tbuckley/cabot-search huggingface dataset:
THE INCIDENCE AND PATHOGENESIS OF MYOCARDITIS IN RABBITS AFTER GROUP A STREPTOCOCCAL PHARYNGEAL INFECTIONS
Authors: Robert J. Glaser, Wilbur A. Thomas, Stephen I. Morse, James E. Darnell
Journal: The Journal of Experimental Medicine (1956)

Rabbits subjected to single pharyngeal infections with group A streptococci developed cardiac lesions characterized by myofiber necrosis and a non-granulocytic cellular reaction with histiocytes, lymphocytes, and Anitschkow myocytes. The histopathologic changes were demonstrable in some animals within 24 hours of inoculation, apparently were maximal 72 hours after induction of infection (at which time they were seen in the hearts of all nine rabbits studied), and thereafter healed in the course of the following 2 weeks. The extent of involvement was variable, and with healing the necrotic areas were replaced by fibrous tissue. When intradermal infections with the same organisms were produced in rabbits, cardiac lesions, indistinguishable from those observed in the pharyngeally infected group, appeared in a much smaller number of animals. The hearts of five of six rabbits sacrificed a month or more following the last of a series of streptococcal pharyngeal infections exhibited lesions characterized chiefly by fibrosis, although mononuclear cellular infiltrations were also noted. In these repetitively infected animals the presence of occasional multinucleated giant cells and a few small foci of calcification were features not encountered in the single infection group. In a second series of rabbits sacrificed 3 days after the last of three pharyngeal infections with different strains of streptococci, acute as well as more chronic changes were observed. In none of the lesions in rabbits subjected to single or multiple streptococcal infections were bacteria demonstrable, either in histologic sections or in cultures of myocardial tissue. A large number of control animals was studied concomitantly, and in only one instance was a lesion, considered comparable to those described in the streptococcal series, encountered. The implications of these findings, particularly in terms of the non-suppurative sequelae of streptococcal infections in man, are discussed.
Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer
Authors: Lorena Alonso-Alconada, Laura Muinelo-Romay, Kadri Madissoo, Antonio Diaz-Lopez, Camilla Krakstad, Jone Trovik, Elisabeth Wik, Dharani Hapangama, Lieve Coenegrachts, Amparo Cano, Antonio Gil-Moreno, Luis Chiva, Juan Cueva, Maria Vieito, Eugenia Ortega, Javier Mariscal, Eva Colas, Josep Castellvi, Maite Cusido, Xavier Dolcet, Hans W Nijman, Tjalling Bosse, John A Green, Andrea Romano, Jaume Reventos, Rafael Lopez-Lopez, Helga B Salvesen, Frederic Amant, Xavier Matias-Guiu, Gema Moreno-Bueno, Miguel Abal
Journal: Molecular Cancer (2014)

About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in high-risk EC patients. CTC isolation was carried out in peripheral blood samples from 34 patients, ranging from Grade 3 Stage IB to Stage IV carcinomas and recurrences, and 27 healthy controls using two methodologies. Samples were subjected to EpCAM-based immunoisolation using the CELLection™ Epithelial Enrich kit (Invitrogen, Dynal) followed by RTqPCR analysis. The phenotypic determinants of endometrial CTC in terms of pathogenesis, hormone receptor pathways, stem cell markers and epithelial to mesenchymal transition (EMT) drivers were asked. Kruskal-Wallis analysis followed by Dunn’s post-test was used for comparisons between groups. Statistical significance was set at p < 0.05. EpCAM-based immunoisolation positively detected CTC in high-risk endometrial cancer patients. CTC characterization indicated a remarkable plasticity phenotype defined by the expression of the EMT markers ETV5, NOTCH1, SNAI1, TGFB1, ZEB1 and ZEB2. In addition, the expression of ALDH and CD44 pointed to an association with stemness, while the expression of CTNNB1, STS, GDF15, RELA, RUNX1, BRAF and PIK3CA suggested potential therapeutic targets. We further recapitulated the EMT phenotype found in endometrial CTC through the up-regulation of ETV5 in an EC cell line, and validated in an animal model of systemic dissemination the propensity of these CTC in the accomplishment of metastasis. Our results associate the presence of CTC with high-risk EC. Gene-expression profiling characterized a CTC-plasticity phenotype with stemness and EMT features. We finally recapitulated this CTC-phenotype by over-expressing ETV5 in the EC cell line Hec1A and demonstrated an advantage in the promotion of metastasis in an in vivo mouse model of CTC dissemination and homing.
Hypoxia/Reoxygenation Stimulates Jun Kinase Activity Through Redox Signaling in Cardiac Myocytes
Authors: Keith R. Laderoute, Keith A. Webster
Journal: Circulation Research (1997)

Hypoxia and reoxygenation are principal components of myocardial ischemia and reperfusion and have distinctive effects on the tissue. Both conditions have been associated with inflammation, necrosis, apoptosis, and myocardial infarction. Using a cell culture model of ischemia and reperfusion in which cardiac myocytes were exposed to cycles of hypoxia and reoxygenation, we report here that reoxygenation, but not hypoxia alone, caused sustained approximately 10-fold increases in phosphorylation of the amino-terminal domain of the c-jun transcription factor. The activation was similar to treatments with anisomycin or okadaic acid and correlated with the hypoxia-mediated depression of intracellular glutathione. Reoxygenation-induced c-Jun kinase activity was reduced by preincubating myocytes during the hypoxia phase with the spin-trap agent alpha-phenyl N-tert-butylnitrone or with N-acetylcysteine. The kinase activation was also inhibited by the tyrosine kinase inhibitor genistein but not by other protein kinase inhibitors. These results implicate unquenched reactive oxygen intermediates as the stimulus that initiates a kinase pathway involving the stress-activated protein kinases (JNKs/SAPKs) in reoxygenated cardiac myocytes.
Treatment of intestinal Behcet's syndrome with chimeric tumour necrosis factor alpha antibody
Authors: S P L Travis
Journal: Gut (2001)

Few patients with Behçet's syndrome have gastrointestinal ulceration. Such patients are difficult to treat and have a higher mortality. Faced with refractory symptoms in two patients with intestinal Behçet's, we used the tumour necrosis factor alpha (TNF-alpha) monoclonal antibody infliximab to induce remission. Both women (one aged 27 years, the other 30 years) presented with orogenital ulceration, pustular rash, abdominal pain, bloody diarrhoea due to colonic ulceration, weight loss, and synovitis. One had thrombophlebitis, digital vasculitis, perianal fistula, and paracolic abscess; the other had conjunctivitis and an ulcer in the natal cleft. Treatment with prednisolone, methyl prednisolone, and thalidomide in one and prednisolone, colchicine, and cyclosporin in the other was ineffective. After full discussion, infliximab (3 mg/kg, dose reduced because of recent sepsis in one, and 5 mg/kg in the other) was administered. Within 10 days the ulcers healed, with resolution of bloody diarrhoea and all extraintestinal manifestations. A second infusion of infliximab was necessary eight weeks later in one case, followed by sustained (>15 months) remission on low dose thalidomide. Remission was initially sustained for 12 months in the other but thalidomide had to be stopped due to intolerance, and a good response to retreatment lasted only 12 weeks without immunosuppression, before a third infusion. The cause of Behçet's syndrome is unknown but peripheral blood CD45 gammadelta T cells in Behçet's produce >50-fold more TNF-alpha than controls when stimulated with phorbol myristate acetate and anti-CD3. Infliximab could have a role for inducing remission in Behçet's syndrome.
Tissue Plasminogen Activator, von Willebrand Factor, and Risk of Type 2 Diabetes in Older Men
Authors: S. Goya Wannamethee, Naveed Sattar, Ann Rumley, Peter H. Whincup, Lucy Lennon, Gordon D.O. Lowe
Journal: Diabetes Care (2008)

OBJECTIVE—The objective of this study was to assess the relationship between putative markers of endothelial dysfunction (tissue plasminogen activator [t-PA] antigen and von Willebrand factor [vWF] antigen) and development of type 2 diabetes, as well as the role of inflammation, adipokines, hepatic function, and insulin resistance in modifying these relationships. RESEARCH DESIGN AND METHODS—This was a prospective study of 3,562 nondiabetic men aged 60–79 years followed up for an average of 7 years during which there were 162 incident cases of type 2 diabetes. RESULTS—Elevated t-PA (top third) was associated with a near threefold increase in risk of diabetes compared with the risk in those in the bottom third after adjustment for lifestyle factors and waist circumference (relative risk [RR] 2.98 [95%CI 1.79–5.00]; Ptrend &amp;lt; 0.0001); weaker but significant (marginal) associations were seen with vWF (1.24 [0.83–1.85]; P = 0.05 for trend). Both biomarkers of endothelial dysfunction correlated significantly with markers of inflammation (interleukin-6 [IL-6] and C-reactive protein [CRP]), hepatic function (γ-glutamyl transferase [GGT]), and insulin resistance, with t-PA showing stronger associations with adiposity, hepatic function, and insulin resistance than vWF. t-PA was also significantly and inversely associated with adiponectin. Adjustment for IL-6, adiponectin, and GGT attenuated the association of incident diabetes with vWF (1.06 [0.71–1.60]), but the relationship seen with t-PA remained significant (adjusted RR 2.19 [1.29–3.70]). Subsequent adjustment for insulin attenuated the association further, but t-PA was still associated with a significant increase in risk (1.66 [0.96–2.85]; Ptrend = 0.02). CONCLUSION—t-PA antigen, but not vWF antigen, is independently associated with risk of type 2 diabetes.
<i>CD14</i> and Toll-like Receptor Gene Polymorphisms, Country Living, and Asthma in Adults
Authors: Lidwien A. M. Smit, Valérie Siroux, Emmanuelle Bouzigon, Marie-Pierre Oryszczyn, Mark Lathrop, Florence Demenais, Francine Kauffmann
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

It has been shown that country living protects against asthma, which may be explained by microbial exposures.To study whether single nucleotide polymorphisms (SNPs) in CD14 and Toll-like receptor (TLR) 2, TLR4 and TLR9 genes are associated with asthma in adults, and whether these SNPs modify associations between country living and asthma.Twenty-five SNPs in CD14, TLR2, TLR4, and TLR9 genes were genotyped in adult subjects from the French Epidemiological study on the Genetics and Environment of Asthma, Bronchial Hyperresponsiveness, and Atopy (EGEA). We conducted a case-control analysis on unrelated subjects (239 with asthma and 596 without asthma), and a family-based association test (FBAT) in 192 families ascertained through probands with asthma.The TLR2/+596 C allele was associated with an increased risk for asthma in both case-control and family-based analyses (under a dominant model, odds ratio [OR] 1.91 and 95% confidence interval [CI] 1.34-2.72, P = 0.0003; Z statistics from FBAT = 2.48, P = 0.01). In skin prick test (SPT) positive subjects, the CD14/-260 C allele was negatively associated with asthma (additive model, OR 0.66; CI 0.48-0.91). Significant gene-environment interactions between variation in CD14 and TLR genes and country living during childhood were found for ten SNPs. In SPT positive subjects carrying CD14/-260 CC, country living protected against asthma (OR, 0.32; 95% CI, 0.12-0.85), whereas country living was not associated with asthma in subjects who were atopic and carrying CD14/-260 T (OR, 1.11; 95% CI, 0.65-1.90) (gene-environment interaction, P < 0.05).TLR2 and CD14 SNPs were associated with asthma and atopic asthma respectively. In addition, CD14, TLR2, TLR4, and TLR9 SNPs modified associations between country living and asthma.
Reconstructed heterograft aortic valves for human use: Preparation and surgical implantation for mitral, aortic, and tricuspid replacement
Authors: M. I. Ionescu, Y. A. S. Mashhour, G. H. Wooler
Journal: Thorax (1968)

The technique of preparing prosthetic aortic heterologous valves for clinical use is outlined in detail, and the surgical implantation of these grafts into the mitral, aortic, and tricuspid areas is described. Between February and December 1967, 42 such grafts have been inserted into 41 patients with good results up to 10 months since the operation. No systemic emboli have occurred although anticoagulants have not been used for more than four to six weeks postoperatively.
Muscle dysmorphia in weightlifters
Authors: B Chung
Journal: British Journal of Sports Medicine (2003)

I would like to raise a concern with regard to the article “Muscle dysmorphia: a new syndrome in weightlifters” by Choi et al .1 Although chronic obsessive behaviour related to fitness and weightlifting is genuinely a concern for both sexes, Choi et al fail, in my opinion, to present a valid argument for the construction of “muscle dysmorphia” as being a separate and distinct subcategory of body dysmorphic disorder. Inclusion …
Renal ammoniagenesis in an early stage of metabolic acidosis in man.
Authors: A Tizianello, G Deferrari, G Garibotto, C Robaudo, N Acquarone, G M Ghiggeri
Journal: Journal of Clinical Investigation (1982)

Total renal ammonia production and ammonia precursor utilization were evaluated in patients under normal acid-base balance and in patients with 24-h NH4Cl acidosis by measuring (a) ammonia excreted with urine and that added to renal venous blood, and (b) amino acid exchange across the kidney. In 24-h acidosis not only urinary ammonia excretion is increased, but also total ammonia production is augmented (P less than 0.005) in comparison with controls. By evaluating the individual role of acid-base parameters, urine pH and urine flow in influencing renal ammonia production, it was shown that the degree of acidosis and urine flow are likely major factors stimulating ammoniagenesis. Both urine pH and urine flow are determinant in the preferential shift of ammonia into urine. In 1-d acidosis, renal extraction of glutamine was not increased and the total ammonia produced/glutamine N extracted ratio was higher than in controls (P less than 0.005) and was inversely correlated with the log of arterial bicarbonate concentration (P less than 0.001). In the same condition, renal glycine and ornithine uptake took place; the more severe the acidosis, the greater was the renal extraction of these amino acids (P less than 0.001). These data indicate that at the early stages of metabolic acidosis, in spite of a brisk increase in ammonia production, the mechanisms responsible for the increased glutamine use, which are operative in chronic acidosis, are not activated and other ammonia precursors, besides glutamine, are probably used for ammonia production.
Affective spectra, synchronization, and motion: Aspects of the emotional response to music
Authors: Jamshed J. Bharucha, Meagan Curtis
Journal: Behavioral and Brain Sciences (2008)

Abstract We propose three extensions of the theory developed by Juslin &amp; Västfjäll (J&amp;V). First, motion should be considered as an additional mechanism. Second, synchronization plays a role in eliciting emotion. And, third, the spectrum of musical affect or feelings is denser and broader than the spectrum of emotions, suggesting an expansion of the scope of the theory beyond emotions.
Gene therapy for lung inflammatory diseases: not so far away?
Authors: J. M. Sallenave, D. J. Porteous, C. Haslett
Journal: Thorax (1997)

The lung is a readily accessible target organ for gene therapy. To date, therapeutic gene delivery has largely focused on introducing functional, corrective genes in lung diseases arising from single gene defects such as cystic fibrosis. More recently interest has centred on gene therapy as a potential therapeutic tool in modulating complex pathological processes such as pulmonary inflammation. Genetic modification of critical components of the inflammatory process may be beneficial-for example, overexpressing anti-elastase genes may circumvent elastase mediated lung damage in emphysema. With the development of improved viral and liposome vectors and the evolution of effective adjuvant immunosuppression to obviate host immune responses--for example, using selective cytokines and blockers of T cell surface activation--the potential exists to target therapeutic doses of transgene to deficient or dysregulated cells. Furthermore, increased understanding of tissue-specific promoter regions and of mechanisms controlling regulation of gene expression offer the potential for close control of therapeutic gene expression within the lung. Continuing refinements in these technologies will provide new therapeutic strategies in inflammatory lung disease.
PRICE needs updating, should we call the POLICE?
Authors: C M Bleakley, P Glasgow, D C MacAuley
Journal: British Journal of Sports Medicine (2011)

220 The acronym PRICE (protection, rest, ice, compression and elevation) has been central to acute soft tissue injury management for many years despite a paucity of high-quality, empirical evidence to support the various components or as a collective treatment package. Treatment paradigms in sports medicine must be updated based on contemporary research evidence. As a recent example, the widespread use of non-steroidal antiinfl ammatory drugs in acute soft tissue injury management has been challenged, particularly with ligament and muscle injuries. 1 Ice compression and elevation (ICE) is the basic principle of early treatment. Most research has focused on the analgesic effect of icing or the associated skin or intramuscular temperature changes; a recent randomised controlled trial by Prins and colleagues, 2 which examined the effectiveness of ice on recovery from acute muscle tear, is the fi rst of its kind. Clinical studies into compression are also lacking, and much of its rationale is extrapolated from research relating to deep venous thrombosis prophylaxis and lymphoedema management; there is little clinical research on elevation. 3
Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease
Authors: Laura M. Paulin, Gregory B. Diette, Paul D. Blanc, Nirupama Putcha, Mark D. Eisner, Richard E. Kanner, Andrew J. Belli, Stephanie Christenson, Donald P. Tashkin, MeiLan Han, R. Graham Barr, Nadia N. Hansel
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear.Objectives: To determine the impact of occupational exposures on COPD morbidity.Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George's Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years.Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03).Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may influence disease burden.
Mechanisms of clearance of nontypeable Haemophilus influenzae from cigarette smoke-exposed mouse lungs
Authors: G.J. Gaschler, C.C.J. Zavitz, C.M.T. Bauer, M.R. Stämpfli
Journal: European Respiratory Journal (2010)

Inflammation is prevalent in all stages of chronic obstructive pulmonary disease, and, furthermore, individuals undergo periods of exacerbation, during which pulmonary inflammation increases, often a result of bacterial infection. The present study investigates the in vivo consequences of cigarette smoke exposure on bacterial challenge with nontypeable Haemophilus influenzae (NTHi). BALB/c and C57 black 6 (C57BL/6) mice were exposed to cigarette smoke once or twice daily for a total period of 8 weeks. Exacerbated inflammation was observed in cigarette smoke-exposed compared to room-air-exposed mice following challenge with live or heat-inactivated NTHi. Accelerated clearance of live NTHi from cigarette smoke-exposed mice was independent of the establishment of chronic inflammation or direct toxic effects of cigarette smoke components on bacteria. Mechanistically, a cell-free factor in the bronchoalveolar lavage fluid contributed to accelerated clearance following passive transfer to naive mice. Further investigation demonstrated increased titres of immunoglobulin A in the bronchoalveolar lavage fluid, but not the blood, of cigarette smoke-exposed mice, including increased titres of NTHi-specific immunoglobulin A, whereas heavy chain joining element (J H ) -/- B-cell-deficient cigarette smoke-exposed mice did not demonstrate decreased bacterial burden following challenge. The present results demonstrate that cigarette smoke exposure results in exacerbated inflammation following challenge with NTHi, as well as increased titres of antibodies that contribute to bacterial clearance.
Selective depletion of a minor subpopulation of B-chronic lymphocytic leukemia cells is followed by a delayed but progressive loss of bulk tumor cells and disease regression
Authors: Aaron E Foster, Fatma V Okur, Ettore Biagi, An Lu, Gianpietro Dotti, Eric Yvon, Barbara Savoldo, George Carrum, Michael Andreeff, Margaret A Goodell, Helen E Heslop, Malcolm K Brenner
Journal: Molecular Cancer (2009)

Cancer precursor/progenitor cells may initiate and sustain the growth of tumors, but evidence for their existence in human disease is indirect, relying on their in vitro properties and animal models. More directly, specific elimination of these rare cells from cancer patients should produce a delayed but progressive disappearance of differentiated malignant progeny. Here, we describe selective eradication of a putative precursor population in a patient with B-cell chronic lymphocytic leukemia, followed 6 months later by a progressive loss of mature tumor cells without further treatment. This outcome supports the presence of a rare population of precursor/progenitor cells in human malignancies, and suggests benefit from their removal.