tbuckley/cabot-search huggingface dataset:
Polymorphism of the NADH/NADPH Oxidase <i>p22 phox</i> Gene in Patients With Coronary Artery Disease
Authors: Nobutaka Inoue, Seinosuke Kawashima, Kenji Kanazawa, Shinichiro Yamada, Hozuka Akita, Mitsuhiro Yokoyama
Journal: Circulation (1998)

Oxidative stress in the vasculature has been implicated in the pathogenesis of coronary artery disease (CAD). NADH/NADPH oxidase is a key enzyme of superoxide production in the vasculature. p22 phox, an essential component of NADH/NADPH oxidase, has four types of polymorphism. The C242T polymorphism changes histidine-72 to tyrosine, located in the potential heme-binding sites, whereas A640G polymorphism is located in the 3' untranslated region.We investigated whether these polymorphisms were associated with risk of CAD by use of restriction fragment length polymorphism (RFLP). The prevalence of the TC + TT genotype of the C242T polymorphism was significantly more frequent in control subjects (n=201) than in the patients with CAD (n=201). The odds ratio of the TC + TT versus CC genotype of the C242T polymorphism between control subjects and case patients was 0.49 (95% CI, 0.28 to 0.87) (P=.015). The prevalence of the genotypes of the A640G polymorphism was not different between groups. The association of C242T polymorphism of the p22 phox gene with CAD was statistically significant and independent of other risk factors.The mutation of the potential heme-binding site of the p22 phox gene may reduce susceptibility to CAD. Our observations suggest that the C242T polymorphism of the p22 phox gene is a novel genetic marker that has a protective effect on coronary risk.
Timp3 deficiency in insulin receptor-haploinsufficient mice promotes diabetes and vascular inflammation via increased TNF- 
Authors: M. Federici
Journal: Journal of Clinical Investigation (2005)

Activation of inflammatory pathways may contribute to the beginning and the progression of both atherosclerosis and type 2 diabetes. Here we report a novel interaction between insulin action and control of inflammation, resulting in glucose intolerance and vascular inflammation and amenable to therapeutic modulation. In insulin receptor heterozygous (Insr+/-) mice, we identified the deficiency of tissue inhibitor of metalloproteinase 3 (Timp3, an inhibitor of both TNF-alpha-converting enzyme [TACE] and MMPs) as a common bond between glucose intolerance and vascular inflammation. Among Insr+/- mice, those that develop diabetes have reduced Timp3 and increased TACE activity. Unchecked TACE activity causes an increase in levels of soluble TNF-alpha, which subsequently promotes diabetes and vascular inflammation. Double heterozygous Insr+/-Timp3+/- mice develop mild hyperglycemia and hyperinsulinemia at 3 months and overt glucose intolerance and hyperinsulinemia at 6 months. A therapeutic role for Timp3/TACE modulation is supported by the observation that pharmacological inhibition of TACE led to marked reduction of hyperglycemia and vascular inflammation in Insr+/- diabetic mice, as well as by the observation of increased insulin sensitivity in Tace+/- mice compared with WT mice. Our results suggest that an interplay between reduced insulin action and unchecked TACE activity promotes diabetes and vascular inflammation.
Rosiglitazone Facilitates Angiogenic Progenitor Cell Differentiation Toward Endothelial Lineage
Authors: Chao-Hung Wang, Nadia Ciliberti, Shu-Hong Li, Paul E. Szmitko, Richard D. Weisel, Paul W.M. Fedak, Mohammed Al-Omran, Wen-Jin Cherng, Ren-Ke Li, William L. Stanford, Subodh Verma
Journal: Circulation (2004)

Peroxisome proliferator-activated receptor-gamma (PPAR-gamma) agonists inhibit vascular smooth muscle proliferation and migration and improve endothelial function. It is unknown whether PPAR-gamma agonists favorably modulate bone marrow (BM)-derived angiogenic progenitor cells (APCs) to promote endothelial lineage differentiation and early reendothelialization after vascular intervention.C57/BL6 mice, treated with or without rosiglitazone (8 mg/kg per day), a PPAR-gamma agonist, underwent femoral angioplasty. Rosiglitazone treatment attenuated neointimal formation (intima/media ratio: 0.98+/-0.12 [rosiglitazone] versus 3.1+/-0.5 [control]; P<0.001; n=10 per group). Using a BM transplantation model, we identified that 58+/-12% of the cells within the neointima at 4 weeks were derived from the BM. Pure endothelial marker-positive, pure alpha-smooth muscle actin (alphaSMA)-positive, or double-positive APCs could be found both in mouse BM and in human peripheral blood after culture in conditional medium enriched with vascular endothelial growth factor. Rosiglitazone caused a 6-fold (P<0.001) increase in colony formation by human endothelial progenitor cells, promoted the differentiation of APCs toward the endothelial lineage in mouse BM in vivo (0.66+/-0.06% [control] to 0.95+/-0.08% [rosiglitazone]; P<0.05) and in human peripheral blood in vitro (13.2+/-1.5% [control] to 28.4+/-3.3% [rosiglitazone]; P<0.05), and inhibited the differentiation toward the smooth muscle cell lineage. Within the neointima, rosiglitazone also stimulated APCs to differentiate into mature endothelial cells and caused earlier reendothelialization compared with controls (31+/-5 versus 8+/-2 CD31-positive cells per millimeter of neointimal surface on day 14; P<0.01).Similar to embryonic stem cell-derived progenitors, the adult BM and peripheral blood harbor APCs that are at least bipotential and able to differentiate into endothelial and smooth muscle lineages. The PPAR-gamma agonist rosiglitazone promotes the differentiation of these APCs toward the endothelial lineage and attenuates restenosis after angioplasty.
"I'm all right, John": voting patterns and mortality in England and Wales, 1981-92
Authors: G. D. Smith, D. Dorling
Journal: BMJ (1996)

To investigate the association between voting patterns, deprivation, and mortality across England and Wales.Ecological study.All the electoral constituencies of England and Wales.Combined and sex specific standardised mortality ratios.For the years surrounding the three elections of 1983, 1987, and 1992 overall standardised mortality ratios showed substantial negative correlations of -0.74 to -0.76 with Conservative voting and substantial positive correlations of 0.73 to 0.77 with Labour voting (all P < 0.0001). Correlations were higher for male than female mortality. Conservative voting was strongly negatively correlated (r = -0.84) with the Townsend deprivation score, while Labour voting was positively correlated (r = 0.74) with this. Labour and Conservative voting explained more of the variance in mortality than did the Townsend score. In multiple regression analyses for the 1992 election Labour voting (P < 0.0001), Conservative voting (P < 0.0001), the Townsend score (P = 0.016), and abstentions (P = 0.032) were all associated with mortality. Labour and conservative voting explained 61% of the variance in mortality between constituencies; when Townsend score and abstentions were added this increased to 63%.Conservative and Labour voting are at least as strongly associated with mortality as is a standard deprivation index. Voting patterns may add information above that provided by indicators of material deprivation. People living in better circumstances and who have better health, who are least likely to require unemployment benefit and free school meals or to rely on a state pension in old age, and who are most able to opt out of state subsidised provision of transport, education, and the NHS, vote for the party that is most likely to dismantle the welfare state.
Association of Foxp3 regulatory gene expression with graft-versus-host disease
Authors: Yuji Miura, Christopher J. Thoburn, Emilie C. Bright, Michele L. Phelps, Tahiro Shin, Elizabeth C. Matsui, William H. Matsui, Sally Arai, Ephraim J. Fuchs, Georgia B. Vogelsang, Richard J. Jones, Allan D. Hess
Journal: Blood (2004)
Prediagnosis Soy Food Consumption and Lung Cancer Survival in Women
Authors: Gong Yang, Xiao-Ou Shu, Hong-Lan Li, Wong-Ho Chow, Wanqing Wen, Yong-Bing Xiang, Xianglan Zhang, Hui Cai, Bu-Tian Ji, Yu-Tang Gao, Wei Zheng
Journal: Journal of Clinical Oncology (2013)

We recently reported an inverse association between soy food intake and lung cancer risk among nonsmoking women. The effect size for aggressive lung cancers was larger than that observed for other types of lung cancer. Therefore, we hypothesized that soy consumption may favorably affect the overall survival of patients with lung cancer.This analysis included 444 women with incident lung cancer identified from the Shanghai Women's Health Study. Prediagnosis soy food intake was assessed at enrollment and reassessed 2 years later. Proportional hazards models were used to evaluate the association between soy food intake and overall survival.Of the 444 patients with lung cancer, 318 died during follow-up. Initial analyses including all patients showed that higher intake of soy food was associated with better overall survival after adjusting for demographic and lifestyle characteristics and other nonclinical factors. Larger effect sizes for the association were found after additional adjustment for tumor stage and treatment in analyses including 301 patients with data available on these clinical factors. Compared with the median intake of soy food, fully adjusted hazard ratios for total mortality associated with the 10th, 30th, 70th, and 90th percentiles of intake were 1.81 (95% CI, 1.26 to 2.59), 1.25 (95% CI, 1.09 to 1.42), 0.88 (95% CI, 0.80 to 0.97), and 0.89 (95% CI, 0.68 to 1.16), respectively. Similar inverse associations were observed for dietary isoflavone intake.This study suggests, to the best of our knowledge for the first time, that, among women with lung cancer, prediagnosis intake of soy food is associated with better overall survival.
Specific targeting of human peripheral blood T cells by heteroaggregates containing anti-T3 crosslinked to anti-target cell antibodies.
Authors: P Perez, R W Hoffman, J A Titus, D M Segal
Journal: The Journal of Experimental Medicine (1986)

Antibody heteroaggregates have been used to render human peripheral blood T cells lytic for specified targets. The heteroaggregates contain anti-T3 covalently linked to antibodies against nominal target cell antigens. Such heteroaggregates bind target cells directly to T3 molecules on effector cells and trigger target cell lysis. Freshly prepared human PBL, when coated with anti-T3-containing heteroaggregates, are lytic without further stimulation, although brief exposure to crude lymphokine-containing supernatants or recombinant IL-2, but not recombinant IFN-gamma, enhances the activity. The effector cells are T8+, and when fully stimulated, their lytic activity approaches that of some cloned CTL. When T cells are treated with heteroaggregate, washed, and incubated at 37 degrees C in medium not containing heteroaggregate, they retain activity for at least 24 h. The results of this study suggest a strategy in which heteroaggregate-coated T cells could be used in vivo to mount a lytic response against pathogenic cells such as tumor cells or virus-infected cells.
Pediatric Oncology: Model Tumors of Unparalleled Import
Authors: M. A. Israel
Journal: JNCI Journal of the National Cancer Institute (1989)

Molecular studies of tumors arising during childhood have provided insights important for our understanding of the genetic and cellular events that now seem likely to mediate the development of many different malignancies. Of particular interest have been recent studies using recombinant DNA technology to study the pressure genetic alterations now thought to be central features of oncogenesis. Oncogenes and recessive cancer genes, first recognized to be of clinical importance during the study of Burkitt's lymphoma and retinoblastoma, are now thought to play a role in the development of most, if not all, tumors. Studies to identify more effective approaches to cancer prevention, detection, staging, and treatment are now seeking to build upon an understanding of those genetic alterations. It can be expected that pediatric oncology will once again play a pivotal role as these studies mature into clinical trials.
Increased bone formation and decreased osteocalcin expression induced by reduced Twist dosage in Saethre-Chotzen syndrome
Authors: M. Yousfi, F. Lasmoles, A. Lomri, P. Delannoy, P.J. Marie
Journal: Journal of Clinical Investigation (2001)

The Saethre-Chotzen syndrome is characterized by premature fusion of cranial sutures resulting from mutations in Twist, a basic helix-loop-helix (bHLH) transcription factor. We have identified Twist target genes using human mutant calvaria osteoblastic cells from a child with Saethre-Chotzen syndrome with a Twist mutation that introduces a stop codon upstream of the bHLH domain. We observed that Twist mRNA and protein levels were reduced in mutant cells and that the Twist mutation increased cell growth in mutant osteoblasts compared with control cells. The mutation also caused increased alkaline phosphatase and type I collagen expression independently of cell growth. During in vitro osteogenesis, Twist mutant cells showed increased ability to form alkaline phosphatase-positive bone-like nodular structures associated with increased type I collagen expression. Mutant cells also showed increased collagen synthesis and matrix production when cultured in aggregates, as well as an increased capacity to form a collagenous matrix in vivo when transplanted into nude mice. In contrast, Twist mutant osteoblasts displayed a cell-autonomous reduction of osteocalcin mRNA expression in basal conditions and during osteogenesis. The data show that genetic deletion of Twist causing reduced Twist dosage increases cell growth, collagen expression, and osteogenic capability, but inhibits osteocalcin gene expression. This provides one mechanism that may contribute to the premature cranial ossification induced by deletion of the bHLH Twist domain in Saethre-Chotzen syndrome.
Safety and immunogenicity of a Vero-cell-derived, inactivated Japanese encephalitis vaccine: a non-inferiority, phase III, randomised controlled trial
Authors: E Tauber, H Kollaritsch, M Korinek, P Rendi-Wagner, B Jilma, C Firbas, S Schranz, E Jong, A Klingler, S Dewasthaly, CS Klade
Journal: The Lancet (2007)
A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer
Authors: J.A. Ajani, L. Xiao, J.A. Roth, W.L. Hofstetter, G. Walsh, R. Komaki, Z. Liao, D.C. Rice, A.A. Vaporciyan, D.M. Maru, J.H. Lee, M.S. Bhutani, A. Eid, J.C. Yao, A.P. Phan, A. Halpin, A. Suzuki, T. Taketa, P.F. Thall, S.G. Swisher
Journal: Annals of Oncology (2013)
Does Loss of CD151 Expression Promote the Metastasis of Hypoxic Colon Cancer Cells?
Authors: Gregg L. Semenza
Journal: Clinical Cancer Research (2008)

Abstract Intratumoral hypoxia increases invasion and metastasis through multiple mechanisms, including changes in gene expression that are mediated by hypoxia-inducible factor 1. In hypoxic colon cancer cells, hypoxia-inducible factor 1 inhibits the expression of CD151, a cell surface molecule that normally tethers epithelial cells to the basement membrane, which may promote metastasis.
On-line monitoring of mixed venous oxygen saturation after cardiothoracic surgery.
Authors: X H Krauss, P D Verdouw, P G Hughenholtz, J Nauta
Journal: Thorax (1975)

On-line monitoring of MVo2 sat. in vivo by means of fibreoptic reflectometry was studied in 19 patients as to its predictive value during the postoperative course after thoracotomy for periods up to 60 hours. In all but one of the 10 patients with MVo2 sat. less than 65% for at least one hour complications occurred. A fall of MVo2 sat. of more than 5% or a value below 60% predicted a period of hypotension in six patients. In two of them this coincided with a period of ventricular arrhythmias. In those with MVo2 sat. greater than 65% no postoperative complications such as arrhythmias, shock, respiratory dysfunction or oliguria took place.
Limited validity of the American College of Rheumatology criteria for classifying patients with gout in primary care
Authors: Hein J E M Janssens, Mathijs Janssen, Eloy H van de Lisdonk, Jaap Fransen, Piet L C M van Riel, Chris van Weel
Journal: Annals of the Rheumatic Diseases (2009)

In order to classify gout without identification of monosodium urate (MSU) crystals, the American College of Rheumatology (ACR) formulated criteria in 1977.1 Of the 11 criteria, ≥6 have to be present to classify patients as having gout. The criteria were not developed with reference to MSU crystals, nor were they tested properly afterwards against this gold standard.1,–,3 However, as they are widely used and cited, testing their validity is critical to our ability to understand and treat gout.4

Many studies of gout include patients with ‘self-reported gout’, provided they fulfil the ACR criteria. Most self-reported diagnoses of gout will originate from a diagnosis made by a family physician as most patients presenting with acute gout are managed by them.2 5 This makes the primary care setting particularly relevant to test the ACR criteria.

We designed a prospective study in a Dutch primary care population (∼200 000 subjects) to estimate the validity of the ACR criteria (patient recruitment 2004–6). We used identified MSU …
<i>TP53</i> Disruptive Mutations Lead to Head and Neck Cancer Treatment Failure through Inhibition of Radiation-Induced Senescence
Authors: Heath D. Skinner, Vlad C. Sandulache, Thomas J. Ow, Raymond E. Meyn, John S. Yordy, Beth M. Beadle, Alison L. Fitzgerald, Uma Giri, K. Kian Ang, Jeffrey N. Myers
Journal: Clinical Cancer Research (2011)

Mortality of patients with head and neck squamous cell carcinoma (HNSCC) is primarily driven by tumor cell radioresistance leading to locoregional recurrence (LRR). In this study, we use a classification of TP53 mutation (disruptive vs. nondisruptive) and examine impact on clinical outcomes and radiation sensitivity.Seventy-four patients with HNSCC treated with surgery and postoperative radiation and 38 HNSCC cell lines were assembled; for each, TP53 was sequenced and the in vitro radioresistance measured using clonogenic assays. p53 protein expression was inhibited using short hairpin RNA (shRNA) and overexpressed using a retrovirus. Radiation-induced apoptosis, mitotic cell death, senescence, and reactive oxygen species (ROS) assays were carried out. The effect of the drug metformin on overcoming mutant p53-associated radiation resistance was examined in vitro as well as in vivo, using an orthotopic xenograft model.Mutant TP53 alone was not predictive of LRR; however, disruptive TP53 mutation strongly predicted LRR (P = 0.03). Cell lines with disruptive mutations were significantly more radioresistant (P < 0.05). Expression of disruptive TP53 mutations significantly decreased radiation-induced senescence, as measured by SA-β-gal staining, p21 expression, and release of ROS. The mitochondrial agent metformin potentiated the effects of radiation in the presence of a disruptive TP53 mutation partially via senescence. Examination of our patient cohort showed that LRR was decreased in patients taking metformin.Disruptive TP53 mutations in HNSCC tumors predicts for LRR, because of increased radioresistance via the inhibition of senescence. Metformin can serve as a radiosensitizer for HNSCC with disruptive TP53, presaging the possibility of personalizing HNSCC treatment.
THE RELATIVE LOSS OF HEAT AND WEIGHT IN THE NEWBORN, AND THE TREATMENT OF SHOCK
Authors: A. L. McIlroy
Journal: BMJ (1925)

t i M f f x T 67 (c) Dye tests have their valute in sur-gical p)ractice.In medical " cases they y-ield results comparable to, but not so iiiniformly reliable as, blood urea estim-atiols.
Stem Cell Factor Deficiency Is Vasculoprotective
Authors: Chao-Hung Wang, Nicole Anderson, Shu-Hong Li, Paul E. Szmitko, Wen-Jing Cherng, Paul W.M. Fedak, Shafie Fazel, Ren-Ke Li, Terrence M. Yau, Richard D. Weisel, William L. Stanford, Subodh Verma
Journal: Circulation Research (2006)

Evidence suggests that bone marrow (BM) cells may give rise to a significant proportion of smooth muscle cells (SMCs) that contribute to intimal hyperplasia after vascular injury; however, the molecular pathways involved and the timeline of these events remain poorly characterized. We hypothesized that the stem cell factor (SCF)/c-Kit tyrosine kinase signaling pathway is critical to neointimal formation by BM-derived progenitors. Wire-induced femoral artery injury in mice reconstituted with wild-type BM cells expressing yellow fluorescent protein was performed, which revealed that 66+/-12% of the SMCs (alpha-smooth muscle actin-positive [alphaSMA(+)] cells) in the neointima were from BM. To characterize the role of the SCF/c-Kit pathway, we used c-Kit deficient W/W(v) and SCF-deficient Steel-Dickie mice. Strikingly, vascular injury in these mice resulted in almost a complete inhibition of neointimal formation, whereas wild-type BM reconstitution of c-Kit mutant mice led to neointimal formation in a similar fashion as wild-type animals, as did chronic administration of SCF in matrix metalloproteinase-9-deficient mice, a model of soluble SCF deficiency. Pharmacological antagonism of the SCF/c-Kit pathway with imatinib mesylate (Gleevec) or ACK2 (c-Kit antibody) also resulted in a marked reduction in intimal hyperplasia. Vascular injury resulted in the local upregulation of SCF expression. c-Kit(+) progenitor cells (PCs) homed to the injured vascular wall and differentiated into alphaSMA(+) cells. Vascular injury also caused an increase in circulating SCF levels which promoted CD34(+) PC mobilization, a response that was blunted in mutant and imatinib mesylate-treated mice. In vitro, SCF promoted adhesion of BM PCs to fibronectin. Additionally, anti-SCF antibodies inhibited adhesion of BM PCs to activated SMCs and diminished SMC differentiation. These data indicate that SCF/c-Kit signaling plays a pivotal role in the development of neointima by BM-derived PCs and that the inhibition of this pathway may serve as a novel therapeutic target to limit aberrant vascular remodeling.
Overexpression of endoplasmic reticulum-resident chaperone attenuates cardiomyocyte death induced by proteasome inhibition
Authors: H. Y. Fu, T. Minamino, O. Tsukamoto, T. Sawada, M. Asai, H. Kato, Y. Asano, M. Fujita, S. Takashima, M. Hori, M. Kitakaze
Journal: Cardiovascular Research (2008)

Proteasome inhibitors are a novel class of anticancer agents that induce tumour cell death via endoplasmic reticulum (ER) stress. Since ER stress is involved in the development of heart failure, we investigated the role of ER-initiated cardiomyocyte death by proteasome inhibition.Rat neonatal cardiomyocytes were used in this study. Proteasome activity was assayed using proteasome peptidase substrates. Cell viability and apoptosis were measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenol tetrazolium bromide and flow cytometry, respectively. Western blot analysis, real-time polymerase chain reaction (PCR) and reverse transcriptional PCR were used to detect the expression of protein and messenger ribonucleic acid (RNA). The location of overexpressed glucose-regulated protein (GRP) 78 was observed by confocal fluorescence microscopy. Proteasome inhibition induced cardiomyocyte death and activated ER stress-induced transcriptional factor ATF6, but not XBP1 (X-box binding protein 1), without up-regulating ER chaperones. ER-initiated apoptosis signalling, including cytosine-cytosine-adenine-adenine-thymine enhancer-binding protein (C/EBP) homologous protein (CHOP), c-Jun-N-terminal kinase (JNK), and caspase-12, was activated by proteasome inhibition. Short interference RNA targeting CHOP, but not the blockage of caspase-12 or JNK pathway, attenuated cardiomyocyte death. Overexpression of GRP78 suppressed both CHOP expression and cardiomyocyte death by proteasome inhibition.These findings demonstrate that proteasome inhibition induces ER-initiated cardiomyocyte death via CHOP-dependent pathways without compensatory up-regulation of ER chaperones. Supplement and/or pharmacological induction of GRP78 can attenuate cardiac damage by proteasome inhibition.