tbuckley/cabot-search huggingface dataset:
Cardiopulmonary effects of iloprost in experimental acute lung injury
Authors: R. Dembinski, W. Brackhahn, D. Henzler, A. Rott, R. Bensberg, R. Kuhlen, R. Rossaint
Journal: European Respiratory Journal (2005)

Iloprost, a prostacyclin analogue with a prolonged plasma half-life has beneficial effects in chronic pulmonary hypertension, whereas the effects in acute lung injury (ALI) are unknown. The present study was performed to evaluate the cardiopulmonary effects of iloprost in experimental ALI. ALI was induced in 18 pigs by repeated lung lavage. Animals were randomised to controls, i.v. or inhaled iloprost for 15 min. Haemodynamics, gas exchange and ventilation–perfusion distribution were measured at the end of iloprost application and after 1 and 2 h. As a short-term effect, both i.v. and inhaled iloprost significantly decreased pulmonary artery pressure without major effects on gas exchange or systemic haemodynamics. After 1 and 2 h, a reduction of pulmonary hypertension was no longer present. As a long-term effect, inhaled, but not i.v. , iloprost decreased pulmonary shunt and significantly improved gas exchange after 1 and 2 h. In conclusion, the single application of iloprost revealed short-term pulmonary vasodilation without other major cardiopulmonary effects. However, inhaled iloprost improved gas exchange due to a decrease of pulmonary shunt as a long-term effect, possibly as a result of a reduction of lung oedema formation.
Microvascular Responses to Inhibition of Nitric Oxide Production
Authors: Iwao Kurose, Robert Wolf, Matthew B. Grisham, Tak Yee Aw, Robert D. Specian, D. Neil Granger
Journal: Circulation Research (1995)

Abstract The objective of this study was to assess the potential contribution of hydrogen peroxide (H 2 O 2 ) to the leukocyte–endothelial cell adhesion and increased microvascular permeability observed in rat mesenteric venules after inhibition of nitric oxide synthesis with N G -nitro- l -arginine methyl ester (L-NAME). Leukocyte adherence and emigration and leakage of fluorescein isothiocyanate–labeled albumin were monitored in postcapillary venules before and after exposure of the tissue to L-NAME. H 2 O 2 production in mesenteric tissue was monitored by using dihydrorhodamine 123 (DHR), the H 2 O 2 -sensitive fluorochrome. L-NAME elicited a rapid increase in both the rate of albumin extravasation and oxidation of DHR, which was followed by an increased adherence and emigration of leukocytes in postcapillary venules. Treatment with either catalase or dimethylthiourea attenuated the L-NAME–induced oxidative stress, albumin leakage, and leukocyte–endothelial cell adhesion. Oxidation of DHR was enhanced in animals treated with either 3-amino-1,2,4-triazole (ATZ), an inhibitor of endogenous catalase, or a combination of ATZ and maleic acid diethyl ester, which depletes intracellular glutathione. Animals receiving a CD11/CD18-specific antibody to prevent leukocyte adhesion/emigration exhibited a reduced oxidation of DHR in response to L-NAME. These findings indicate that most of the H 2 O 2 (and secondarily derived oxidants) generated in mesenteric tissue exposed to an inhibitor of nitric oxide production is due to accumulation of activated leukocytes.
Barriers to Achieving Glycemic Targets: Who Omits Insulin and Why?
Authors: Katie Weinger, Elizabeth A. Beverly
Journal: Diabetes Care (2010)

Improved glycemic control in people with diabetes delays the onset and progression of severe microvascular complications of diabetes (1,2). Despite advances in pharmacotherapy and diabetes treatment devices and the emphasis placed on treatment adherence over the last decade, National Health and Nutrition Examination Survey (NHANES) data showed 45% of patients with diabetes did not achieve glycemic targets of <7% (3). Although some patients with diabetes may be undertreated (e.g., inappropriate treatment regimens, psychosocial issues that require adjustment in therapeutic targets), one reason for poor glycemic control is patients' difficulty in following treatment prescriptions and recommendations for diabetes self-care.

The number of diabetes medications prescribed and the number of people using diabetes medications have increased exponentially as a result of increasing prevalence rates in type 2 diabetes. Insulin is an extremely effective glucose-lowering treatment that is a medical requirement for type 2 diabetes when the pancreas fails. Approximately 27% of all people with diabetes take insulin (4). Surprisingly little is known about factors related to adherence to medication prescriptions and, more specifically, intentional insulin omission and how underlying motivations for insulin omission differ by type of diabetes.

A recent study in this issue of Diabetes Care by Peyrot et al. (5) brings this issue to the forefront. The purpose of this study was to explore the frequency of intentional insulin omission and the factors associated with this behavior in a sample of 502 U.S. adults self-identified as taking insulin by injection to treat either type 1 or type 2 diabetes. Fifty-seven percent of the respondents reported omitting insulin injections, with 20% omitting insulin injections regularly. Regression analyses identified older age, lower income and education, type 2 diabetes, poor diet adherence, more frequently prescribed injections, interference with daily activities, pain, and embarrassment as independent risk factors for intentional insulin omission. …
P195 Plume characteristics of fluticasone propionate/formoterol pMDI compared with fluticasone propionate/salmeterol pMDI: Abstract P195 Table 1.
Authors: B Johal, S Murphy, J Marshall
Journal: Thorax (2013)

<h3>Background</h3> It has been suggested that aerosol inhaler characteristics such as fine particle size distribution, low plume velocity, and long duration of the aerosol cloud may assist coordination of inhalation with actuation, improve lung deposition, and reduce oropharyngeal deposition. This study compared 2 ICS/LABA combination HFA pMDI inhalers: fluticasone propionate/formoterol 125/5 μg (FP/FORM; <b><i>flutiform</i></b><sup>®</sup>) and fluticasone propionate/salmeterol 125/50 μg (FP/SAL; <b><i>Seretide</i></b><sup>®</sup><b><i> Evohaler</i></b><sup>®</sup>). <h3>Methods</h3> Inhalers were operated according to their respective patient information leaflets, and were fired into still air. Plume data were recorded using an Oxford Lasers EnVision Pharma system with high speed CMOS camera and short-pulse laser light source. VidPIV 4.6 &amp; EnVision 1.1.5 software was used to analyse the data and assess velocity and other characteristics of the plume at set intervals from the actuator (up to 9.5 cm which is representative of the distance from mouth to throat). <h3>Results</h3> FP/FORM pMDI had slower maximum velocity of plume than did FP/SAL at the distances measured (table). Furthermore, the duration of plume lasted approximately 50% longer over the distance measured with FP/FORM than with FP/SAL. <h3>Conclusion</h3> FP/FORM has a slower and more prolonged plume compared with FP/SAL. This may help synchronise aerosol availability and inhalation and may lead to less oropharyngeal deposition and better lung deposition.
Dendritic cells require a systemic type I interferon response to mature and induce CD4+ Th1 immunity with poly IC as adjuvant
Authors: M. Paula Longhi, Christine Trumpfheller, Juliana Idoyaga, Marina Caskey, Ines Matos, Courtney Kluger, Andres M. Salazar, Marco Colonna, Ralph M. Steinman
Journal: The Journal of Experimental Medicine (2009)

Relative to several other toll-like receptor (TLR) agonists, we found polyinosinic:polycytidylic acid (poly IC) to be the most effective adjuvant for Th1 CD4+ T cell responses to a dendritic cell (DC)–targeted HIV gag protein vaccine in mice. To identify mechanisms for adjuvant action in the intact animal and the polyclonal T cell repertoire, we found poly IC to be the most effective inducer of type I interferon (IFN), which was produced by DEC-205+ DCs, monocytes, and stromal cells. Antibody blocking or deletion of type I IFN receptor showed that IFN was essential for DC maturation and development of CD4+ immunity. The IFN-AR receptor was directly required for DCs to respond to poly IC. STAT 1 was also essential, in keeping with the type I IFN requirement, but not type II IFN or IL-12 p40. Induction of type I IFN was mda5 dependent, but DCs additionally used TLR3. In bone marrow chimeras, radioresistant and, likely, nonhematopoietic cells were the main source of IFN, but mda5 was required in both marrow–derived and radioresistant host cells for adaptive responses. Therefore, the adjuvant action of poly IC requires a widespread innate type I IFN response that directly links antigen presentation by DCs to adaptive immunity.
Renal replacement therapy in a patient with phocomelia
Authors: P. J Gibbs, P. J Friend, C. R Darby
Journal: Journal of the Royal Society of Medicine (2003)

The drug thalidomide, launched in 1954 as an antiemetic for use in pregnancy, was responsible for an epidemic of birth deformities (limb phocomelia) that affected some 2500 children worldwide, about 400 of these in the UK. When this condition is complicated by end-stage renal failure, treatment presents exceptional difficulties.
Judgment under uncertainty: Evolution may not favor a probabilistic calculus
Authors: Lev R. Ginzburg, Charles Janson, Scott Ferson
Journal: Behavioral and Brain Sciences (1996)

Abstract The environment in which humans evolved is strongly and positively autocorrelated in space and time. Probabilistic judgments based on the assumption of independence may not yield evolutionarily adaptive behavior. A number of “faults” of human reasoning are not faulty under fuzzy arithmetic, a nonprobabilistic calculus of reasoning under uncertainty that may be closer to that underlying human decision making.
Unique phenotype of hepatocellular cancers with exon-3 mutations in beta-catenin gene
Authors: Benjamin Cieply, Gang Zeng, Tracy Proverbs‐Singh, David A. Geller, Satdarshan P. S. Monga
Journal: Hepatology (2008)

Wnt/β-catenin signaling plays an important role in liver development and regeneration. Its aberrant activation, however, is observed in a subset of primary hepatocellular cancers (HCCs). In the current study, we compare and contrast the tumor characteristics of HCC in the presence or absence of mutations in the β-catenin gene (CTNNB1). Frozen HCCs (n = 32), including five fibrolamellar (FL) variants, and control livers (n = 3) from Health Sciences Tissue Bank and Department of Surgery at the University of Pittsburgh Medical Center, were examined for mutations in CTNNB1, protein levels of β-catenin, tyrosine-654-phosphorylated-β-catenin (Y654-β-catenin), and glutamine synthetase (GS). Missense mutations in the exon-3 of CTNNB1were identified in 9/32 HCCs. Total β-catenin levels were higher than controls in most tumors; however, GS was exclusively increased in HCCs with mutations. Phenotypically, greater percentages of mutated HCCs showed macrovascular and microvascular invasion. Also, the tumor size was greater than double in mutated HCCs. High levels of total β-catenin protein were observed in multinodular tumors independent of β-catenin mutations. In addition, significant cases with mutations showed absence of cirrhosis. Finally, the highest levels of Y654-β-catenin were exclusively observed in fibrolamellar (FL)-HCC cases. Conclusion: Thus, HCCs that harbor missense mutations in exon-3 of CTNNB1 exhibit, histologically, a more aggressive phenotype. Also, CTNNB1 mutations might lead to HCC in the absence of cirrhosis. Finally, FL-HCC cases display a unique up-regulation of tyrosine-phosphorylated-β-catenin, suggesting robust receptor tyrosine kinase signaling in this tumor type. (HEPATOLOGY 2009.)
Relationship Between Ragweed Specific IgE and Acute Allergic Events During Ragweed Rush Immunotherapy (RIT)
Authors: P.S. Jonsson-Razdan, J. Stokes, P.D. Turner, R. Walters, W.W. Busse, J.N. Kline, Z.K. Ballas, T.B. Casale
Journal: Journal of Allergy and Clinical Immunology (2012)
Ionizing Radiation and Chemotherapeutic Drugs Induce Apoptosis in Lymphocytes in the Absence of FAS or Fadd/Mort1 Signaling
Authors: Kim Newton, Andreas Strasser
Journal: The Journal of Experimental Medicine (2000)

Ionizing radiation and cytotoxic drugs used in the treatment of cancer induce apoptosis in many cell types, including tumor cells. It has been reported that tumor cells treated with anticancer drugs increase surface expression of Fas ligand (FasL) and are killed by autocrine or paracrine apoptosis signaling through Fas (Friesen, C., I. Herr, P.H. Krammer, and K.-M. Debatin. 1996. Nat. Med. 2:574–577). We show that lymphocytes that cannot be killed by FasL, such as those from Fas-deficient lpr mice or transgenic mice expressing a dominant negative mutant of Fas-associated death domain protein (FADD/MORT1), are as sensitive as normal lymphocytes to killing by gamma radiation or the cytotoxic drugs cis-platin, doxorubicin, and etoposide. In contrast, p53 deficiency or constitutive expression of Bcl-2 markedly increased the resistance of lymphocytes to gamma radiation or anticancer drugs but had no effect on killing by FasL. Consistent with these observations, lpr and wild-type T cells both had a reduced capacity for mitogen-induced proliferation after drug treatment, whereas bcl-2 transgenic or p53-deficient T cells retained significant clonogenic potential. These results demonstrate that apoptosis induced by ionizing radiation or anticancer drugs requires p53 and is regulated by the Bcl-2 protein family but does not require signals transduced by Fas and FADD/MORT1.
Loss of SNAIL Regulated miR-128-2 on Chromosome 3p22.3 Targets Multiple Stem Cell Factors to Promote Transformation of Mammary Epithelial Cells
Authors: PengXu Qian, Arindam Banerjee, Zheng-Sheng Wu, Xiao Zhang, Hong Wang, Vijay Pandey, Wei-Jie Zhang, Xue-Fei Lv, Sheng Tan, Peter E. Lobie, Tao Zhu
Journal: Cancer Research (2012)

A discontinuous pattern of LOH at chromosome 3p has been reported in 87% of primary breast cancers. Despite the identification of several tumor suppressor genes in this region, there has yet to be a detailed analysis of noncoding RNAs including miRNAs in this region. In this study, we identified 16 aberrant miRNAs in this region and determined several that are frequently lost or amplified in breast cancer. miR-128-2 was the most commonly deleted miRNA. Embedded in the intron of the ARPP21 gene at chromosome 3p22.3, miR-128-2 was frequently downregulated along with ARPP21 in breast cancer, where it was negatively associated with clinicopathologic characteristics and survival outcome. Forced expression of miR-128 impeded several oncogenic traits of mammary carcinoma cells, whereas depleting miR-128-2 expression was sufficient for oncogenic transformation and stem cell-like behaviors in immortalized nontumorigenic mammary epithelial cells, both in vitro and in vivo. miR-128-2 silencing enabled transforming capacity partly by derepressing a cohort of direct targets (BMI1, CSF1, KLF4, LIN28A, NANOG, and SNAIL), which together acted to stimulate the PI3K/AKT and STAT3 signaling pathways. We also found that miR-128-2 was directly downregulated by SNAIL and repressed by TGF-β signaling, adding 2 additional negative feedback loops to this network. In summary, we have identified a novel TGF-β/SNAIL/miR-128 axis that provides a new avenue to understand the basis for oncogenic transformation of mammary epithelial cells.
Distinct contribution of IL-6, TNF-α, IL-1, and IL-10 to T cell–mediated spontaneous autoimmune arthritis in mice
Authors: Hiroshi Hata, Noriko Sakaguchi, Hiroyuki Yoshitomi, Yoichiroh Iwakura, Kenji Sekikawa, Yoshiaki Azuma, Chieko Kanai, Eiko Moriizumi, Takashi Nomura, Takashi Nakamura, Shimon Sakaguchi
Journal: Journal of Clinical Investigation (2004)

Cytokines play key roles in spontaneous CD4+ T cell–mediated chronic autoimmune arthritis in SKG mice, a new model of rheumatoid arthritis. Genetic deficiency in IL-6 completely suppressed the development of arthritis in SKG mice, irrespective of the persistence of circulating rheumatoid factor. Either IL-1 or TNF-α deficiency retarded the onset of arthritis and substantially reduced its incidence and severity. IL-10 deficiency, on the other hand, exacerbated disease, whereas IL-4 or IFN-γ deficiency did not alter the disease course. Synovial fluid of arthritic SKG mice contained high amounts of IL-6, TNF-α, and IL-1, in accord with active transcription of these cytokine genes in the afflicted joints. Notably, immunohistochemistry revealed that distinct subsets of synovial cells produced different cytokines in the inflamed synovium: the superficial synovial lining cells mainly produced IL-1 and TNF-α, whereas scattered subsynovial cells produced IL-6. Thus, IL-6, IL-1, TNF-α, and IL-10 play distinct roles in the development of SKG arthritis; arthritogenic CD4+ T cells are not required to skew to either Th1 or Th2; and the appearance of rheumatoid factor is independent of joint inflammation. The results also indicate that targeting not only each cytokine but also each cell population secreting distinct cytokines could be an effective treatment of rheumatoid arthritis.
National, regional, and global trends in serum total cholesterol since 1980: systematic analysis of health examination surveys and epidemiological studies with 321 country-years and 3·0 million participants
Authors: Farshad Farzadfar, Mariel M Finucane, Goodarz Danaei, Pamela M Pelizzari, Melanie J Cowan, Christopher J Paciorek, Gitanjali M Singh, John K Lin, Gretchen A Stevens, Leanne M Riley, Majid Ezzati
Journal: The Lancet (2011)
The ERα coactivator, HER4/4ICD, regulates progesterone receptor expression in normal and malignant breast epithelium
Authors: Jerzy Rokicki, Partha M Das, Jennifer M Giltnane, Olivia Wansbury, David L Rimm, Beatrice A Howard, Frank E Jones
Journal: Molecular Cancer (2010)

The HER4 intracellular domain (4ICD) is a potent estrogen receptor (ERalpha) coactivator with activities in breast cancer and the developing mammary gland that appear to overlap with progesterone receptor (PgR). In fact, 4ICD has recently emerged as an important regulator and predictor of tamoxifen response, a role previously thought to be fulfilled by PgR. Here we investigated the possibility that the 4ICD coactivator regulates PgR expression thereby providing a mechanistic explanation for their partially overlapping activities in breast cancer. We show that 4ICD is both sufficient and necessary to potentiate estrogen stimulation of gene expression. Suppression of HER4/4ICD expression in the MCF-7 breast tumor cell line completely eliminated estrogen stimulated expression of PgR. In addition, the HER4/4ICD negative MCF-7 variant, TamR, failed to express PgR in response to estrogen. Reintroduction of wild-type HER4 but not the gamma-secretase processing mutant HER4V673I into the TamR cell line restored PgR expression indicating that 4ICD is an essential PgR coactivator in breast tumor cells. These results were substantiated in vivo using two different physiologically relevant experimental systems. In the mouse mammary gland estrogen regulates expression of PgR-A whereas expression of PgR-B is estrogen independent. Consistent with a role for 4ICD in estrogen regulated PgR expression in vivo, PgR-A, but not PgR-B, expression was abolished in HER4-null mouse mammary glands during pregnancy. Coexpression of PgR and 4ICD is also commonly observed in ERalpha positive breast carcinomas. Using quantitative AQUA IHC technology we found that 4ICD potentiated PgR expression in primary breast tumors and the highest levels of PgR expression required coexpression of ERalpha and the 4ICD coactivator. In summary, our results provide compelling evidence that 4ICD is a physiologically important ERalpha coactivator and 4ICD cooperates with ERalpha to potentiate PgR expression in the normal and malignant breast. We propose that direct coupling of these signaling pathways may have important implications for mammary development, breast carcinogenesis, and patient response to endocrine therapy.
First-Trimester Follistatin-Like-3 Levels in Pregnancies Complicated by Subsequent Gestational Diabetes Mellitus
Authors: Ravi Thadhani, Camille E. Powe, May Lee Tjoa, Eliyahu Khankin, Jun Ye, Jeffrey Ecker, Alan Schneyer, S. Ananth Karumanchi
Journal: Diabetes Care (2009)

OBJECTIVE To determine whether maternal levels of follistatin-like-3 (FSTL3), an inhibitor of activin and myostatin involved in glucose homeostasis, are altered in the first trimester of pregnancies complicated by subsequent gestational diabetes mellitus (GDM). RESEARCH DESIGN AND METHODS This was a nested case-control study of subjects enrolled in a prospective cohort of pregnant women with and without GDM (≥2 abnormal values on a 100-g glucose tolerance test at ∼28 weeks of gestation). We measured FSTL3 levels in serum collected during the first trimester of pregnancy. Logistic regression analyses were used to determine the risk of GDM. RESULTS Women who developed GDM (n = 37) had lower first-trimester serum levels of FSTL3 compared with women who did not (n = 127) (median 10,789 [interquartile range 7,013–18,939] vs. 30,670 [18,370–55,484] pg/ml, P &amp;lt; 0.001). When subjects were divided into tertiles based on FSTL3 levels, women with the lowest levels demonstrated a marked increase in risk for developing GDM in univariate (odds ratio 11.2 [95% CI 3.6–35.3]) and multivariate (14.0 [4.1–47.9]) analyses. There was a significant negative correlation between first-trimester FSTL3 levels and ∼28-week nonfasting glucose levels (r = −0.30, P &amp;lt; 0.001). CONCLUSIONS First-trimester FSTL3 levels are associated with glucose intolerance and GDM later in pregnancy.
Reviewing the Reviews
Authors: John Joyce, Sophia Rabe-Hesketh, Simon Wessely
Journal: JAMA (1998)

Objective.—To test the hypothesis that the selection of literature in review articles is unsystematic and is influenced by the authors' discipline and country of residence.Data Sources.—Reviews in English published between 1980 and March 1996 in MEDLINE, EMBASE (BIDS), PSYCHLIT, and Current Contents were searched.Study Selection.—Reviews of chronic fatigue syndrome (CFS) were selected. Articles explicitly concerned with a specialty aspect of CFS and unattributed, unreferenced, or insufficiently referenced articles were discarded.Data Extraction.—Record of data sources in each review was noted as was the departmental specialty of the first author and his or her country of residence. The references cited in each index paper were tabulated by assigning them to 6 specialty categories, by article title, and by assigning them to 8 categories, by country of journal publication.Data Synthesis.—Of 89 reviews, 3 (3.4%) reported on literature search and described search method. Authors from laboratory-based disciplines preferentially cited laboratory references, while psychiatry-based disciplines preferentially cited psychiatric literature (P=.01). A total of 71.6% of references cited by US authors were from US journals, while 54.9% of references cited by United Kingdom authors were published in United Kingdom journals (P=.001).Conclusion.—Citation of the literature is influenced by review authors' discipline and nationality.