cumulative bowel damage overtime, mainly related to stricturing or penetrating lesions. About half of patients with CD require surgical intestinal resection 10 years after diagnosis.1 Importantly, the development of disease complications (stricture, fistula and/or abscess) is known to be the main indication for surgery in these patients.1 The identification of factors associated with a higher need for surgery for CD is a prerequisite to the development of therapeutic strategies potentially altering disease course, with the final aim of preventing undertreatment and avoiding overtreatment with biologics.

Clinical risk factors are insufficient to predict disease course,2 and there is a well-known disconnect between clinical symptoms and endoscopic disease activity.3 Hence, we need to look beyond clinical symptoms. Accumulating evidence indicates that mucosal healing may change the natural course of the disease by decreasing the need for surgery and reducing hospitalisation rates in CD.4 However, no controlled trials addressed this question and only indirect evidence is available. Furthermore, CD is a transmural disease, and endoscopy, which is still the gold standard for assessing disease activity in CD, cannot detect the presence of bowel damage. Over the last decade, cross-sectional imaging techniques, such as MRI, CT and ultrasound, have …
Does exercise reduce all-cancer death rates?
Authors: R J Shephard
Journal: British Journal of Sports Medicine (1992)

A reanalysis is made of earlier data relating to initial physical fitness and the likelihood of death from all forms of cancer. It is argued that the original analysis may have been biased by an association between initial fitness and other health habits, particularly cigarette smoking. The association with fitness status remains after reanalysis of the data on the assumption that current smoking leads to a uniform doubling of the risk of cancer death, but the effect is weaker than previously reported. There remains some potential bias, in that the quantity of current smoking may have been linked to fitness status. Some 55% of deaths were untraced, but it is argued that any socioeconomic or other bias from this cause is likely to account for the association between cancer risk and low fitness status. Any reduction of cancer risk is associated with the change from an extremely sedentary to a moderately sedentary lifestyle. It thus cannot be explained in terms of the mechanisms previously invoked to explain low risks of colonic and reproductive cancers in endurance athletes.
Definitive and Adjuvant Radiotherapy in Locally Advanced Non–Small-Cell Lung Cancer: American Society of Clinical Oncology Clinical Practice Guideline Endorsement of the American Society for Radiation Oncology Evidence-Based Clinical Practice Guideline
Authors: Andrea Bezjak, Sarah Temin, Gregg Franklin, Giuseppe Giaccone, Ramaswamy Govindan, Melissa L. Johnson, Andreas Rimner, Bryan J. Schneider, John Strawn, Christopher G. Azzoli
Journal: Journal of Clinical Oncology (2015)

The American Society for Radiation Oncology (ASTRO) produced an evidence-based guideline on external-beam radiotherapy for patients with locally advanced non-small-cell lung cancer (NSCLC). Because of its relevance to the American Society of Clinical Oncology (ASCO) membership, ASCO endorsed the guideline after applying a set of procedures and a policy that are used to critically examine and endorse guidelines developed by other guideline development organizations.The ASTRO guideline was reviewed by ASCO content experts for clinical accuracy and by ASCO methodologists for developmental rigor. On favorable review, an ASCO expert panel was convened and endorsed the guideline. The ASCO guideline approval body, the Clinical Practice Guideline Committee, approved the final endorsement.The recommendations from the ASTRO guideline, published in Practical Radiation Oncology, are clear, thorough, and based on the most relevant scientific evidence. The ASCO Endorsement Panel endorsed the guideline and added qualifying statements.For curative-intent treatment of locally advanced NSCLC, concurrent chemoradiotherapy improves local control and overall survival compared with sequential chemotherapy followed by radiation. The standard dose-fractionation of radiation is 60 Gy given in 2-Gy once-daily fractions over 6 weeks. There is no role for the routine use of induction therapy before chemoradiotherapy. Current data fail to support a clear role for consolidation therapy after chemoradiotherapy; however, consolidation therapy remains an option for patients who did not receive full systemic chemotherapy doses during radiotherapy. Important questions remain about the ideal concurrent chemotherapy regimen and optimal management of patients with resectable stage III disease.
Evolutionary Expansion and Specialization of the PDZ Domains
Authors: O. Sakarya, C. Conaco, O. Egecioglu, S. A. Solla, T. H. Oakley, K. S. Kosik
Journal: Molecular Biology and Evolution (2009)

PDZ domains are protein–protein interaction modules widely used to assemble membranous signaling complexes including those found in the neuronal synapse. PDZ-containing genes encoded in metazoan genomes vastly outnumber those in prokaryotes, plants, and fungi. By comparing 40 proteomes to track the evolutionary history of the PDZ domain, we observed that the variety of associations between PDZ and other domains expands greatly along the stem leading to metazoans and choanoflagellates. We asked whether the expansion of PDZ domains was due to random or specific sequence changes. Studying the sequence signatures of 58 PDZ lineages that are common to bilaterian animals, we showed that six common amino acid residues are able to classify 96% of PDZ domains to their correct evolutionary lineage. In PDZ domain–ligand cocrystals, four of these "classifying positions" lie in direct contact with the −1 and −3 residues of the ligand. This suggests coevolution of the more flexible regions of the binding interaction as a central mechanism of specialization inherent within the PDZ domain. To identify these positions, we devised two independent algorithms—a metric termed within-clade entropy (WCE) and an average mutual information (AvgMI) score—that both reached similar results. Extending these tools to the choanoflagellate, Monosiga brevicollis, we compared its PDZ domains with their putative metazoan orthologs. Interestingly, the M. brevicollis genes lack conservation at the classifying positions suggesting dissociation between domain organization in multidomain proteins and specific changes within the PDZ domain.
Aldehyde Dehydrogenase Activation Prevents Reperfusion Arrhythmias by Inhibiting Local Renin Release From Cardiac Mast Cells
Authors: Kenichiro Koda, Mariselis Salazar-Rodriguez, Federico Corti, Noel Yan-Ki Chan, Racha Estephan, Randi B. Silver, Daria Mochly-Rosen, Roberto Levi
Journal: Circulation (2010)

Background— Renin released by ischemia/reperfusion from cardiac mast cells activates a local renin-angiotensin system (RAS). This exacerbates norepinephrine release and reperfusion arrhythmias (ventricular tachycardia and fibrillation), making RAS a new therapeutic target in myocardial ischemia. Methods and Results— We investigated whether ischemic preconditioning (IPC) prevents cardiac RAS activation in guinea pig hearts ex vivo. When ischemia/reperfusion (20 minutes of ischemia/30 minutes of reperfusion) was preceded by IPC (two 5-minute ischemia/reperfusion cycles), renin and norepinephrine release and ventricular tachycardia and fibrillation duration were markedly decreased, a cardioprotective anti-RAS effect. Activation and blockade of adenosine A 2b /A 3 receptors and activation and inhibition of protein kinase Cε (PKCε) mimicked and prevented, respectively, the anti-RAS effects of IPC. Moreover, activation of A 2b /A 3 receptors or activation of PKCε prevented degranulation and renin release elicited by peroxide in cultured mast cells (HMC-1). Activation and inhibition of mitochondrial aldehyde dehydrogenase type-2 (ALDH2) also mimicked and prevented, respectively, the cardioprotective anti-RAS effects of IPC. Furthermore, ALDH2 activation inhibited degranulation and renin release by reactive aldehydes in HMC-1. Notably, PKCε and ALDH2 were both activated by A 2b /A 3 receptor stimulation in HMC-1, and PKCε inhibition prevented ALDH2 activation. Conclusions— The results uncover a signaling cascade initiated by A 2b /A 3 receptors, which triggers PKCε-mediated ALDH2 activation in cardiac mast cells, contributing to IPC-induced cardioprotection by preventing mast cell renin release and the dysfunctional consequences of local RAS activation. Thus, unlike classic IPC in which cardiac myocytes are the main target, cardiac mast cells are the critical site at which the cardioprotective anti-RAS effects of IPC develop.
Markers of airway remodeling in young adults with clinical remission of asthma
Authors: Sian Evans
Journal: European Respiratory Journal (2013)

Background: Airway wall remodeling has been described in young adults with asthma persisting from childhood. We aimed to compare markers of remodeling between young adults from the Isle of Wight Birth Cohort with clinical remission of asthma (RA) and clinically persistent asthma (PA) against healthy controls (HC)

Methods : Bronchial biopsies were analysed for Collagen I and Collagen III deposition within the submucosa. Collagen band thickness (CBT) was measured in biopsies with well-orientated epithelium. Data was analysed using non-parametric methods.

Results : Collagen I was increased in subjects with PA compared with HC (p=0.007); those with RA showed an intermediate level of Collagen I. Collagen III was highest in those with PA (vs RA p=0.017; vs HC p<0.001) and those with RA showed a lower level but still significantly higher than HC (p<0.035). Mean CBT was higher in those with PA and RA than HC (p<0.001 and p=0.001 respectively)

![Figure][1] 



Conclusion : Markers of remodelling are still visible in subjects with clinical remission of asthma. They have persistent CBT thickening similar to those subjects with clinically persistent asthma and significantly higher levels of Collagen III than healthy controls but less than those with persistent asthma. This would suggest that collagen band changes are non-reversible whereas submucosal expression of Collagens I and III remit with symptoms.

 [1]: pending:yes
Isobutyramide therapy in patients with sickle cell anemia
Authors: A. W. Saleh, A. Van Goethem, R. Jansen, H. J. R. Velvis, L.‐H. Gu, T. H. J. Huisman
Journal: American Journal of Hematology (1995)

Abstract We have administered Isobutyramide as a suspension over a period of 3 months, from a starting dose of 50 mg/kg/day up to 150 mg/kg/day, to four adult sickle cell (SS) anemia patients. The maximum dose was maintained for 3 weeks. The blood counts remained stable and the Hb F levels decreased slightly. The G γ levels increased at the end of the trial, suggesting activation of the G γ gene at the highest dose of Isobutyramide. Three patients showed a stable rate of hemolysis, while in one patient, an increase of lactate dehydrogenase occurred. None of the patients experienced pain crisis or organ‐specific crisis, but all four complained about mild epigastric burning and a bitter taste. After the first month of treatment one patient complained about intolerable epigastric discomfort which was relieved by Omeprazole. Another patient complained about increasing dyspepsia in the 12th week leading to the termination of the trial. Oral Isobutyramide administration does not qualify as an effective treatment of SS patients. © 1995 Wiley‐Liss, Inc.
Identification and characterization of pro-T lymphocytes and lineage-uncommitted lymphocyte precursors from mice with three novel surface markers.
Authors: R Palacios, J Samaridis, D Thorpe, T Leu
Journal: The Journal of Experimental Medicine (1990)

The study of prethymic stages of T cell development has been limited because specific markers for mouse pro-T lymphocytes were not available. We developed a panel of rat monoclonal antibodies (mAbs) that bind to our pro-T lymphocyte clones obtained from bone marrow of young adult mice and the thymus of 14-d-old embryos. The mAbs, called Joro 30-8, Joro 37-5, and Joro 75, were found to bind to all pro-T clones tested but not to cell lines representing later stages of T cell development, B lymphocyte, or myeloid lineages. We determined the frequency and tissue distribution in normal and immunodeficient mouse strains as well as the ontogeny in liver and thymus of cells positive for these mAbs. The results were consistent with the pattern of reactivity observed with cell lines. We isolated Joro 30-8+, Joro 37-5+, and Joro 75+ bone marrow cells by cell sorter and found that: (a) phenotypically, they are Thy-1+, CD4-, CD8-, CD3-, B-220-, IgM-, F4/80-, and PgP-1+; (b) they grew in response to the combination of interleukin 3 (IL-3) + IL-4 or IL-3 + IL-4 + IL-6; and (c) Joro 37-5+ and Joro 75+ marrow cells gave rise to mature T lymphocytes but not to B lymphocytes, while Joro 30-8+ marrow cells generated both T and B lymphocytes after 8-12 wk of transfer into severe combined immunodeficient (Scid) mice. In normal mice subjected to 600 rad of irradiation to induce a wave of thymus recolonization, we found by flow fluorocytometry analysis that Joro+ cells entered the thymus 2 d after irradiation, expanded during the next 4 d, and underwent further differentiation, and from day 8 up to day 21, post-irradiation Joro+ cells were no longer detectable in the thymuses. Immunohistochemical analysis of normal thymus shows the presence of very few Joro 30-8+, Joro 37-5+, and Joro 75+ lymphoid cells in the subcapsular area and outer cortex but not in the medulla. The kinetic analysis of tissue sections from thymuses at various days post-irradiation suggests that Joro+ cells enter the thymus via blood vessels through the subcapsular and outer cortex areas; subsequently, these cells seem to migrate to the inner cortex without reaching the medulla, and give rise to Joro- thymocytes.(ABSTRACT TRUNCATED AT 400 WORDS)
Healthcare Resource Utilization (Hcru) in Patients Receiving Ipilimumab for Advanced Melanoma: Impact of Survival and Eastern Cooperative Oncology Group (Ecog) Status
Authors: A. Tarhini, A.S. Rao, S. Corman, M. Botteman, S. Mehta, X. Ji, M. Katyal, K. Margolin
Journal: Annals of Oncology (2014)
Immunomediated and Ischemia-Independent Inflammation of Coronary Microvessels in Unstable Angina
Authors: Gian Gastone Neri Serneri, Maria Boddi, Pietro Amedeo Modesti, Ilaria Cecioni, Mirella Coppo, Maria Letizia Papa, Thomas Toscano, Antonio Marullo, Mario Chiavarelli
Journal: Circulation Research (2003)

This study investigated whether the myocardium is involved in the acute inflammatory reaction associated with bursts of unstable angina (UA). We looked for the presence of activated DR+ inflammatory cells and the expression patterns, localization, and immunostaining identification of genes for cytokines (IL-1beta, TNF-alpha, IL-6, and IFN-gamma), MCP-1, and iNOS in the left ventricle biopsies from 2-vessel disease anginal patients, 24 with UA and 12 with stable angina (SA), who underwent coronary bypass surgery. Biopsy specimens from 6 patients with mitral stenosis who underwent valve replacement were examined as control hearts (CHs). Plasma levels of IL-2 soluble receptor (sIL-2R) were measured as a marker of systemic immune reaction. In CHs, DR+ cells were undetectable, and cytokine and iNOS mRNA expression were negligible. UA patients had higher sIL-2R levels than SA patients (P<0.01), and their biopsy specimens showed both numerous DR+ cells identified as lymphocytes, macrophages, endothelial cells, and elevated expression levels of cytokine and iNOS genes (from 2.4- to 6.1-fold vs SA; P<0.01). Cytokine and iNOS genes and proteins were localized in endothelial cells without involvement of myocytes. IL-1beta and MCP-1 mRNAs were nearly undetectable. No significant differences were found in the number of DR+ cells, levels of cytokine, and iNOS genes between potentially ischemic and nonischemic left ventricle areas. In SA specimens, DR+ cells were very rare and only mRNAs for TNF-alpha and iNOS genes were overexpressed versus CHs. These results indicated that an acute immunomediated inflammatory reaction, essentially involving coronary microvessels, is demonstrable in UA patients.
Radiological manifestations of ankylosing spondylitis according to age at onset.
Authors: M J Riley, B M Ansell, E G Bywaters
Journal: Annals of the Rheumatic Diseases (1971)

Although ankylosing spondylitis usually starts in the third decade of life, in both men and women, Wilkinson and Bywaters (1958) found that in 18 per cent. of 222 cases the onset occurred in the second decade (the earliest being at 11 years) and that in 11 per cent.the disease apparently started after the age of 39 years: five patients were seen with symptoms apparently starting at the age of 50 years or more.We noted that disc degeneration might sometimes 'precede ossification, giving an appearance resem- bling osteophytosis'; this created difficulty in reading the spinal x rays, particularly in these more elderly patients.We have returned to the problem of differing radiological manifestations in different 'age-at-onset' groups because we felt that such a study might throw light on the pathogenesis of the various lesions seen.As Collins (1949) insisted, an osteophyte is essentially an outgrowth of new subperiosteal bone at the vertebral margin, second- ary to the anterolateral prolapse of a degenerated disc, but he regarded a syndesmophyte as 'an ossification of the outer fibres of the annulus fibrosus'.de Seze, Lacapere, and Amoudruz (1952), in their insistence on the subligamentary location of both, have drawn attention to the osteophyte-like appearance-'like a parrot's beak' of the so-called 'syndesmophyte' in patients with spondylitis of late onset.
Association of Overexpression of Tumor Suppressor Protien p53 With Rapid Cell Proliferation and Poor Prognosis in Node-Negative Breast Cancer Patients
Authors: J. Isola, T. Visakorpi, K. Holli, O.-P. Kallioniemi
Journal: JNCI Journal of the National Cancer Institute (1992)

Recent evidence indicates that a subset of axillary node-negative (ANN) breast cancer patients can benefit from adjuvant therapy. Reliable prognostic markers are needed, however, to help clinicians identify these patients and arrive at more rational treatment decisions.Mutations of the p53 tumor suppressor gene often result in overexpression of the p53 protein. In this study, we evaluated the prognostic significance of p53 protein overexpression in patients with ANN breast cancer. We also studied the association between the tumor cell proliferation rate and overexpression of the p53 and c-erbB-2 proteins, both of which have been implicated in cell cycle control. The c-erbB-2 protein is the product of the ERBB2 gene.Two hundred eighty-nine ANN cases were randomly selected from a population-based cohort of patients who had not received any kind of adjuvant chemotherapy or endocrine therapy. Overexpression of the p53 and c-erbB-2 proteins was studied immunohistochemically in archival paraffin-embedded tumor samples, using the CM-1 polyclonal and the TAb 250 monoclonal antibodies, respectively. The tumor cell proliferation rate was measured as the S-phase fraction by DNA flow cytometry. Statistical analyses were performed using BMDP software.High-level p53 protein overexpression, found in 41 of the 289 tumors, was most common in tumors with high histologic grade, negative estrogen receptor status, c-erbB-2 protein overexpression, DNA index greater than 1.3, or high S-phase fraction. The lowest S-phase levels were found in tumors with neither p53 nor c-erbB-2 protein overexpression; the highest levels were seen in tumors showing overexpression of both proteins (P less than .0001). Both p53 and c-erbB-2 overexpression, as well as tumor size, had independent prognostic value in multivariate analysis. Eight-year survival of patients with p53 protein overexpression was 56% compared with 81% in patients with no overexpression (relative risk, 3.7; P less than .0001). If the S-phase fraction was included in a Cox regression analysis, however, only the tumor size and the S-phase fraction emerged as independent predictors of survival.Overexpression of the p53 and c-erbB-2 proteins indicates a high malignant potential in ANN breast cancer, but it is not a significant prognostic factor independent of the cell proliferation rate. The correlation between overexpression of these proteins and an increased S-phase fraction suggests that they may confer a proliferative advantage to cancer cells in vivo.
Opioid Peptides and Opioid Receptors in Cells of the Immune System
Authors: N E S Sibinga, A Goldstein
Journal: Annual Review of Immunology (1988)

I Abbreviations used: ACTH, adrenocorticotropic hormone; ADCC, antibody-dependent cellular cytotoxicity; Bma .. total number of binding sites; BREM, bremazocine, an agonist with modest selectivity for K sites; CCK, cholecystokinin; ConA, concanavalin A; DADLE, [D-Ala2,D-LeuS]enkephalin, an agonist somewhat selective for /j �ites; DEX, dextrorphan, inert enantiomer of LEV; DHM, dihydromorphine, a Jl-selective agonist; DIP, dipre­ norphine, a relatively nonselective antagonist; DYN, dynorphin, a peptide product of the dynorphin gene, selective for K sites; EKC, ethylketazocine, a benzomorphan agonist with modest selectivity for K sites; END, endorphin; a peptide product of the pro-opio­ melanocortin gene; <Xand y-endorphin are fragments of fJ-endorphin; fJ-endorphin is selective for e sites; ETO, etorphine, a relatively nonselective agonist; fMLP, formyl-methio­ nyl-leucinyl-phenylalanine; granulo, granulocyte(s); h, human; ICso, concentration of a com­ peting ligand that reduces specific binding of radioligand by 50%; icv, intracerebro­ ventricular; IFN, interferon; ir-, immunoreactive; Kd, K;, equilibrium dissociation con­ stants, determined by binding isotherm or by competition, respectively; LENK, [Leu]en­ kephalin, a minor product of the pro-enkephalin gene, an agonist somewhat selective for {) sites; leuko, leukocyte(s); LEV, levorphanol, a Jl-selective agonist; Iympho, Iymphocyte(s); m, mouse; M.p, macrophage(s); MENK, [Met]enkephalin, major product of the pro-enkephalin gene, a /j-selective agonist; MNC, mononuclear cell(s); mono, monocyte(s); MOR, morphine, a Jl-selective agonist; NA, not applicable; NAL, naloxone, a moderately jl-selective antag­ onist; NK, natural killer; NR, not reported; NTX, naltrexone, a long-lasting Jl-selective antagonist closely related to naloxone; PBL, peripheral blood Iymphocyte(s); PBMNC, peripheral blood mononuclear cell(s); PHA, phytohemagglutinin; PMNL, polymorpho­ nuclear leukocyte(s); r, rat; RIA, radioimmunoassay; spleno, splenocyte; SRBC, sheep red blood cells; VIP, vasoactive intestinal peptide.