tbuckley/cabot-search huggingface dataset:
Schistosomal stimulation of eosinophil production by human bone marrow in vitro
Authors: William A. Robinson, Maureen A. Entringer, Lotfy Ablel Naby Mahmoud, Carla J. Drebing
Journal: American Journal of Hematology (1983)

Abstract These studies were undertaken to determine if schistosomal and ragweed antigens incubated with human peripheral blood mononuclear cells (MNC) would stimulate the production of an eosinophil colony stimulating factor (CSF) which was active on human bone marrow. These studies have shown that schistosoma mansoni antigen in a concentration of 5 μg/ml incubated with MNC's from unsensitized individuals lead to production of a conditioned medium which did not stimulate an increased number of total colonies but did increase the number of eosinophil colonies (44 to 61 colonies). Ragweed antigen also stimulated increased eosinophil CSF (from 44 to 63 colonies). The granulocyte response to parasitic antigens almost invariably involves the eosinophil system. Eosinophils play a vital role in the control of these diseases in humans. Further understanding of the interaction of parasitic antigens with the granulopoietic system will hopefully give new and important clues as to how such parasites interact with man and how they are controlled.
A novel form of receptor interaction may contribute to -agonist resistance in asthma
Authors: G Warwick
Journal: Thorax (2006)

▴ McGraw DW, Mihlbachler KA, Schwarb MR, et al. Airway smooth muscle prostaglandin-EP1 receptors directly modulate β2-adrenergic receptors within a unique heterodimeric complex. J Clin Invest2006;116:1400–9[OpenUrl][1][CrossRef][2][PubMed][3][Web of Science][4] In attempting to elucidate the hitherto poorly understood action of the prostanoid-EP1 receptor, researchers in the US have uncovered a … [1]: {openurl}?query=rft.jtitle%253DJournal%2Bof%2BClinical%2BInvestigation%26rft.stitle%253DJCI%26rft.aulast%253DMcGraw%26rft.auinit1%253DD.%2BW.%26rft.volume%253D116%26rft.issue%253D5%26rft.spage%253D1400%26rft.epage%253D1409%26rft.atitle%253DAirway%2Bsmooth%2Bmuscle%2Bprostaglandin-EP1%2Breceptors%2Bdirectly%2Bmodulate%2Bbeta2-adrenergic%2Breceptors%2Bwithin%2Ba%2Bunique%2Bheterodimeric%2Bcomplex.%26rft_id%253Dinfo%253Adoi%252F10.1172%252FJCI25840%26rft_id%253Dinfo%253Apmid%252F16670773%26rft.genre%253Darticle%26rft_val_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Ajournal%26ctx_ver%253DZ39.88-2004%26url_ver%253DZ39.88-2004%26url_ctx_fmt%253Dinfo%253Aofi%252Ffmt%253Akev%253Amtx%253Actx [2]: /lookup/external-ref?access_num=10.1172/JCI25840&link_type=DOI [3]: /lookup/external-ref?access_num=16670773&link_type=MED&atom=%2Fthoraxjnl%2F61%2F8%2F683.1.atom [4]: /lookup/external-ref?access_num=000237259700036&link_type=ISI
Novel Mode of Action of Tylophorine Analogs as Antitumor Compounds
Authors: Wenli Gao, Wing Lam, Sanbao Zhong, Conrad Kaczmarek, David C. Baker, Yung-Chi Cheng
Journal: Cancer Research (2004)

Abstract Tylophorine and its analogs are phenanthroindolizidine alkaloids, several of which have been isolated from the Tylophora genus of plants. Evaluation of (+)-S-tylophorine [DCB-3500 (NSC-717335)] and its analog DCB-3503 (NSC-716802) in the National Cancer Institute tumor screen showed a fairly uniform and potent inhibition of cell growth in all 60 cell lines (GI50 ∼10−8 m). To further evaluate the antitumor potential of these compounds, we synthesized four tylophorine analogs, designated DCB-3500, DCB-3501, DCB-3502, and DCB-3503. All four tylophorine analogs exerted potent growth-inhibitory effects against HepG2, a human hepatocellular carcinoma cell line, and KB, a human nasopharyngeal carcinoma cell line. HepG2 cells were more sensitive than KB in terms of loss of clonogenicity. KB variants, which are resistant to etoposide, hydroxyurea, or camptothecin, have similar sensitivities to the tylophorine analogs, as do the parental KB cells. Treatment of nude mice bearing HepG2 tumor xenografts by i.p. injections of DCB-3503 at 6 mg/kg every 8 h on days 0 and 3 resulted in significant tumor growth suppression (P &amp;lt; 0.0001). Unlike conventional antitumor drugs, 3 μm DCB-3503 did not cause DNA breaks or apoptosis in HepG2 cells. Tylophorine analogs induced albumin expression and decreased α-fetoprotein expression in HepG2 cells, which suggests that tylophorine analogs could induce HepG2 differentiation. Tylophorine analogs had an inhibitory effect on cyclic AMP response elements, activator protein-1 sites, or nuclear factor-κB binding site-mediated transcriptions. In summary, these tylophorine analogs are a unique class of antitumor compounds that have a mode of action different from known antitumor drugs.
The effect of insecticide-treated bed nets on mortality of Gambian children
Authors: P.L. Alonso, S.W. Lindsay, J.R.M. Armstrong, A. de Francisco, F.C. Shenton, B.M. Greenwood, M. Conteh, K. Cham, A.G. Hill, P.H. David, G. Fegan, A.J. Hall
Journal: The Lancet (1991)
OC-053 AN 800 kcal nutritionally complete tube feed provides more adequate nutritional intake and is practically easier and quicker to use than currently used regimens
Authors: G P Hubbard, H Finch, R J Stratton
Journal: Gut (2012)

<h3>Introduction</h3> Some long term, chronically ill, tube fed patients with severe central nervous system impairment, may have lower energy requirements than predicted and need very low energy tube feeding regimens (∼800 kcal total energy per day) to maintain weight<sup>.1 2</sup> These patients receive a variety of different but nutritionally inadequate regimens, which can be complex and time consuming, with increased risk for errors and contamination<sup>3</sup> This study aimed to compare the nutritional outcomes and practicality of using current tube feeding regimens, vs a specifically developed ready made 800 kcal nutritionally complete tube feed. <h3>Methods</h3> Long term tube fed patients (n 15) with severe neuro-disorders (mean age: 51 yrs (SD 14), mean BMI: 24 kg/m<sup>2</sup> (SD 2.5), mean time receiving ≤1000 kcal/d: 3 yrs (SD 3.5)) requiring ∼800 kcal/d, received their current tube feeding regimen (either 1000 kcal nutritionally complete tube feeds or a mixture of feeding products (a tube feed, protein powder and powdered vitamin and mineral preparations)) for 1 wk, followed by 800 kcal/1000 ml per day of a ready made nutritionally complete tube feed (Nutrison 800 Complete Multi Fibre) for 4 wks. Nutritional outcomes (nutritional intakes, body weight) and practicality (ease of use, time to prepare and administer, acceptability and preference) were assessed weekly. NHS research ethics approval for this study was received in January 2011. <h3>Results</h3> The proportion of patients meeting their energy requirements (100% vs 47%), and their RNIs for protein (100% vs 87%) and vitamins &amp; minerals (100% vs 53%) was substantially greater with the ready made tube feed vs current regimens. Use of the ready made tube feed significantly increased the percentage of patients meeting their weight goals (86% vs 35%, p=0.003). 86% of nursing staff preparing and administering the regimens preferred the ready made tube feed (p=0.013) and rated it better for ease of preparation (100% vs 78%) and use (93% vs 79%). Preparation and administration of the current regimens took on average 15–55 min longer per patient per day than the ready made tube feed. <h3>Conclusion</h3> The ready made 800 kcal nutritionally complete tube feed provided a more nutritionally adequate intake than current tube feeding regimens. It was also practically easier and quicker to use than current regimens, allowing more appropriate utilisation of healthcare resource and time, providing an easier solution for the use of low energy tube feeding regimens in the home care setting. <h3>Competing interests</h3> G Hubbard Employee of: Nutricia, H Finch: None declared, R Stratton Employee of: Nutricia. <h3>References</h3> 1. <b>Dickerson RN</b>, Brown RO, Gervasio JG, <i>et al. J Am Coll Nutr</i> 1999;<b>18</b>:61–8. 2. <b>Leone</b>, Pencharz. <i>Clin Nutr</i> 2010;<b>29</b>:370–2. 3. <b>Hubbard</b>, <i>et al.</i> Presented at BAPEN. 2011.
Systematic Review: Comparative Effectiveness and Safety of Premixed Insulin Analogues in Type 2 Diabetes
Authors: Rehan Qayyum, Shari Bolen, Nisa Maruthur, Leonard Feldman, Lisa M. Wilson, Spyridon S. Marinopoulos, Padmini Ranasinghe, Muhammed Amer, Eric B. Bass
Journal: Annals of Internal Medicine (2008)

Background: Evidence comparing premixed insulin analogues (a mixture of rapid-acting and intermediate-acting insulin analogues) with other antidiabetic agents is urgently required to guide appropriate therapy. Purpose: To summarize the English-language literature on the effectiveness and safety of premixed insulin analogues compared with other antidiabetic agents in adults with type 2 diabetes. Data Sources: The authors searched MEDLINE, EMBASE, CINAHL, and the Cochrane Central Register of Controlled Trials from inception to February 2008 and sought unpublished data from the U.S. Food and Drug Administration, European Medicines Agency, and industry. Study Selection: Studies with control groups that compared premixed insulin analogues with another antidiabetic medication in adults with type 2 diabetes. Data Extraction: 2 reviewers using standardized protocols performed serial abstraction. Data Synthesis: Evidence from clinical trials was inconclusive for clinical outcomes, such as mortality. Therefore, the review focused on intermediate outcomes. Premixed insulin analogues were similar to premixed human insulin in decreasing fasting glucose levels, hemoglobin A1c levels, and the incidence of hypoglycemia but were more effective in decreasing postprandial glucose levels (mean difference, −1.1 mmol/L; 95% CI, −1.4 to −0.7 mmol/L [−19.2 mg/dL; 95% CI, −25.9 to −12.5 mg/dL]). Compared with long-acting insulin analogues, premixed insulin analogues were superior in decreasing postprandial glucose levels (mean difference, −1.5 mmol/L; CI, −1.9 to −1.2 mmol/L [−27.9 mg/dL; CI, −34.3 to −21.5 mg/dL]) and hemoglobin A1c levels (mean difference, −0.39% [CI, −0.50% to −0.28%]) but were inferior in decreasing fasting glucose levels (mean difference, 0.7 mmol/L; CI, 0.3 to 1.0 mmol/L [12.0 mg/dL; CI, 6.0 to 18.1 mg/dL]) and were associated with a higher incidence of hypoglycemia. Compared with noninsulin antidiabetic agents, premixed insulin analogues were more effective in decreasing fasting glucose levels (mean difference, −1.1 mmol/L; CI, −1.7 to −0.6 mmol/L [−20.5 mg/dL; CI, −29.9 to −11.2 mg/dL]), postprandial glucose levels (mean difference, −2.1 mmol/L; CI, −3.4 to −0.8 mmol/L [−37.4 mg/dL; CI, −61.0 to −13.7 mg/dL]), and hemoglobin A1c levels (mean difference, −0.49% [CI, −0.86% to −0.12%]) but were associated with a higher incidence of hypoglycemia. Limitations: The literature search was restricted to studies published in English. Data on clinical outcomes were limited. The small number of studies for each comparison limited assessment of between-study heterogeneity. Conclusion: Premixed insulin analogues provide glycemic control similar to that of premixed human insulin and may provide tighter glycemic control than long-acting insulin analogues and noninsulin antidiabetic agents.
Cytotoxic T Lymphocyte–Associated Antigen 4 Plays an Essential Role in the Function of Cd25+Cd4+ Regulatory Cells That Control Intestinal Inflammation
Authors: Simon Read, Vivianne Malmström, Fiona Powrie
Journal: The Journal of Experimental Medicine (2000)

It is now clear that functionally specialized regulatory T (Treg) cells exist as part of the normal immune repertoire, preventing the development of pathogenic responses to both self- and intestinal antigens. Here, we report that the Treg cells that control intestinal inflammation express the same phenotype (CD25+CD45RBlowCD4+) as those that control autoimmunity. Previous studies have failed to identify how CD25+ Treg cells function in vivo. Our studies reveal that the immune-suppressive function of these cells in vivo is dependent on signaling via the negative regulator of T cell activation cytotoxic T lymphocyte–associated antigen 4 (CTLA-4), as well as secretion of the immune-suppressive cytokine transforming growth factor β. Strikingly, constitutive expression of CTLA-4 among CD4+ cells was restricted primarily to Treg cells, suggesting that CTLA-4 expression by these cells is involved in their immune-suppressive function. These findings raise the possibility that Treg cell function contributes to the immune suppression characteristic of CTLA-4 signaling. Identification of costimulatory molecules involved in the function of Treg cells may facilitate further characterization of these cells and development of new therapeutic strategies for the treatment of inflammatory diseases.
Immigration as a Social Determinant of Health
Authors: Heide Castañeda, Seth M. Holmes, Daniel S. Madrigal, Maria-Elena DeTrinidad Young, Naomi Beyeler, James Quesada
Journal: Annual Review of Public Health (2014)

Although immigration and immigrant populations have become increasingly important foci in public health research and practice, a social determinants of health approach has seldom been applied in this area. Global patterns of morbidity and mortality follow inequities rooted in societal, political, and economic conditions produced and reproduced by social structures, policies, and institutions. The lack of dialogue between these two profoundly related phenomena-social determinants of health and immigration-has resulted in missed opportunities for public health research, practice, and policy work. In this article, we discuss primary frameworks used in recent public health literature on the health of immigrant populations, note gaps in this literature, and argue for a broader examination of immigration as both socially determined and a social determinant of health. We discuss priorities for future research and policy to understand more fully and respond appropriately to the health of the populations affected by this global phenomenon.
Monocyte chemotactic factors released from type II pneumocyte-like cells in response to TNF-alpha and IL-1alpha
Authors: S Koyama, E Sato, H Nomura, K Kubo, M Miura, T Yamashita, S Nagai, T Izumi
Journal: European Respiratory Journal (1999)

It has been reported that tumour necrosis factor (TNF)-alpha and interleukin (IL)-1 induce the release of monocyte chemotactic factors (MCF), including chemokines, from A549 cells, an alveolar type II cell line. However, the relative contribution of these chemokines to MCF is still uncertain. In the present study, the relative contribution of various chemokines released from A549 cells acting as MCF upon stimulation by TNF-alpha and IL-1alpha, was evaluated. TNF-alpha and IL-1alpha induced the release of MCF in a dose- and time-dependent manner (p&lt;0.001). The release of MCF was inhibited by cycloheximide and lipoxygenase inhibitors. Molecular sieve column chromatography revealed multiple peaks of MCF (near 60 kDa, 25-22 kDa, 15-13 kDa, 8 kDa, and 400 Da). Leukotriene B4 (LTB4) receptor-antagonists inhibited MCF by 50% after 24 h and 30% after 72 h. Monocyte chemoattractant protein-1 (MCP-1), transforming growth factor (TGF)-beta, "regulated on activation, normal T-cells, expressed and secreted" (RANTES), and granulocyte-macrophage colony- stimulating factor (GM-CSF) were released significantly in response to IL-1alpha and TNF-alpha, and antibodies to MCP-1, GM-CSF, and RANTES inhibited MCF activity by 40, 5 and 20% after 24 h, and by 50, 20, and 10% after 72 h, respectively. Each antibody or LTB4 receptor-antagonist inhibited the corresponding column chromatography-separated molecular weight peak of MCF. These data suggest that A549 cells release monocyte chemoattractant protein-1 as the predominant monocyte chemotactic factor rather than granulocyte-macrophage colony-stimulating factor, RANTES, and transforming growth factor-beta, and that leukotriene B4 is constitutively released as a monocyte chemotactic factor.
Short-Term Local Delivery of an Inhibitor of Ras Farnesyltransferase Prevents Neointima Formation In Vivo After Porcine Coronary Balloon Angioplasty
Authors: Lorraine M. Work, Allan R. McPhaden, Nigel J. Pyne, Susan Pyne, Roger M. Wadsworth, Cherry L. Wainwright
Journal: Circulation (2001)

Background Mitogenic stimuli present at the site of coronary arterial balloon injury contribute to the progression and development of a restenotic lesion, many signaling through a common pathway involving the small G protein p21 ras . Our aim was to demonstrate in biochemical studies that farnesyl protein transferase inhibitor III (FPTIII) is an inhibitor of p21 ras processing and that when it is given locally in vivo at the site of coronary balloon injury in a porcine model, it can inhibit neointima formation. Methods and Results FPTIII (1 to 25 μmol/L) concentration-dependently reduced p21 ras levels in porcine coronary artery smooth muscle cell membranes. FPTIII also prevented p42/p44 MAPK activation and DNA synthesis in response to platelet-derived growth factor in these cells at a concentration of 25 μmol/L. Application of 25 μmol/L FPTIII locally for 15 minutes to balloon-injured porcine coronary arteries in vivo prevented neointima formation assessed at 4 weeks, reduced proteoglycan deposition, and inhibited adventitial hypertrophy. Coronary arteries from FPTIII-treated pigs had no deterioration in contraction or in endothelium-dependent relaxation. Conclusions The study demonstrates in the pig that short-term local delivery of inhibitors of p21 ras -dependent mitogenic signal transduction prevents restenosis after balloon angioplasty.
Strategic Assessment of Risk and Risk Tolerance (StARRT) framework for return-to-play decision-making
Authors: Ian Shrier
Journal: British Journal of Sports Medicine (2015)

The sport medicine clinician is faced with return-to-play (RTP) decisions for every patient who wants to return to activity. The complex interaction of factors related to history, physical examination, testing, activity and baseline characteristics can make RTP decision-making challenging. Further, when reasoning is not explicit, unnecessary conflict can arise among clinicians themselves, or among clinicians and patients. This conflict can have negative health consequences for the patient. In 2010, a transparent framework for RTP decisions was proposed. However, some have identified limitations to the framework and found difficulties in its implementation. This paper presents a revised framework that addresses the limitations, and provides concrete examples of how to apply it in simple and complex cases.
Genetic evidence of heterogeneity in intrahepatic cholestasis of pregnancy
Authors: M Savander
Journal: Gut (2003)

<b>Background and aims:</b> The aim of this study was to investigate the genetic aetiology of intrahepatic cholestasis of pregnancy (ICP) and the impact of known cholestasis genes (<i>BSEP</i>, <i>FIC1</i>, and <i>MDR3</i>) on the development of this disease. <b>Patients and methods:</b> Sixty nine Finnish ICP patients were prospectively interviewed for a family history of ICP, and clinical features were compared in patients with familial ICP (patients with a positive family history, n=11) and sporadic patients (patients with no known family history of ICP, n=58). For molecular genetic analysis, 16 individuals from two independently ascertained Finnish ICP families were genotyped for the flanking markers for <i>BSEP</i>, <i>FIC1</i>, and <i>MDR3</i>. <b>Results:</b> The pedigree structures in 16% (11/69) of patients suggested dominant inheritance. Patients with familial ICP had higher serum aminotransferase levels and a higher recurrence risk (92% <i>v</i> 40%). Both segregation of haplotypes and multipoint linkage analysis excluded <i>BSEP</i>, <i>FIC1</i>, and <i>MDR3</i> genes in the studied pedigrees. Additionally, the MDR3 gene, previously shown to harbour mutations in ICP patients, was negative for mutations when sequenced in four affected individuals from the two families. <b>Conclusions:</b> These results support the hypothesis that the aetiology of ICP is heterogeneous and that ICP is due to a genetic predisposition in a proportion of patients. The results of molecular genetic analysis further suggest that the previously identified three cholestasis genes are not likely to be implicated in these Finnish ICP families with dominant inheritance.
Rho-Kinase Mediates Hyperglycemia-Induced Plasminogen Activator Inhibitor-1 Expression in Vascular Endothelial Cells
Authors: Yoshiyuki Rikitake, James K. Liao
Journal: Circulation (2005)

Elevated levels of plasminogen activator inhibitor-1 (PAI-1) are associated with myocardial infarction and stroke, especially in patients with diabetes. The induction of PAI-1 expression by hyperglycemia involves oxidative stress and protein kinase C (PKC). However, the mechanism by which hyperglycemia increases PAI-1 expression is unknown.Compared with normoglycemia, exposure of human endothelial cells to hyperglycemia, but not mannitol, increased Rho-kinase activity in a time- and concentration-dependent manner. This increase was inhibited by a PKC inhibitor, GF109203X, and antioxidants N-acetylcysteine (NAC) and reduced form of glutathione (GSH). This correlated with inhibition of hyperglycemia-induced PAI-1 expression by GF109203X, NAC, and GSH. Hyperglycemia-increased PAI-1 mRNA and protein levels were inhibited by Rho-kinase inhibitors hydroxyfasudil and Y27632 and by a dominant-negative mutant of Rho-kinase. The mechanism for this inhibition occurs at the level of gene transcription because Rho-kinase inhibitors repress hyperglycemia-stimulated PAI-1 promoter activity without affecting mRNA stability. Hyperglycemia failed to stimulate Rho-kinase activity and PAI-1 expression in heterozygous ROCK I-knockout murine endothelial cells.Hyperglycemia stimulates Rho-kinase activity via PKC- and oxidative stress-dependent pathways, leading to increased PAI-1 gene transcription. These results suggest that inhibition of ROCK I may be a novel therapeutic target for preventing thromboembolic complications of diabetes and cardiovascular disease.
Genetic control of cytolytic t-lymphocyte responses. II. The role of the host genotype in parental leads to F1 radiation chimeras in the control of the specificity of cytolytic T-lymphocyte responses to trinitrophenyl-modified syngeneic cells.
Authors: P Billings, S J Burakoff, M E Dorf, B Benacerraf
Journal: The Journal of Experimental Medicine (1978)

Bone marrow cells from C3H (H-2k) mice, a strain that does not exhibit cross-reactive lysis of trinitrophenyl (TNP)-modified allogeneic targets, were allowed to mature in heavily irradiated (B6 times C3H)F1 (H-2b/k) recipients, an F1 hybrid that does demonstrate cross-reactive lysis. Spleen cells from these chimeric mice were removed after 3-4 mo and by H-2 typing shown to be of C3H origin. These cells were found to be tolerant to B6 alloantigens by mixed lymphocyte reaction and cell-mediated cytotoxicity and, when stimulated in vitro with TNP-modified syngeneic cells, now cross-reactively lysed TNP-modified allogeneic targets. These studies demonstrate that the host environment where T cells differentiate influences the specificity of the primary cytolytic T-lymphocyte (CTL) response to TNP-modified syngeneic antigens.