tbuckley/cabot-search huggingface dataset:
Supplementation with vitamin A early in life and subsequent risk of asthma
Authors: W. Checkley, K.P. West, R.A. Wise, L. Wu, S.C. LeClerq, S. Khatry, J. Katz, P. Christian, J.M. Tielsch, A. Sommer
Journal: European Respiratory Journal (2011)

Animal models suggest that vitamin A deficiency affects lung development adversely and promotes airway hyperresponsiveness, and may predispose to an increased risk of asthma. We examined the long-term effects of vitamin A supplementation early in life on later asthma risk. In 2006–2008, we revisited participants from two cohorts in rural Nepal who were enrolled in randomised trials of vitamin A supplementation. The first cohort received vitamin A or placebo for &lt;16 months during their pre-school years (1989–1991). The second cohort was born to mothers who received vitamin A, β-carotene or placebo before, during and after pregnancy (1994–1997). At follow-up, we asked about asthma symptoms and performed spirometry. Out of 6,421 subjects eligible to participate, 5,430 (85%) responded to our respiratory survey. Wheezing prevalence during the previous year was 4.8% in participants aged 9–13 yrs and 6.6% in participants aged 14–23 yrs. We found no differences between the vitamin A supplemented and placebo groups from either trial in the prevalence of lifetime or current asthma and wheeze or in spirometric indices of obstruction (p≥0.12 for all comparisons). Vitamin A supplementation early in life was not associated with a decreased risk of asthma in an area with chronic vitamin A deficiency.
Effects of Pinacidil on Electrophysiological Properties of Epicardial Border Zone of Healing Canine Infarcts
Authors: James Coromilas, Constantinos Costeas, Bernard Deruyter, Stephen M. Dillon, Nicholas S. Peters, Andrew L. Wit
Journal: Circulation (2002)

Background — K ATP channels, activated by ischemia, participate in the arrhythmogenic response to acute coronary occlusion. The function of these channels in border zones of healing infarcts, where arrhythmias also arise, has not been investigated. Do these channels remain maximally activated during infarct healing, or do they downregulate after a period of time? Both might preclude further activation. Methods and Results — Myocardial infarction was produced in dogs by ligation of the left anterior descending coronary artery. Impulse propagation in the epicardial border zone (EBZ) of 4-day-old healing infarcts was mapped during administration of pinacidil, a K ATP channel activator, directly into the EBZ coronary blood supply. Pinacidil restored conduction and excitability when the EBZ was initially inexcitable and had large regions of block (6 of 8 experiments). This allowed reentrant circuits to form in the EBZ, causing tachycardia (4 of 8 experiments ) . In hearts with an initially excitable EBZ, pinacidil shortened the effective refractory period and abolished conduction block at short cycle lengths (7 experiments). This effect prevented initiation of reentry (1 of 2 experiments). Conclusions — The response to pinacidil indicates that K ATP channels in the EBZ remain functional and can be activated to influence electrophysiological properties and arrhythmogenesis.
Enhanced Release of Superoxide from Polymorphonuclear Neutrophils in Obstructive Sleep Apnea
Authors: RICHARD SCHULZ, SIAMAK MAHMOUDI, KATJA HATTAR, ULF SIBELIUS, HORST OLSCHEWSKI, KONSTANTIN MAYER, WERNER SEEGER, FRIEDRICH GRIMMINGER
Journal: American Journal of Respiratory and Critical Care Medicine (2000)

Obstructive sleep apnea (OSA) is associated with increased cardiovascular morbidity and mortality. Free oxygen radicals have been implicated in the pathogenesis of cardiovascular disorders. Therefore, we aimed to test the hypothesis that increased oxidative stress constitutes one underlying mechanism for the connection between OSA and cardiovascular disease. In 18 patients with OSA the release of superoxide from polymorphonuclear neutrophils was determined after stimulation with the bacterial tripeptide formylmethionylleucylphenylalanine (fMLP) and the calcium ionophore A23. Superoxide production was measured as superoxide dismutase-inhibitable reduction of cytochrome c. Blood samples were obtained before and after two nights of CPAP therapy and after 4.8 ± 0.6 mo of follow-up. Ten healthy young volunteers and 10 lung cancer patients without OSA but a similar spectrum of comorbidity served as controls. Before CPAP, neutrophil superoxide generation was markedly enhanced in OSA when compared with both control groups. Effective CPAP therapy led to a rapid and long-lasting decrease of superoxide release in OSA. In conclusion, OSA is linked with a “priming” of neutrophils for enhanced respiratory burst. The increased superoxide generation, which might have major impact on the development of cardiovascular disorders, is virtually fully reversed by effective CPAP therapy.
Low-density lipoprotein receptor activity in cultured human skin fibroblasts. Mechanism of insulin-induced stimulation.
Authors: A Chait, E L Bierman, J J Albers
Journal: Journal of Clinical Investigation (1979)

Low-density lipoproteins (LDL) receptor activity, as reflected by LDL degradation, was stimulated by the addition of insulin to cultures of human skin fibroblasts. These changes occurred independently of the glucose concentration of the incubation medium and occurred whether or not LDL receptor activity was suppressed. A comparison of the saturation kinetics of LDL receptor activity in the presence and absence of insulin indicated that insulin produced a 35% increase in Vmax with no difference in "apparent Km". These results suggest that insulin enhances LDL receptor activity by increasing the number of LDL receptors rather than by influencing binding affinity. In confirmation, LDL degradation by receptor negative cells was not enhanced by insulin. Sterol synthesis from [14C]acetate was also stimulated by insulin, but egress of cholesterol and cellular cholesterol content were unaffected by the hormone. The effect of insulin on LDL receptors was not dependent on its known ability to enhance cellular DNA synthesis and proliferation, because insulin stimulated LDL receptor activity in cells kept quiescent by maintenance in plasma-derived serum that was devoid of platelet derived growth factor. Nevertheless, the effect of insulin in enhancing LDL receptor number, coupled with stimulation of endogenous cholesterol synthesis, provides a mechanism whereby the cell could theoretically increase its supply of cholesterol during times of additional need.
Updated model of group A Streptococcus M proteins based on a comprehensive worldwide study
Authors: D.J. McMillan, P. -A. Drèze, T. Vu, D.E. Bessen, J. Guglielmini, A.C. Steer, J.R. Carapetis, L. Van Melderen, K.S. Sriprakash, P.R. Smeesters
Journal: Clinical Microbiology and Infection (2012)
Low-dose corticosteroids during severe community-acquired pneumonia: end of the story
Authors: Jean-Damien Ricard, Jonathan Messika
Journal: European Respiratory Journal (2015)

Community-acquired pneumonia (CAP) remains a leading cause of death worldwide despite improvement in patient management. Early recognition of lung infection and prompt initiation of adequate antibiotherapy are crucial elements to ensuring favourable outcomes [1–3]. Nonetheless, in a number of cases, death occurs despite both these targets being met. In these patients, possible excessive inflammatory responses, as in sepsis and septic shock, are believed to contribute to unfavourable outcome. Animal models have elegantly shown that part of the inflammatory response, initially destined to combat the pathogens invading the lungs (such as neutrophil products) may induce tissue damage even in the absence of any bacterial challenge [4]. They have also provided evidence that inhibiting inflammatory signalling lessens lung injury in murine models of Escherichia coli [5, 6] or Pseudomonas aeruginosa [7] pneumonia. These results and many others have prompted clinicians to investigate the potential benefit of administering corticosteroids to counterbalance an intense inflammatory process in order to improve outcome. This search has been a long and winding road which many researchers have taken with varying success. In cases of community-acquired pneumonia, corticosteroids should only be given if septic shock is also present <http://ow.ly/FUCHN>
Two-locus involvement in the association of human leukocyte antigen with the extrahepatic manifestations of autoimmune chronic active hepatitis
Authors: Yanina Makcos, Hugo A. Fainboim, Mónica Capucchio, Jorge Findor, Jorge Daruich, Beatriz Reyes, Marcelo Pando, Graciela Del C. Theiler, Nora Méndez, Leonardo M. Satz, Leonardo Fainboim
Journal: Hepatology (1994)

We investigated the association of human leukocyte antigen antigens and type 1 chronic active "autoimmune" hepatitis in a population of 65 white Argentinian patients, taking into account the different manifestations of the disease. Standard microlymphocytotoxicity was used for human leukocyte antigen A, B, C, DR and DQ typing. Human leukocyte antigen class 2 alleles were also typed on genomic DNA by means of polymerase chain reaction amplification and hybridization to sequence specific oligonucleotides. A primary association with human leukocyte antigen DR4 was present (human leukocyte antigen DR4: 44% in patients vs. 29% in controls; chi 2, 5.6; p = 0.02, relative risk, 2.1). However, a novel association was observed with human leukocyte antigen A11 (31% in patients vs. 6% in the controls; chi 2, 25.3; corrected p = 0.001; relative risk, 6.8). Moreover, of the 20 human leukocyte antigen A11 patients, 18 had extrahepatic manifestations associated with autoimmune chronic active hepatitis. This represented 60% of the patients bearing this form of the disease (n = 30), conferring a relative risk of 22.2 (chi 2, 46.3; corrected p = 0.00008). In this group, human leukocyte antigen DR3 and DR4 had a weak association. When present together, human leukocyte antigen DR4 and human leukocyte antigen A11 had a synergistic effect, yielding an odds ratio of 357. Statistical analysis and family segregation studies suggest that the two loci products may represent independent risk factors for this form of autoimmune chronic active hepatitis. This synergistic effect was not evident with A11 plus DR3. In autoimmune chronic active hepatitis patients without extrahepatic manifestations, a weak association with human leukocyte antigen DR6 was found.(ABSTRACT TRUNCATED AT 250 WORDS)
<i>MAX</i> Inactivation in Small Cell Lung Cancer Disrupts MYC–SWI/SNF Programs and Is Synthetic Lethal with BRG1
Authors: Octavio A. Romero, Manuel Torres-Diz, Eva Pros, Suvi Savola, Antonio Gomez, Sebastian Moran, Carmen Saez, Reika Iwakawa, Alberto Villanueva, Luis M. Montuenga, Takashi Kohno, Jun Yokota, Montse Sanchez-Cespedes
Journal: Cancer Discovery (2013)

Our knowledge of small cell lung cancer (SCLC) genetics is still very limited, amplification of L-MYC, N-MYC, and C-MYC being some of the well-established gene alterations. Here, we report our discovery of tumor-specific inactivation of the MYC-associated factor X gene, MAX, in SCLC. MAX inactivation is mutually exclusive with alterations of MYC and BRG1, the latter coding for an ATPase of the switch/sucrose nonfermentable (SWI/SNF) complex. We demonstrate that BRG1 regulates the expression of MAX through direct recruitment to the MAX promoter, and that depletion of BRG1 strongly hinders cell growth, specifically in MAX-deficient cells, heralding a synthetic lethal interaction. Furthermore, MAX requires BRG1 to activate neuroendocrine transcriptional programs and to upregulate MYC targets, such as glycolysis-related genes. Finally, inactivation of the MAX dimerization protein, MGA, was also observed in both non-small cell lung cancer and SCLC. Our results provide evidence that an aberrant SWI/SNF-MYC network is essential for lung cancer development.
Coronary bypass surgery for cardiogenic shock
Authors: H. N. Hiltgren
Journal: JAMA (1978)

To the Editor.—  Recently, a reader inquired if there is any present indication for emergency  bypass surgery in patients with refractory cardiac power failure after myocardial infarction but no associated mitral valve insufficiency or ventricular septal defect (240:385,1978).  Three consultants gave an affirmative answer. One stated that the use of circulatory assistance particularly with the intra-aortic balloon pump (IABP) in combination with emergency cardiac surgery has reduced the mortality to between 30% and 40%. The consultant also added that coronary artery bypass graft surgery alone may on occasion save lives that otherwise would be lost. Four references were cited by the consultants to support their opinions.  To my knowledge, there are no published data including the four cited references that support this opinion. The combination of IABP and  surgery has not been evaluated using appropriate medical controls despite the obvious need for such studies. In one cited reference
Imaging of αvβ3 Expression by a Bifunctional Chimeric RGD Peptide not Cross-Reacting with αvβ5
Authors: Antonella Zannetti, Silvana Del Vecchio, Francesca Iommelli, Annarita Del Gatto, Stefania De Luca, Laura Zaccaro, Angela Papaccioli, Jvana Sommella, Mariarosaria Panico, Antonio Speranza, Paolo Grieco, Ettore Novellino, Michele Saviano, Carlo Pedone, Marco Salvatore
Journal: Clinical Cancer Research (2009)

Abstract Purpose: To test whether a novel bifunctional chimeric peptide comprising a cyclic Arg-Gly-Asp pentapeptide covalently bound to an echistatin domain can discriminate αvβ3 from αvβ5 integrin, thus allowing the in vivo selective visualization of αvβ3 expression by single-photon and positron emission tomography (PET) imaging. Experimental Design: The chimeric peptide was preliminarily tested for inhibition of αvβ3-dependent cell adhesion and competition of 125I-echistatin binding to membrane of stably transfected K562 cells expressing αvβ3 (Kαvβ3) or αvβ5 (Kαvβ5) integrin. The chimeric peptide was then conjugated with diethylenetriaminepentaacetic acid and labeled with 111In for single-photon imaging, whereas a one-step procedure was used for labeling the full-length peptide and a truncated derivative, lacking the last five C-terminal amino acids, with 18F for PET imaging. Nude mice bearing tumors from Kαvβ3, Kαvβ5, U87MG human glioblastoma, and A431 human epidermoid cells were subjected to single-photon and PET imaging. Results: Adhesion and competitive binding assays showed that the novel chimeric peptide selectively binds to αvβ3 integrin and does not cross-react with αvβ5. In agreement with in vitro findings, single-photon and PET imaging studies showed that the radiolabeled chimeric peptide selectively localizes in tumor xenografts expressing αvβ3 and fails to accumulate in those expressing αvβ5 integrin. When 18F-labeled truncated derivative was used for PET imaging, αvβ3- and αvβ5-expressing tumors were visualized, indicating that the five C-terminal amino acids are required to differentially bind the two integrins. Conclusion: Our findings indicate that the novel chimeric Arg-Gly-Asp peptide, having no cross-reaction with αvβ5 integrin, allows highly selective αvβ3 expression imaging and monitoring. (Clin Cancer Res 2009;15(16):5224–33)
Zoladex: a sustained-release, monthly luteinizing hormone-releasing hormone analogue for the treatment of advanced prostate cancer.
Authors: F R Ahmann, D L Citrin, H A deHaan, P Guinan, V C Jordan, W Kreis, M Scott, D L Trump
Journal: Journal of Clinical Oncology (1987)

Zoladex, a sustained-release luteinizing hormone--releasing hormone (LHRH) analogue administered by subcutaneous injection every 28 days, was evaluated at three dose levels in 46 men with untreated advanced prostate cancer. All three Zoladex doses yielded similar endocrinologic effects. After initial transient increases in serum luteinizing hormone, follicle-stimulating hormone, and testosterone concentrations, serum testosterone was suppressed uniformly to castration levels within 22 days. At a median follow-up of 41 weeks, Zoladex had maintained persistent suppression of serum testosterone. Measurements of serum Zoladex levels indicated that release of the drug from the injected depot was sustained over a period of 1 month and that there was no drug accumulation as evaluated over an initial 3-month period. No antibodies to Zoladex were detected. Tumor regression rates and side effects with Zoladex therapy were similar to those reported with daily injections of subcutaneous LHRH therapy. Signs and symptoms consistent with a brief tumor flare after the first injection of the LHRH analogue were noted in eight (17%) of the study entrants. Spinal cord compression was observed in two patients within 1 week from the onset of therapy. Zoladex is considered to be an effective, sustained-release LHRH analogue for the treatment of patients with prostate cancer.
The role of embodied change in perceiving and processing facial expressions of others
Authors: Pablo Briñol, Kenneth G. DeMarree, K. Rachelle Smith
Journal: Behavioral and Brain Sciences (2010)

Abstract The embodied simulation of smiles involves motor activity that often changes the perceivers' own emotional experience (e.g., smiling can make us feel happy). Although Niedenthal et al. mention this possibility, the psychological processes by which embodiment changes emotions and their consequences for processing other emotions are not discussed in the target article's review. We argue that understanding the processes initiated by embodiment is important for a complete understanding of the effects of embodiment on emotion perception.
Single-Donor, Marginal-Dose Islet Transplantation in Patients With Type 1 Diabetes
Authors: Bernhard J. Hering
Journal: JAMA (2005)

A therapeutic challenge.][3][4][5][6] However, for islet transplants to become a widespread clinical reality, additional advances are still needed.In particular, restoration of insulin independence must be achieved with a single donor, as is also the case with pancreas transplants, to reduce the risks and costs and increase the availability of islet transplantation.We designed a protocol to limit ischemic injury of islets during pancreas storage, permit initiation of potent immunotherapy prior to transplantation, and minimize calcineurin inhibitor exposure.
MRI Hyperintensities and Depressive Symptoms in a Community Sample of Individuals 60–64 Years Old
Authors: Anthony F. Jorm, Kaarin J. Anstey, Helen Christensen, Greg de Plater, Rajeev Kumar, Wei Wen, Perminder Sachdev
Journal: American Journal of Psychiatry (2005)

Previous studies have found associations of magnetic resonance imaging (MRI) signal hyperintensities with depression in the elderly. The present study investigates the association in a younger community sample (age 60-64 years) of depressed subjects and comparison groups for potential mediating and confounding variables.A subsample of 475 persons 60-64 years of age from a larger community survey underwent brain MRI scans. White matter hyperintensities were quantified by using an automated procedure, and basal ganglia hyperintensities were quantified by using semiquantitative visual ratings. The study also assessed depressive symptoms and use of antidepressant medication. Potential mediating or confounding variables assessed included physical disability, hypertension, stroke, diabetes, head injury, cortisol, thyroid-stimulating hormone, cognitive functioning, smoking, and alcohol use.Depressive symptoms were found to be related to total brain white matter hyperintensities but not to basal ganglia hyperintensities. However, associations disappeared when statistical adjustment was made for physical disability and smoking.Depressive symptoms are related to white matter hyperintensities in mid-adult life in a community sample. Physical disability appears to play an important role in this association.
Transplantation and Islet Topics
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2005)

This is the fourth in a series of articles on presentations at the American Diabetes Association Annual Meeting, Orlando, Florida, 4–8 June 2004.

The American Society of Transplantation (www.a-s-t.org) held a symposium at the June ADA meeting addressing the importance of diabetes following transplantation (1). Martha Pavlakis (Boston, MA) introduced the symposium, pointing out the importance of “long-term management, now that our focus is no longer [merely] getting the patient to survive 1 year.” Among the risks of transplantation are those of the surgery itself, those of chronic immunosuppression, and now those of new-onset diabetes, which “definitely affects graft and patient survival.”

Fernando G. Cosio (Rochester, MN) gave an overview of new-onset diabetes after transplantation in the U.S. Defining posttransplant diabetes mellitus (PTDM) as new onset of abnormal glucose metabolism following transplantation, he noted that it is common, that the incidence is increasing, and that the pathogenesis is complex. PTDM is associated with unexpectedly high risk of patient death, as well as with risk to the graft. One important question is whether this is “really new onset,” as the level of glucose tolerance of many patients is not carefully characterized before transplantation, and few studies assess patients for impaired glucose tolerance (IGT), or even for impaired fasting glucose (IFG). Indeed, rather crude diagnostic criteria are often used, such as the need for insulin administration, need for any glucose-lowering medicine, or assignment of billing codes for diabetes, so certainly many patients have diabetes that is not recognized. Given these reservations, the incidence of diabetes has been shown to increase with time after transplantation and appears to be higher among patients treated with tacrolimus than those treated with cyclosporine, at ∼15 vs. 10% for kidney and 18 vs. 8% for liver transplantation. Cosio reviewed his studies, with a linear increase in PTDM …
Transcription Factor YY1 Contributes to Tumor Growth by Stabilizing Hypoxia Factor HIF-1α in a p53-Independent Manner
Authors: Shourong Wu, Vivi Kasim, Mitsunobu R. Kano, Sayaka Tanaka, Shinsuke Ohba, Yutaka Miura, Kanjiro Miyata, Xueying Liu, Ako Matsuhashi, Ung-il Chung, Li Yang, Kazunori Kataoka, Nobuhiro Nishiyama, Makoto Miyagishi
Journal: Cancer Research (2013)

In response to hypoxic stress, hypoxia-inducible factor (HIF)-1α is a critical transcription factor regulating fundamental cellular processes, and its elevated expression level and activity are associated with poor outcomes in most malignancies. The transcription factor Yin Yang 1 (YY1) is an important negative regulator of the tumor suppressor factor p53. However, the role of YY1 under tumor hypoxic condition is poorly understood. Herein, we show that inhibition of YY1 reduced the accumulation of HIF-1α and its activity under hypoxic condition, and consequently downregulated the expression of HIF-1α target genes. Interestingly, our results revealed that the downregulation of HIF-1α by inhibiting YY1 is p53-independent. Functionally, the in vivo experiments revealed that inhibition of YY1 significantly suppressed growth of metastatic cancer cells and lung colonization and also attenuated angiogenesis in a p53-null tumor. Collectively, our findings unraveled a novel mechanism by which YY1 inhibition disrupts hypoxia-stimulated HIF-1α stabilization in a p53-independent manner. Therefore, YY1 inhibition could be considered as a potential tumor therapeutic strategy to give consistent clinical outcomes independent of p53 status.
Testing for intrauterine infection
Authors: Christian Vandenvelde, Martine Duys, Danièle Van Beers, Alberto Bertotto, Fabrizio Spinozzi, Robert Gerli, Fabrizia Paolini, None Paoletti, Cristopher Muscat, Gianni De Giorgi, FernandoM De Benedictis, Giuseppe Castellucci, Renato Vaccaro
Journal: The Lancet (1994)