tbuckley/cabot-search huggingface dataset:
CD4+Foxp3+ regulatory T cell expansion induced by antigen-driven interaction with intestinal epithelial cells independent of local dendritic cells
Authors: A M Westendorf, D Fleissner, L Groebe, S Jung, A D Gruber, W Hansen, J Buer
Journal: Gut (2008)

<h3>Background:</h3> Regulatory T cells (T<sub>regs</sub>) have potential anti-inflammatory effects and are likely to be important in the pathogenesis of chronic inflammatory bowel disease (IBD). However, the induction and expansion of T<sub>regs</sub> at sites of mucosal inflammation are not yet fully understood and may involve antigen presentation by local dendritic cells (DCs) and/or intestinal epithelial cells (IECs). <h3>Methods:</h3> To determine the unique ways in which the gut induces or expands T<sub>regs</sub>, a transgenic mouse model that is based on the specific expression of a model autoantigen (influenza haemagglutinin (HA)) in the intestinal epithelium (VILLIN-HA) was used. Gut-associated DCs and IECs isolated from these mice were phenotypically and functionally characterised for the potential to interact with HA-specific T<sub>regs</sub> in vitro and in vivo. <h3>Results:</h3> Intestinal self-antigen expression leads to peripheral expansion of antigen-specific CD4<sup>+</sup>Foxp3<sup>+</sup> T<sub>regs</sub>. Although gut-associated DCs can induce antigen-specific CD4<sup>+</sup>Foxp3<sup>+</sup> T cell proliferation, in vivo depletion of DCs did not preclude proliferation of these cells. Interestingly, antigen presentation by primary IECs is sufficient to expand antigen-specific CD4<sup>+</sup>Foxp3<sup>+</sup> T<sub>regs</sub> efficiently. This is dependent on major histocompatibility complex class II, but, in contrast to DCs, is unlikely to require transforming growth factor β and retinoic acid. <h3>Conclusion:</h3> This study provides experimental evidence for a new concept in mucosal immunity: in contrast to current thinking, expansion of T<sub>regs</sub> can be achieved independently of local DCs through antigen-specific IEC–T cell interactions.
Chromosomes, Hypoxia, Angiogenesis, and Trial Design: A Brief History of Renal Cancer Drug Development
Authors: Walter Stadler
Journal: Clinical Cancer Research (2007)

The recent development of effective therapy for renal cancer is a fascinating story of successful translational research that encompasses fundamental studies of oncogenesis and hypoxia, preclinical investigations of antiangiogenic therapy, and the use of novel clinical trial designs. In fact, no
Randomized Phase II Trial of Gemcitabine Plus TH-302 Versus Gemcitabine in Patients With Advanced Pancreatic Cancer
Authors: Mitesh J. Borad, Shantan G. Reddy, Nathan Bahary, Hope E. Uronis, Darren Sigal, Allen L. Cohn, William R. Schelman, Joe Stephenson, E. Gabriela Chiorean, Peter J. Rosen, Brian Ulrich, Tomislav Dragovich, Salvatore A. Del Prete, Mark Rarick, Clarence Eng, Stew Kroll, David P. Ryan
Journal: Journal of Clinical Oncology (2014)

TH-302 is an investigational hypoxia-activated prodrug that releases the DNA alkylator bromo-isophosphoramide mustard in hypoxic settings. This phase II study (NCT01144455) evaluated gemcitabine plus TH-302 in patients with previously untreated, locally advanced or metastatic pancreatic cancer.
High-Dose Melphalan With Autologous Stem-Cell Rescue in Metastatic Rhabdomyosarcoma
Authors: M. Carli, R. Colombatti, O. Oberlin, M. Stevens, L. Masiero, E. Frascella, E. Koscielniak, J. Treuner, C. R. Pinkerton
Journal: Journal of Clinical Oncology (1999)

PURPOSE: The European Collaborative MMT4-91 trial was conducted as a prospective nonrandomized study to evaluate the potential benefit of high-dose melphalan as consolidation of first complete remission in children with stage IV rhabdomyosarcoma. PATIENTS AND METHODS: Fifty-two patients in complete remission after six courses of chemotherapy received “megatherapy”: 42 received melphalan alone, whereas 10 received melphalan in combination with etoposide, carboplatin/etoposide, or thiotepa/busulfan and etoposide. The outcome of this group of patients was compared with that observed in 44 patients who were also in complete remission after six courses of identical chemotherapy (plus surgery or radiotherapy) but went on to receive a total of up to 12 courses of conventional chemotherapy (four cycles). No differences were found between the two groups regarding clinical characteristics, chemotherapy received before complete remission, or response to chemotherapy. In particular, there was no significant difference between the groups for site of primary tumor, histologic subtype, age at presentation, presence of bone or bone marrow metastases, or number of metastases. RESULTS: The 3-year event-free survival (EFS) and overall survival (OS) rates were 29.7% and 40%, respectively, for those receiving high-dose melphalan or other multiagent high-dose regimens and 19.2% and 27.7%, respectively, for those receiving standard chemotherapy. The difference was not statistically significant (P = .3 and P = .2 for EFS and OS, respectively). There was a significant prolongation in the time from the last day of high-dose chemotherapy or the end of chemotherapy cycle 4 to the time of relapse in those receiving megatherapy (168 days for patients receiving megatherapy v 104 days for those receiving standard therapy; P = .05). CONCLUSION: The addition of a high-dose alkylating agent to consolidation therapy may have prolonged progression-free survival in this poor-risk patient group, but it did not significantly improve the ultimate outcome.
DNA:Anti-DNA Complexes: Their Detection in Systemic Lupus Erythematosus Sera
Authors: Ronald J. Harbeck, Emil J. Bardana, Peter F. Kohler, Ronald I. Carr
Journal: Journal of Clinical Investigation (1973)

Antibody to DNA was measured before and after treatment of systemic lupus erythematosus (SLE) sera with bovine pancreatic deoxyribonuclease (DNase I). In 11 of 15 cases of SLE with active renal disease there was a significant increase in DNA-binding after DNase digestion, while no such increase was noted in inactive SLE, normal controls or in patients with nonlupus renal disease. The significant rise in DNA-binding after digestion indicated that DNA had bound in vivo to the anti-DNA in these sera. A striking correlation between the occurrence of these complexes and disease activity was shown. In eight cases of SLE nephritis where serial blood samples were obtained, the greatest increase in DNA-binding after DNase digestion occurred at the time of the severest renal disease. In addition, serum from a case of SLE with acute cerebritis but without evidence of renal disease also had a significant rise in binding during the acute phase. This assay provides proof of the existence of circulating DNA:anti-DNA complexes in some cases of SLE and can also be used to measure an apparently critical parameter of disease activity.
A Danger of Peptic Ulceration
Authors: P. A. L. Roberts
Journal: BMJ (1954)

In the last seven years eight patients have been observed whose convalescence from surgery and trauma had been interrupted by the appearance or the recrudescence of peptic ulceration.Of these eight patients five died, four as a direct result of their ulcers.It is therefore a complication to be feared, whether the preceding trauma be strictly causal or not.A connexion between trauma and ulceration has long been known, and has been recorded in the literature.Curling (1842), inspired by the observations of Cooper (1839) and Long (1840), collected 11 cases of ulceration following burns, four of which he had treated in per- son in the wards of St. George's Hospital.Billroth (1867) first reported ulceration following operation, citing a case of death from gastro-intestinal haemorrhage on the sixth day after an operation to decom- press a large retrosternal goitre.Von Eiselsberg (1899)described eight cases of ulceration, five fatal, mainly after operations for strangulated hernia.Busse (1905) and von Winiwarter (1911), from the same clinic, developed the theme; the latter collected 30 cases of gastro-intestinal haemorrhage after operations other than on the bowel, 17 of which were fatal.Cushing (1932) described ulceration and necrotic mucosal lesions following intracranial operations and disease.He believed these to be due directly to lesions in the hypothalamus, and he instigated animal experi- ments, such as those of Hoff and Sheehan (1935), to corroborate this belief.Penner and Bernheim (1939), in their study of the pathological changes in "shock," disputed Cushing's conclusions, and ascribed the ulcerating lesions to the non-specific stimulus of the shock.Herbut (1945) and McDonnell and McCloskey (1953) investigated the frequency of acute peptic ulcers in necropsies on patients dying within two months of operation, and found an incidence greater than could be explained by chance.There have been sporadic reports of cases following trauma, such as those by Griffiths (1922), Ramond and Chene (1932), and Gray (1945).There can be little
Penetration of the blood-brain barrier: enhancement of drug delivery and imaging by bacterial glycopeptides.
Authors: B Spellerberg, S Prasad, C Cabellos, M Burroughs, P Cahill, E Tuomanen
Journal: The Journal of Experimental Medicine (1995)

The blood-brain barrier restricts the passage of many pharmacological agents into the brain parenchyma. Bacterial glycopeptides induce enhanced blood-brain barrier permeability when they are present in the subarachnoid space during meningitis. By presenting such glycopeptides intravenously, blood-brain barrier permeability in rabbits was enhanced in a reversible time- and dose-dependent manner to agents &amp;lt; or = 20 kD in size. Therapeutic application of this bioactivity was evident as enhanced penetration of the antibiotic penicillin and the magnetic resonance imaging contrast agent gadolinium-diethylene-triamine-pentaacetic acid into the brain parenchyma.
Z α<sub>1</sub>-Antitrypsin Confers a Proinflammatory Phenotype That Contributes to Chronic Obstructive Pulmonary Disease
Authors: Samuel Alam, Zhenjun Li, Carl Atkinson, Danny Jonigk, Sabina Janciauskiene, Ravi Mahadeva
Journal: American Journal of Respiratory and Critical Care Medicine (2014)

Rationale: Severe α1-antitrypsin deficiency caused by the Z variant (Glu342Lys; ZZ-AT) is a well-known genetic cause for emphysema. Although severe lack of antiproteinase protection is the critical etiologic factor for ZZ-AT–associated chronic obstructive pulmonary disease (COPD), some reports have suggested enhanced lung inflammation as a factor in ZZ-AT homozygotes.Objectives: To provide molecular characterization of inflammation in ZZ-AT.Methods: Inflammatory cell and cytokine profile (nuclear factor-κB, IL-6, tumor necrosis factor-α), intracellular polymerization of Z-AT, and endoplasmic reticulum (ER) stress markers (protein kinase RNA–like ER kinase, activator transcription factor 4) were assessed in transgenic mice and transfected cells in response to cigarette smoke, and in explanted lungs from ZZ and MM individuals with severe COPD.Measurements and Main Results: Compared with M-AT, transgenic Z-AT mice lungs exposed to cigarette smoke had higher levels of pulmonary cytokines, neutrophils, and macrophages and an exaggerated ER stress. Similarly, the ER overload response was greater in lungs from ZZ-AT homozygotes with COPD, and was particularly found in pulmonary epithelial cells. Cigarette smoke increased intracellular Z-AT polymers, ER overload response, and proinflammatory cytokine release in Z-AT–expressing pulmonary epithelial cells, which could be prevented with an inhibitor of polymerization, an antioxidant, and an inhibitor of protein kinase RNA–like ER kinase.Conclusions: We show here that aggregation of intracellular mutant Z-AT invokes a specific deleterious cellular inflammatory phenotype in COPD. Oxidant-induced intracellular polymerization of Z-AT in epithelial cells causes ER stress, and promotes excess cytokine and cellular inflammation. This pathway is likely to contribute to the development of COPD in ZZ-AT homozygotes, and therefore merits further investigation.
Prospective evaluation of the risk of bacteremia associated with transesophageal echocardiography.
Authors: J M Steckelberg, B K Khandheria, J P Anhalt, D J Ballard, J B Seward, R L Click, W R Wilson
Journal: Circulation (1991)

BACKGROUND Transient bacteremia may lead to endocarditis in patients with significant valvular lesions. METHODS AND RESULTS Because transesophageal echocardiography selects a patient population with a high prevalence of valvular lesions, we prospectively evaluated the risk of transient bacteremia associated with transesophageal echocardiography in 49 patients. Blood cultures were obtained immediately before transesophageal echocardiography and at 5, 10, and 20 minutes after the start of the procedure. For each culture, 30 ml venous blood was obtained and 10 ml was inoculated into each of an Isolator tube, Septi-chek bottle, and a nonvented Trypticase soy broth bottle. Broth cultures were incubated for 14 days. Blood from the Isolator tube was plated onto appropriate media for recovery of bacteria and fungi. Two patients were excluded from analysis because the final two sets of blood cultures could not be obtained. Among the remaining 47 study patients, two preprocedure control blood cultures were positive, and two of 141 subsequent cultures were positive. All isolates were considered contaminants. Thus, we found no significant bacteremia due to pathogenic oral flora during transesophageal echocardiography (0%; 95% CI, 0.0-7.5%). CONCLUSIONS Although recommendations for antimicrobial prophylaxis for transesophageal echocardiography should be individualized for each patient, many patients may not require antimicrobial prophylaxis.
Prenatal Exposure to Maternal Genital and Reproductive Infections and Adult Schizophrenia
Authors: Vicki Babulas, Pam Factor-Litvak, Raymond Goetz, Catherine A Schaefer, Alan S Brown
Journal: American Journal of Psychiatry (2006)

Objective: In this birth cohort study, the authors examined the relation between prenatal exposure to maternal genital/reproductive (G/R) infections and schizophrenia in offspring. Method: The birth cohort consisted of 7,794 offspring of pregnancies with prospectively acquired data on maternal G/R infections from obstetric records. The authors diagnosed 71 cases of schizophrenia and other schizophrenia spectrum disorders in this cohort. The relationship between maternal G/R infections and schizophrenia risk was modeled. Results: Exposure to G/R infections during the periconceptional period was associated with a significantly increased risk of schizophrenia and other schizophrenia spectrum disorders, with adjustment for maternal race, education, age, and mental illness. Conclusions: Maternal G/R infection during periconception appears to increase the risk of schizophrenia in offspring.
Manipulating myocyte cell cycle control for cardiac repair
Authors: T. A. Gorr, A. Deten
Journal: Cardiovascular Research (2008)

A fundamental tenet in cardiac biology, namely that the heart is a postmitotic organ incapable of regeneration, has recently been challenged. According to the traditional belief, the number of cardiac myocytes we are born with is all we will have for the rest of our lives. If myocytes die (e.g. as the result of infarction), they cannot be renewed. This is why myocardial infarction (MI) and its consequences, such as congestive heart failure, continue to be a major cause of death worldwide despite the considerable therapeutic advances that have been made over the past decades.

In one attempt to evade this dilemma, cell replacement strategies are currently being investigated for their therapeutic potential to restore cardiac function. Indeed, a growing body of evidence from both basic animal studies and clinical trials indicates that cell-based strategies using different stem cell populations such as embryonic stem cells, skeletal myoblasts, haematopoietic stem cells, endothelial progenitor cells, and mesenchymal stem cells might be promising.1,2 According to these studies, improvements in clinical symptoms, left-ventricular function, and myocardial perfusion are feasible with cell therapy. However, there is an ongoing controversy about the underlying mechanisms and, particularly, the capability of the different implanted progenitor cells to transdifferentiate and what the essential prerequisites for this transdifferentiation might be. Only on understanding these mechanisms and, likely, through the appropriate priming and engineering of the cells to be implanted regeneration by this approach might be achieved.

Another approach to induce cardiac regeneration for repair after injury would be to reverse the terminal differentiation, as many mammalian tissues respond to injury by activating … 

*Corresponding author. Tel: +49 341 972 5810; fax: +49 341 972 5809. E-mail address: alexander.deten{at}izi.fraunhofer.de
Early effect of aldosterone on the rate of synthesis of the epithelial sodium channel alpha subunit in A6 renal cells.
Authors: A May, A Puoti, H P Gaeggeler, J D Horisberger, B C Rossier
Journal: Journal of the American Society of Nephrology (1997)

Transepithelial Na+ reabsorption across tight epithelia is regulated by aldosterone. The amiloride-sensitive epithelial sodium channel (ENaC) is a major target for the natriferic action of aldosterone. In this study, the effect of aldosterone on ENaC mRNA abundance and the rate of protein synthesis for each of the three ENaC subunits (alpha, beta and gamma) in the A6 kidney cell line were examined. In cells grown on plastic, aldosterone induced a large and rapid increase in epithelial sodium channel (ENaC) beta and gamma subunit mRNA abundance, but this effect is not translated into the synthesis of the corresponding proteins. In cells grown on a porous substrate, amiloride-sensitive electrogenic sodium transport was expressed and was upregulated by aldosterone (300 nM) as early as 1 h after the addition of the hormone. The alpha, beta, and gamma mRNA abundance was not changed by aldosterone during the first 3 h of stimulation, whereas a fourfold increase over control was observed after 24 h. The rate of synthesis of alpha subunit was significantly increased above control already 60 min after aldosterone addition, whereas beta subunit synthesis increased only 6 h after hormone addition, with no significant change for the gamma subunit. The half-lives of each subunit as assessed by 35S methionine pulse-chase experiments were short (between 40 and 50 min) and were not modified by aldosterone. Taking into account the short half-life of ENaC protein and assuming that the synthesis of the alpha subunit is a limiting factor in the assembly and expression of new channels at the cell surface, it is proposed that the aldosterone regulation of sodium transport might be, in part, mediated by de novo synthesis of the channel protein.
Angiotensin-converting enzyme genotype and C-reactive protein in patients with COPD
Authors: R. Tkacova, P. Joppa
Journal: European Respiratory Journal (2007)

To the Editors: 

In a recent issue of the European Respiratory Journal , Meysman 1 suggested that in studies on the effects of angiotensin-converting enzyme (ACE) blockers in patients with chronic obstructive pulmonary disease (COPD), stratification for ACE gene polymorphism could potentially affect the outcomes under investigation. We have shown previously that the insertion (I)/deletion (D) polymorphism at intron 16 of the ACE gene is linked to pulmonary artery pressure ( P pa) in patients with COPD 2. In addition, in our recent study, increases in P pa were associated with higher serum levels of high-sensitivity C-reactive protein (hsCRP), raising the possibility of a pathogenetic role of low-grade systemic inflammation in the pathogenesis …
Quantitative In Vivo Studies of Soluble Simian Virus 40 Tumor-Specific Transplantation Antigens of the Mouse
Authors: O. Henriksen, L. W. Law, E. Appella
Journal: JNCI Journal of the National Cancer Institute (1977)

Journal Article Quantitative In Vivo Studies of Soluble Simian Virus 40 Tumor-Specific Transplantation Antigens of the Mouse Get access O. Henriksen, O. Henriksen Search for other works by this author on: Oxford Academic PubMed Google Scholar L. W. Law, L. W. Law Search for other works by this author on: Oxford Academic PubMed Google Scholar E. Appella E. Appella Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 58, Issue 6, June 1977, Pages 1785–1788, https://doi.org/10.1093/jnci/58.6.1785 Published: 01 June 1977 Article history Received: 01 September 1976 Accepted: 07 December 1976 Published: 01 June 1977
Tobacco use and secondhand smoke exposure levels among Muslim community in Ireland
Authors: Zubair Kabir, Sheila Keogan, Vanessa Clarke, Luke Clancy
Journal: European Respiratory Journal (2013)

Background and objectives   Smoking among ethnic minorities and immigrants continues to be a tobacco control policy issue in many industrialized nations. Ireland experienced recent immigration. We characterized tobacco use and secondhand smoke (SHS) levels among the Muslim community in Ireland considering the recent heterogeneous nature of the Irish population.   Methods   A validated questionnaire, with additional questions tailored to the Muslim community, was administered between July 2011 and January 2012, online (survey-monkey link, in English) and a self-administered print questionnaire survey (in Bengali, English and Arabic). The survey was distributed through a Muslim magazine and emailed to well-known Irish Muslim organizations. 270 online and 130 print questionnaire responses (field interviewer-administered) totalling 400 respondents were collected.  Both descriptive and chi-square tests of proportions were performed using SPSS (v 18.0).   Results   Age-adjusted current tobacco users was 21.9% (28% men and 10% women); 4.3% consumed smokeless products. 27% in 26-45 years of age were current tobacco users; surprisingly 25% in higher educated individuals used tobacco compared to 18% with lower levels of education. 25.3% are former tobacco users. 14.3% of the recent migrants (   Conclusion   Muslim men in Ireland from many different nations have smoking rates similar to Irish men, Muslin women smoke less than Irish women. SHS exposure was high.