tbuckley/cabot-search huggingface dataset:
Moderate Daily Intake of Red Wine Inhibits Mural Thrombosis and Monocyte Tissue Factor Expression in an Experimental Porcine Model
Authors: L. Casani, E. Segales, G. Vilahur, A. Bayes de Luna, L. Badimon
Journal: Circulation (2004)

Background— Moderate consumption of red wine has been epidemiologically associated with a reduction in cardiovascular disease, but its mechanism of action is not fully understood. The objective was to study whether the protective effects of a daily intake of red wine (Tempranillo, 12.8% alcohol vol/vol) could be related to inhibition of thrombosis in an experimental model of diet-induced hyperlipemia. Methods and Results— For 100 days, animals were fed a western-type proatherogenic diet containing 2% cholesterol and 20% saturated fat. Three doses of red wine were studied (20, 30, and 40 g wine-ethanol/d) and compared with placebo-control animals not taking any wine. Thrombosis under flow conditions was evaluated by radioisotopic quantification of deposited platelets on damaged arteries. Changes in RhoA translocation in platelets and monocyte tissue factor expression were also analyzed. Mural platelet deposition was significantly reduced in animals ingesting red wine with their food. Expression of RhoA in the platelet cytoplasm (inactive form) was increased in wine-fed animals. Tissue factor mRNA expression in lipopolysaccharide-stimulated monocytes was reduced in wine-fed animals. Total cholesterol levels were not significantly different among groups. Conclusions— Moderate red wine intake significantly reduces platelet deposition triggered by damaged vessel wall, partially explained by inhibition of RhoA translocation to the platelet membrane. Hence, a daily moderate intake of wine seems to inhibit different pathways that converge in a reduced thrombotic risk on vessel wall injury.
Abstract 2002: Importance of Glomerular Filtration Rate Formula for Determining Chronic Kidney Disease and Clinical Care in Patients with Acute Coronary Syndromes
Authors: Chiara Melloni, Eric D Peterson, Anita Y Chen, Lynda A Szczech, L. Kristin Newby, Robert A Harrington, W. Brian Gibler, W. Magnus Ohman, Sarah A Spinler, Matthew T Roe, Karen P Alexander
Journal: Circulation (2006)

Background: Assessment of renal function is important for antithrombotic dose adjustment and predicting risk of adverse events in ACS patients (pts). Cockcroft-Gault (C-G) and Modification of Diet ...
Treatment of Cynanche Maligna
Authors: W. A. Bryden
Journal: BMJ (1857)

<h3>OBJECTIVE:</h3> The aim of this prospective study was to analyze the rate and characteristics of acute poisoning cases admitted to adult intensive care unit (ICU). <h3>METHODS:</h3> All cases of acute poisoning admitted to ICU of the Harran University Hospital, Turkey, between July 2002 and May 2005, were included in this study. Clinical, laboratory, and demographic characteristics, type of poison and patient9s outcomes were recorded. <h3>RESULTS:</h3> There were 86 poisoning cases among 844 patients admitted to the ICU. The mean age was 26 ± 9&nbsp;years and the majority of the patients (56.9%) were 15-24&nbsp;years of ages. Eighty percent of acute poisonings were self-inflicted and 65.2% of these patients were singles. Medical drugs overdose were the major cause (51.2%) of intoxication followed by agricultural chemicals (37.2%). The most frequently involved medicinal drugs were benzodiazepines, antidepressants and analgesics. Eleven patients in pesticides-rodenticides and 9 patients in other medical drugs poisoning have required mechanical ventilation between 1-12 days. The duration of the intensive care stay was 6.4 ± 4.3 days. Five cases (5.8%) with acute poisonings were fatal. <h3>CONCLUSION:</h3> There was a high rate of suicides attempt in young singles, predominantly female population. These data were the highest agricultural activity of the country that provide important information about the characteristics of poisoning at the city.
GENETIC CONTROL OF THE IMMUNE RESPONSE
Authors: F. Carl Grumet
Journal: The Journal of Experimental Medicine (1972)

The kinetics of antibody formation after immunization with the synthetic polypeptide poly-L(Tyr, Glu)-poly-D, L-Ala--poly-L-Lys [(T, G)-A--L] in aqueous solution were studied in genetically high (H-2(b)) and low (H-2(k)) responder strains of mice. During the 1st wk after immunization both strains developed brisk primary responses consisting of IgM antibody. With subsequent antigen challenge, only the high responder mice showed immunological memory, producing high titers of IgG antibody. In contrast, the low responder mice continued to make a persistent low level of IgM antibody and appeared unreactive to secondary or tertiary antigen challenge. These data are consistent with the hypothesis that the immune response-1 gene [controlling response to (T, G)-A--L] exerts its effect on the immune response at the time of switchover from IgM to IgG antibody production.
T-bet Controls Autoaggressive CD8 Lymphocyte Responses in Type 1 Diabetes
Authors: Amy E. Juedes, Evelyn Rodrigo, Lisa Togher, Laurie H. Glimcher, Matthias G. von Herrath
Journal: The Journal of Experimental Medicine (2004)

The T-box transcription factor T-bet is known to control lineage commitment and interferon-γ production by T helper 1 (Th1) CD4 lymphocytes. We report here that T-bet is essential for development of CD8 lymphocyte-dependent autoimmune diabetes (type 1 diabetes [T1D]) in the rat insulin promoter–lymphocytic choriomeningitis virus (LCMV) transgenic model for virally induced T1D. In the absence of T-bet, autoaggressive (anti-LCMV) CD8 lymphocytes were reduced in number and produced less IFN-γ, but increased IL-2 compared with controls. Further analysis showed that T-bet intrinsically controls the generation, but not apoptosis, maintenance, or secondary expansion of antiviral effector/memory CD8 lymphocytes. This observation points toward a therapeutic opportunity for the treatment of T1D and other autoimmune disorders.
Lack of Association of the APOL1 G3 Haplotype in African Americans with ESRD
Authors: Nicholette D. Palmer, Maggie C.Y. Ng, Carl D. Langefeld, Jasmin Divers, Janice P. Lea, Mark D. Okusa, Robert P. Kimberly, Donald W. Bowden, Barry I. Freedman
Journal: Journal of the American Society of Nephrology (2014)

Apolipoprotein L1 gene (APOL1) G1 and G2 variants are strongly associated with progressive nondiabetic nephropathy in populations with recent African ancestry. Selection for these variants occurred as a result of protection from human African trypanosomiasis (HAT). Resequencing of this region in 10 genetically and geographically distinct African populations residing in HAT endemic regions identified eight single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium and comprising a novel G3 haplotype. To determine whether the APOL1 G3 haplotype was associated with nephropathy, G1, G2, and G3 SNPs and 70 ancestry informative markers spanning the genome were genotyped in 937 African Americans with nondiabetic ESRD, 965 African Americans with type 2 diabetes–associated ESRD, and 1029 non-nephropathy controls. In analyses adjusting for age, sex, APOL1 G1/G2 risk (recessive), and global African ancestry, the G3 haplotype was not significantly associated with ESRD (P=0.05 for nondiabetic ESRD, P=0.57 for diabetes-associated ESRD, and P=0.27 for all-cause ESRD). We conclude that variation in APOL1 G3 makes a nominal, if any, contribution to ESRD in African Americans; G1 and G2 variants explain the vast majority of nondiabetic nephropathy susceptibility.
<i>De novo</i>Induction of a Cancer/Testis Antigen by 5-Aza-2′-Deoxycytidine Augments Adoptive Immunotherapy in a Murine Tumor Model
Authors: Z. Sheng Guo, Julie A. Hong, Kari R. Irvine, G. Aaron Chen, Paul J. Spiess, Yang Liu, Gang Zeng, John R. Wunderlich, Dao M. Nguyen, Nicholas P. Restifo, David S. Schrump
Journal: Cancer Research (2006)

Recent studies suggest that immunotherapy targeting specific tumor-associated antigens (TAAs) may be beneficial in cancer patients. However, most of these TAAs are tumor type specific and heterogeneous among patients, thus limiting their applications. Here, we describe the de novo induction of a cancer/testis antigen (CTA) for immunotherapy of tumors of various histologies. The murine CTA P1A, normally expressed only in a few tumor lines, could be induced de novo in all P1A-negative cancer lines of eight histologic origins in vitro and in various murine xenografts by systemic administration of 5-aza-2'-deoxycytidine. The induction of P1A expression correlated strongly with demethylation of the CpG island in the promoter region of this gene. The induced antigen was processed and presented properly for recognition by H-2L(d)-restricted P1A-specific CTLs. The combination of a demethylating agent and adoptive transfer of P1A-specific CTL effectively treated lung metastases in syngeneic mice challenged with P1A-negative 4T1 mammary carcinoma cells. These data show a novel strategy of combined chemoimmunotherapy of cancer targeting a CTA induced de novo in a broad range of tumor histologies, and support further evaluation of chromatin-remodeling agents for human cancer therapy.
Variation Of Bronchial Hyperresponsiveness According To Age and Gender In Pediatric Population
Authors: Young Ho Kim, Eun Lee, Song I. Yang, Young Ho Jung, Hyung Young Kim, Ju-Hee Seo, Byoung-Ju Kim, Hyo-Bin Kim, So Yeon Lee, Dae Jin Song, Woo Kyung Kim, Gwang Cheon Jang, Jung Yeon Shim, Jinho Yu, Soo-Jong Hong, Ji-Won Kwon
Journal: Journal of Allergy and Clinical Immunology (2014)
Towards individualised medicine for airways disease: identifying clinical phenotype groups: Figure 1–
Authors: J. Travers, M. Weatherall, J. Fingleton, R. Beasley
Journal: European Respiratory Journal (2012)

Towards individualised medicine for airways disease: identifying clinical phenotype groupsTo the Editors:Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases [1,2].In diagnosing a patient with asthma or COPD, an individual is thereby lumped together with other patients whose disease phenotype and response to treatment may be quite different.Doing so simplifies treatment guidelines and facilitates the application of evidence-based medicine but there is a risk that interventions that could provide benefit to certain disease subgroups are overlooked.At present, it is not known to what degree splitting of airways disease groups can lead to improved health outcomes and this question remains a focus of intense research.The approach in recent years has been to re-examine the classification of airways disease to identify disease subgroups that may respond to treatments in different ways.
SNAI transcription factors mediate epithelial-mesenchymal transition in lung fibrosis
Authors: A Jayachandran, M Konigshoff, H Yu, E Rupniewska, M Hecker, W Klepetko, W Seeger, O Eickelberg
Journal: Thorax (2009)

<h3>Background:</h3> Idiopathic pulmonary fibrosis (IPF) is a fatal interstitial lung disease characterised by accumulation of activated (myo)fibroblasts and excessive extracellular matrix deposition. The enhanced accumulation of (myo)fibroblasts may be attributed, in part, to the process of transforming growth factor β1 (TGFβ1)-induced epithelial–mesenchymal transition (EMT), the phenotypic switching of epithelial to fibroblast-like cells. Although alveolar epithelial type II (ATII) cells have been shown to undergo EMT, the precise mediators and mechanisms remain to be resolved. The objective of this study is to investigate the role of SNAI transcription factors in the process of EMT and in IPF. <h3>Methods:</h3> Using quantitative reverse transcription-PCR (RT-PCR), immunofluorescence, immunohistochemistry, western blotting, as well as gain- and loss-of-function studies and functional assays, the role of SNAI1 and SNAI2 in TGFβ1-induced EMT in ATII cells in vitro was assessed; and the expression of SNAI transcription factors was analysed in experimental and human IPF in vivo. <h3>Results:</h3> TGFβ1 treatment increased the expression and nuclear accumulation of SNAI1 and SNAI2, in concert with induction of EMT in ATII cells. SNAI overexpression was sufficient to induce EMT, and small interfering RNA (siRNA)-mediated SNAI depletion attenuated TGFβ1-induced ATII cell migration and EMT. SNAI expression was elevated in experimental and human IPF and localised to hyperplastic ATII cells in vivo. <h3>Conclusions:</h3> The results demonstrate that TGFβ1-induced EMT in ATII cells is essentially controlled by the expression and nuclear translocation of SNAI transcription factors. Increased SNAI1 and SNAI2 expression in experimental and human IPF in vivo suggests that SNAI-mediated EMT may contribute to the fibroblast pool in idiopathic pulmonary fibrosis.
Interpretation of bronchograms and chest radiographs in patients with chronic sputum production.
Authors: D C Currie, J C Cooke, A D Morgan, I H Kerr, D Delany, B Strickland, P J Cole
Journal: Thorax (1987)

Bronchograms and plain chest radiographs of 27 patients with chronic sputum production were reported separately in random order and independently by two pulmonary radiologists to establish the diagnostic rate of each investigation and to assess interobserver variation. Both radiologists agreed on the presence of bronchiectasis on bronchography in 19 of 27 (70%) patients and in 94 of 448 (21%) bronchopulmonary segments. One radiologist only interpreted the films as showing bronchiectasis in a further two (7%) patients and 26 (6%) segments. There was more disagreement about the presence or absence of individual bronchographic abnormalities. Two main groups of patients with bronchiectasis were identified by bronchography: 11 with bronchiectasis alone and eight with bronchiectasis and bronchographic features suggestive of "chronic bronchitis". There was no clinical difference between these two groups. Plain chest radiographs were insensitive, being diagnostic (both radiologists agreeing) of bronchiectasis in only nine of 19 (47%) patients with definite bronchiectasis on bronchography.
Mortality From Brain Tumor and Other Causes in a Cohort of Petrochemical Workers
Authors: R J Waxweiler, V Alexander, S S Leffingwell, M Haring, J W Lloyd
Journal: JNCI Journal of the National Cancer Institute (1983)

To evaluate a suspected excess of deaths due to brain tumor (BT) among petrochemical workers, a retrospective cohort mortality study was conducted among 7,595 men ever employed at a plant in Texas City, Texas, between 1941 and 1977. Among hourly employees, overall mortality was lower than expected from U.S. national rates [standardized mortality ratio (SMR) = 79]. However, 19 BT deaths (International Classification of Diseases, seventh revision, codes 193, 223, and 237) among hourly employees were observed as against 9.6 expected (SMR = 198), and with extension of the analysis to include BT deaths occurring in 1978 and 1979, 22 deaths were observed versus 10.7 expected (SMR = 206). Fifteen years or more after being hired, 19 of these workers died from BT versus 7.2 expected (SMR = 263), and the standardized mortality ratios increased with duration of employment to 377 for hourly workers who had worked over 20 years. Although nonoccupational etiologies cannot be dismissed, these data suggest an occupational etiology for certain BT deaths in petrochemical workers.
Interleukin 1 acts on cultured human vascular endothelium to increase the adhesion of polymorphonuclear leukocytes, monocytes, and related leukocyte cell lines.
Authors: M P Bevilacqua, J S Pober, M E Wheeler, R S Cotran, M A Gimbrone
Journal: Journal of Clinical Investigation (1985)

Increased leukocyte adhesion to the endothelial lining of blood vessels is an essential event in inflammation and the pathogenesis of certain vascular diseases. We have studied the effect of interleukin 1 (IL-1), an inflammatory/immune mediator, on endothelial-leukocyte adhesion using quantitative in vitro assays. Selective pretreatment of cultured human umbilical vein endothelial monolayers with IL-1 (5 U/ml, 4 h) resulted in an 18.3 +/- 2.6-fold increase in human peripheral blood polymorphonuclear leukocyte (PMN) adhesion (mean +/- SEM, n = 16) and a 2.6 +/- 0.3-fold increase in monocyte adhesion (n = 7) over basal levels. IL-1-treated endothelial monolayers also supported increased adhesion of the promyelocytic cell line HL-60 and the monocytelike cell line U937 (33.0 +/- 6.0-fold, n = 6 and 4.9 +/- 0.5-fold, n = 15, respectively). In contrast, selective IL-1 pretreatment of leukocytes, or the addition of IL-1 during the adhesion assay, did not alter endothelial-leukocyte adhesion. Conditioned medium from IL-1-treated endothelial cultures also did not promote leukocyte adhesion to untreated monolayers. IL-1 induction of endothelial adhesivity was concentration dependent (maximum, 10 U/ml), time dependent (peak, 4-6 h), and reversible, was blocked by cycloheximide (10 micrograms/ml) or actinomycin D (5 micrograms/ml) but not by acetylsalicylic acid (100 microM), and occurred without detectable endothelial cell damage. IL-1 treatment of SV40-transformed human endothelial cells and dermal fibroblasts did not increase their adhesivity for leukocytes. These data suggest that IL-1 can act selectively on human vascular endothelium to increase its adhesivity for circulating blood leukocytes, and thus to localize leukocyte-vessel wall interactions at sites of inflammation in vivo.
Deletion analysis of BMI1 oncoprotein identifies its negative regulatory domain
Authors: Ajay K Yadav, Anagh A Sahasrabuddhe, Manjari Dimri, Prashant V Bommi, Rachana Sainger, Goberdhan P Dimri
Journal: Molecular Cancer (2010)

Abstract Background The polycomb group (PcG) protein BMI1 is an important regulator of development. Additionally, aberrant expression of BMI1 has been linked to cancer stem cell phenotype and oncogenesis. In particular, its overexpression has been found in several human malignancies including breast cancer. Despite its established role in stem cell maintenance, cancer and development, at present not much is known about the functional domains of BMI1 oncoprotein. In the present study, we carried out a deletion analysis of BMI1 to identify its negative regulatory domain. Results We report that deletion of the C-terminal domain of BMI1, which is rich in proline-serine (PS) residues and previously described as PEST-like domain, increased the stability of BMI1, and promoted its pro-oncogenic activities in human mammary epithelial cells (HMECs). Specifically, overexpression of a PS region deleted mutant of BMI1 increased proliferation of HMECs and promoted an epithelial-mesenchymal transition (EMT) phenotype in the HMECs. Furthermore, when compared to the wild type BMI1, exogenous expression of the mutant BMI1 led to a significant downregulation of p16INK4a and an efficient bypass of cellular senescence in human diploid fibroblasts. Conclusions In summary, our data suggest that the PS domain of BMI1 is involved in its stability and that it negatively regulates function of BMI1 oncoprotein. Our results also suggest that the PS domain of BMI1 could be targeted for the treatment of proliferative disorders such as cancer and aging.
Targeting BRCA1 Localization to Augment Breast Tumor Sensitivity to Poly(ADP-Ribose) Polymerase Inhibition
Authors: Eddy S. Yang, Somaira Nowsheen, Mohammad A. Rahman, Rebecca S. Cook, Fen Xia
Journal: Cancer Research (2012)

Abstract PARP inhibitors have gained recent attention due to their highly selective killing of BRCA1/2-mutated and DNA double-strand break (DSB) repair–deficient tumors. Unfortunately, the majority of sporadic breast cancers carry wild-type BRCA1/2 and are proficient in DSB repair. We and others have shown that BRCA1 is a nuclear/cytoplasm shuttling protein that is transiently exported from the nucleus to the cytosol upon various stimuli. Thus, we hypothesized that depletion of nuclear BRCA1 would compromise DSB repair and subsequently render sporadic tumors susceptible to PARP inhibition. Indeed, in human sporadic breast cancer cells with functional BRCA1 and proficient DSB repair, a transient nuclear depletion of BRCA1 and subsequent homologous recombination repair deficit was induced with either truncated BRCA1 or irradiation. This rendered these human sporadic breast cancer cells susceptible to PARP inhibition. These observations were confirmed genetically using mislocated BRCA1 mutants as well as in vivo in mice bearing breast tumor xenografts. These data support the potential strategy of targeting BRCA1 location to convert BRCA1-proficient sporadic tumors to be susceptible to the synthetic lethal combination with PARP inhibitors. Cancer Res; 72(21); 5547–55. ©2012 AACR.
The Fgl2/fibroleukin prothrombinase contributes to immunologically mediated thrombosis in experimental and human viral hepatitis
Authors: Philip A. Marsden, Qin Ning, Laisum S. Fung, Xioping Luo, Yue Chen, Michael Mendicino, Anand Ghanekar, Jeremy A. Scott, Teresa Miller, Camie W.Y. Chan, Mathew W.C. Chan, Wei He, Reginald M. Gorczynski, David R. Grant, David A. Clark, M. James Phillips, Gary A. Levy
Journal: Journal of Clinical Investigation (2003)

Fibrin deposition and thrombosis within the microvasculature is now appreciated to play a pivotal role in the hepatocellular injury observed in experimental and human viral hepatitis. Importantly, the pathways by which fibrin generation is elicited in viral hepatitis may be mechanistically distinct from the classical pathways of coagulation induced by mechanical trauma or bacterial lipopolysaccharide (LPS). In the setting of murine hepatitis virus strain-3 (MHV-3) infection, a member of the Coronaviridae, activated endothelial cells and macrophages express distinct cell-surface procoagulants, including a novel prothrombinase, Fgl2/fibroleukin, which are important for both the initiation and localization of fibrin deposition. To assess the role of Fgl2/fibroleukin in murine viral hepatitis we generated a Fgl2/fibroleukin-deficient mouse. Peritoneal macrophages isolated from Fgl2/fibroleukin-/- mice did not generate a procoagulant response when infected with MHV-3. Fibrin deposition and liver necrosis were markedly reduced, and survival was increased in mice infected with MHV-3. To address the relevance of Fgl2/fibroleukin in human chronic viral hepatitis we studied patients with minimal and marked chronic hepatitis B. We detected robust expression of Fgl2/fibroleukin mRNA transcripts and protein in liver tissue isolated from patients with marked chronic hepatitis B. Fibrin deposition was strongly associated with Fgl2/fibroleukin expression. Collectively, these data indicate a critical role for Fgl2/fibroleukin in the pathophysiology of experimental and human viral hepatitis.