tbuckley/cabot-search huggingface dataset:
Androgen Receptor and Invasion in Prostate Cancer
Authors: Takahito Hara, Hideyo Miyazaki, Aram Lee, Chau P. Tran, Robert E. Reiter
Journal: Cancer Research (2008)

Abstract Activation of androgen receptor (AR) stimulates the growth of not only androgen-dependent but also of androgen-refractory prostate cancer. However, neither the role of AR in invasion/metastasis nor the relationship between invasiveness and androgen-refractory status has been established. In this study, we used the androgen-dependent prostate cancer cell line MDA PCa 2b, derived from a human bone metastasis, to generate an invasive subline (MDA-I) using a Matrigel chamber. MDA-I cells expressed higher levels of AR and prostate-specific antigen than their less invasive parental cells. Blocking AR function or removal of androgen suppressed the invasion of MDA-I cells, whereas stimulating AR increased invasion. In addition, forced AR overexpression increased the invasiveness of MDA PCa 2b cells. Next, we showed that an androgen-refractory subline (MDA-hr) of MDA PCa 2b cells also expressed higher levels of AR and were more invasive than their parental androgen-dependent cells. Blocking AR function suppressed the invasiveness of MDA-hr cells. Gelatin zymography indicated that matrix metalloproteinase 2 (MMP-2) and MMP-9 activities were regulated by AR signaling and closely correlated with the invasiveness of the androgen-dependent and androgen-refractory prostate cancer cells. These data suggest that AR promotes the invasiveness of both androgen-dependent and androgen-refractory prostate cancer and that a more invasive phenotype might develop through AR activation during cancer progression. These findings potentially support the use of adjuvant hormonal therapy and the future development of more potent androgen blockade therapy. [Cancer Res 2008;68(4):1128–35]
Neural Correlates of Traumatic Memories in Posttraumatic Stress Disorder: A Functional MRI Investigation
Authors: R A Lanius, P C Williamson, M Densmore, K Boksman, M A Gupta, R W Neufeld, J S Gati, R S Menon
Journal: American Journal of Psychiatry (2001)

The neuronal circuitry underlying posttraumatic stress disorder (PTSD) was studied in traumatized subjects with and without PTSD.Traumatized subjects with (N=9) and without (N=9) PTSD were studied by using the script-driven symptom provocation paradigm adapted to functional magnetic resonance imaging at a 4-T field strength.PTSD subjects showed significantly less activation of the thalamus, the anterior cingulate gyrus (Brodmann's area 32), and the medial frontal gyrus (Brodmann's area 10/11) than did the comparison subjects.The findings suggest anterior cingulate, frontal, and thalamic involvement in the neuronal circuitry underlying PTSD.
Prognostic Value of a Normal or Nonspecific Initial Electrocardiogram in Acute Myocardial Infarction
Authors: R D Welch, R J Zalenski, P D Frederick, J A Malmgren, S Compton, M Grzybowski, S Thomas, T Kowalenko, N R Every
Journal: JAMA (2001)

ContextAlthough previous studies have suggested that normal and nonspecific initial electrocardiograms (ECGs) are associated with a favorable prognosis for patients with acute myocardial infarction (AMI), their independent predictive value for mortality has not been examined.ObjectiveTo compare in-hospital mortality among patients with AMI who have normal or nonspecific initial ECGs with that of patients who have diagnostic ECGs.Design, Setting, and PatientsMultihospital observational study in which 391 208 patients with AMI met the study criteria between June 1994 and June 2000 and had ECGs that were normal (n = 30 759), nonspecific (n = 137 574), or diagnostic (n = 222 875; defined as ST-segment elevation or depression and/or left bundle-branch block). A logistic regression model was constructed using a propensity score for ECG findings and data on demographics, medical history, diagnostic procedures, and therapy to determine the independent prognostic value of a normal or nonspecific initial ECG.Main Outcome MeasuresIn-hospital mortality; composite outcome of in-hospital death and life-threatening adverse events.ResultsIn-hospital mortality rates were 5.7%, 8.7%, and 11.5% while the rates of the composite of mortality and life-threatening adverse events were 19.2%, 27.5%, and 34.9% for the normal, nonspecific, and diagnostic ECG groups, respectively. After adjusting for other predictor variables, the odds of mortality for the normal ECG group was 0.59 (95% confidence interval [CI], 0.56-0.63; P<.001) and for the nonspecific group was 0.70 (95% CI, 0.68-0.72; P<.001), compared with the diagnostic ECG group.ConclusionIn this large cohort of patients with AMI, patients presenting with normal or nonspecific ECGs did have lower in-hospital mortality rates than those of patients with diagnostic ECGs, yet the absolute rates were still unexpectedly high.
White Blood Cells Count and Incidence of Type 2 Diabetes in Young Men
Authors: Gilad Twig, Arnon Afek, Ari Shamiss, Estela Derazne, Dorit Tzur, Barak Gordon, Amir Tirosh
Journal: Diabetes Care (2012)

OBJECTIVE Association between white blood cell (WBC) count and diabetes risk has been recently suggested. We assessed whether WBC count is an independent risk factor for diabetes incidence among young healthy adults. RESEARCH DESIGN AND METHODS WBC count was measured in 24,897 young (mean age 30.8 ± 5.36 years), normoglycemic men with WBC range of 3,000 to 12,000 cells/mm3. Participants were periodically screened for diabetes during a mean follow-up of 7.5 years. RESULTS During 185,354 person-years of follow-up, diabetes was diagnosed in 447 subjects. A multivariate model adjusted for age, BMI, family history of diabetes, physical activity, and fasting glucose and triglyceride levels revealed a 7.6% increase in incident diabetes for every increment of 1,000 cells/mm3 (P = 0.046). When grouped in quintiles, a baseline WBC count above 6,900 cells/mm3 had an independent 52% increase in diabetes risk (hazard ratio 1.52 [95% CI 1.06–2.18]) compared with the lowest quintile (WBC &amp;lt;5,400 cells/mm3). Men at the lowest WBC quintile were protected from diabetes incidence even in the presence of overweight, family history of diabetes, or elevated triglyceride levels. After simultaneous control for risk factors, BMI was the primary contributor of the variation in multivariate models (P &amp;lt; 0.001), followed by age and WBC count (P &amp;lt; 0.001), and family history of diabetes and triglyceride levels (P = 0.12). CONCLUSIONS WBC count, a commonly used and widely available test, is an independent risk factor for diabetes in young men at values well within the normal range.
RESULTS OF THE INTRATRACHEAL INJECTION OF THE BORDET-GENGOU BACILLUS IN THE MONKEY AND RABBIT
Authors: Douglas H. Sprunt, Donald S. Martin, Sara McDearman
Journal: The Journal of Experimental Medicine (1938)

Experiments are reported which show that the virulent Bordet-Gengou bacillus can produce a significant lymphocytosis and an interstitial mononuclear pneumonia in both the monkey and the rabbit. Both of these reactions occur apparently as the result of a toxic material formed in vivo from the Bordet-Gengou bacillus and are not dependent on the multiplication of the organism itself. It was also shown that the strictly avirulent form could also cause an interstitial mononuclear pneumonia but no lymphocytosis. This interstitial mononuclear pneumonia was thought to be the result of the foreign substance produced by the organism when it was in this stage. This was substantiated by the fact that this lesion could be produced both by living and dead organisms.
Docetaxel Plus Prednisone or Mitoxantrone Plus Prednisone for Advanced Prostate Cancer: Updated Survival in the TAX 327 Study
Authors: Dominik R. Berthold, Gregory R. Pond, Freidele Soban, Ronald de Wit, Mario Eisenberger, Ian F. Tannock
Journal: Journal of Clinical Oncology (2008)

Purpose The TAX 327 study compared docetaxel administered every 3 weeks (D3), weekly docetaxel (D1), and mitoxantrone (M), each with prednisone (P), in 1,006 men with metastatic hormone-resistant prostate cancer (HRPC). The original analysis, undertaken in August 2003 when 557 deaths had occurred, showed significantly better survival and response rates for pain, prostate-specific antigen (PSA), and quality of life for D3P when compared with MP. Here, we report an updated analysis of survival. Methods Investigators were asked to provide the date of death or last follow-up for all participants who were alive in August 2003. Results By March 2007, data on 310 additional deaths were obtained (total = 867 deaths). The survival benefit of D3P compared with MP has persisted with extended follow-up (P = .004). Median survival time was 19.2 months (95% CI, 17.5 to 21.3 months) in the D3P arm, 17.8 months (95% CI, 16.2 to 19.2 months) in the D1P arm, and 16.3 months (95% CI, 14.3 to 17.9 months) in the MP arm. More patients survived ≥ 3 years in the D3P and D1P arms (18.6% and 16.6%, respectively) compared with the MP arm (13.5%). Similar trends in survival between treatment arms were seen for men greater than and less than 65 years of age, for those with and without pain at baseline, and for those with baseline PSA greater than and less than the median value of 115 ng/mL. Conclusion The present analysis confirms that survival of men with metastatic HRPC is significantly longer after treatment with D3P than with MP. Consistent results are observed across subgroups of patients.
Surgical repair of tricuspid atresia
Authors: F. Fontan, E. Baudet
Journal: Thorax (1971)

Surgical repair of tricuspid atresia has been carried out in three patients; two of these operations have been successful. A new surgical procedure has been used which transmits the whole vena caval blood to the lungs, while only oxygenated blood returns to the left heart. The right atrium is, in this way, `ventriclized9, to direct the inferior vena caval blood to the left lung, the right pulmonary artery receiving the superior vena caval blood through a cava-pulmonary anastomosis. This technique depends on the size of the pulmonary arteries, which must be large enough and at sufficiently low pressure to allow a cava-pulmonary anastomosis. The indications for this procedure apply only to children sufficiently well developed. Younger children or those whose pulmonary arteries are too small should be treated by palliative surgical procedures.
Pulmonary Function Tests in Preschool Children with Asthma
Authors: Nicole Beydon, Isabelle Pin, Régis Matran, Michèle Chaussain, Michèle Boulé, Beurey Alain, Mireille Bellet, Francis Amsallem, Corinne Alberti, André Denjean, Claude Gaultier
Journal: American Journal of Respiratory and Critical Care Medicine (2003)

Pulmonary function tests are seldom performed in preschool children with asthma. The aim of this multicenter study was to compare pulmonary function in 74 preschool children with asthma (height of 90-130 cm) and 84 healthy control subjects. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (interrupter technique) were measured. As compared with control children, children with asthma had a significantly higher resistance (0.77 +/- 0.20 vs. 0.92 +/- 0.22 kPa. L-1. second, p < 0.001) and significantly lower specific expiratory interrupter conductance (p < 0.005) values. Resistance values were significantly higher in children with asthma with than without symptoms on exertion (p < 0.05). The effect of bronchodilator administration, expressed as the percentage of baseline and predicted resistance values, was significantly greater in children with asthma than in control subjects (-18.6 +/- 13.6% vs. -11.2 +/- 15.2%, p </= 0.001, and -23.2 +/- 19.2% vs. -12.6 +/- 17.8%, p < 0.001), respectively. A 35% decrease in resistance after bronchodilation expressed as the percentage of predicted values had a likelihood ratio of 3 for separating the bronchodilator response in children with asthma from that in healthy control subjects. Pulmonary function tests that do not require active cooperation may help in the management and follow-up of preschool children with asthma who are unable to perform forced expiratory maneuvers.
Effect of albendazole treatments on the prevalence of atopy in children living in communities endemic for geohelminth parasites: a cluster-randomised trial
Authors: Philip J Cooper, Martha E Chico, Maritza G Vaca, Ana-Lucia Moncayo, J Martin Bland, Evelin Mafla, Fernanda Sanchez, Laura C Rodrigues, David P Strachan, George E Griffin
Journal: The Lancet (2006)
HLA-DRB1*04/*13 alleles are associated with vascular disease and antiphospholipid antibodies in systemic lupus erythematosus
Authors: Emeli Lundström, Johanna T Gustafsson, Andreas Jönsen, Dag Leonard, Agneta Zickert, Kerstin Elvin, Gunnar Sturfelt, Gunnel Nordmark, Anders A Bengtsson, Ulf Sundin, Henrik Källberg, Johanna K Sandling, Ann-Christine Syvänen, Lars Klareskog, Iva Gunnarsson, Lars Rönnblom, Leonid Padyukov, Elisabet Svenungsson
Journal: Annals of the Rheumatic Diseases (2012)

Background and objectives Vascular disease is common in systemic lupus erythematosus (SLE) and patients with antiphospholipid antibodies (aPL) are at high risk to develop arterial and venous thrombosis. Since HLA class II genotypes have been linked to the presence of pro-thrombotic aPL, we investigated the relationship between HLA-DRB1 alleles, aPL and vascular events in SLE patients. Methods 665 SLE patients of Caucasian origin and 1403 controls were included. Previous manifestations of ischaemic heart disease, ischaemic cerebrovascular disease (ICVD) and venous thromboembolism (together referred to as any vascular events (AVE)) were tabulated. aPL were measured with ELISA. Two-digit HLA-DRB1 typing was performed by sequence-specific primer-PCR. Results HLA-DRB1*04 was more frequent among SLE patients with ICVD compared to unaffected patients. This association remained after adjustment for known traditional cardiovascular risk factors. HLA-DRB1*13 was associated with AVE. All measured specificities of aPL—cardiolipin IgG and IgM, β 2 -glycoprotein-1 IgG, prothrombin (PT) IgG and a positive lupus anticoagulant test were associated with HLA-DRB1*04—while HLA-DRB1*13 was associated with IgG antibodies (β 2 -glycoprotein-1, cardiolipin and PT). In patients with the combined risk alleles, HLA-DRB1*04/*13, there was a significant additive interaction for the outcomes AVE and ICVD. Conclusions The HLA-DRB1*04 and HLA-DRB1*13 alleles are associated with vascular events and an aPL positive immune-phenotype in SLE. Results demonstrate that a subset of SLE patients is genetically disposed to vascular vulnerability.
Studies with Radioactive Endotoxin. I. The Use of Cr51 to Label Endotoxin of Escherichia Coli1
Authors: A. I. Braude, F. J. Carey, Donald Sutherland, Margaret Zalesky
Journal: Journal of Clinical Investigation (1955)

The endotoxins in different species of gram negative bacteria exhibit remarkably similar bio- logic effects which have been observed in both ex- perimental animals and'man (1-5).These effects may be seen after the injection of living bacteria," killed bacteria, or endotoxin itself; they consist of fever, shock, leukocytosis preceded by leuko- penia, hypoglycemia, diarrhea, and prostration..Although there are sometimes hemorrhages in the intestine and other viscera, the findings post- mortem are not enough to explain the cause of death or to indicate where the endotoxin acts.As a means of locating the site of action of en- dotoxin, as well as its fate in tivo, a series of ex- periments have been carried out using endotoxin labelled with radioactive chromium.The endo- toxin of Escherichia coli was selected for this study because it can be conveniently prepared in large quantities without the hazards associated with more highly pathogenic bacteria.Radioactive chromium proved to be satisfactory by virtue of its firm attachment to endotoxin, its relative safety in handling, and its half-life of 26.5 days.This report deals with the technique of labelling of E. coli endotoxin and with the properties of labelled toxin; those which follow describe its distribution in vivo under various experimental conditions. EXPERIMENTAL METHODS I. Preparation of E. coli EndotoxinThe method of preparation of E. coli endotoxin was based on Boivmi and Mesrobeanu's (6) principle that endotoxin can be extracted by trichloroacetic acid at cold temperatures.The bacteria were grown in a synthetic medium modified from that described by Gladstone (7) for growth of S. typhosa.For the preparation of 25 liters, the following constituents were used: KH2PO.X This investigation was supported in part by the Re- search and Development Division, Office of
Lung Fibroblast Repair Functions in Patients with Chronic Obstructive Pulmonary Disease Are Altered by Multiple Mechanisms
Authors: Shinsaku Togo, Olaf Holz, Xiangde Liu, Hisatoshi Sugiura, Koichiro Kamio, Xiangqi Wang, Shin Kawasaki, Youngsoo Ahn, Karin Fredriksson, C. Magnus Skold, Kai Christian Mueller, Detlef Branscheid, Lutz Welker, Henrik Watz, Helgo Magnussen, Stephen I. Rennard
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

Fibroblasts are believed to be the major cells responsible for the production and maintenance of extracellular matrix. Alterations in fibroblast functional capacity, therefore, could play a role in the pathogenesis of pulmonary emphysema, which is characterized by inadequate maintenance of tissue structure.
Interpreting Improvement in Expiratory Flows after Lung Volume Reduction Surgery in Terms of Flow Limitation Theory
Authors: EDWARD P. INGENITO, STEPHEN H. LORING, MARILYN L. MOY, STEVEN J. MENTZER, SCOTT J. SWANSON, JOHN J. REILLY
Journal: American Journal of Respiratory and Critical Care Medicine (2001)

Spirometry and pulmonary mechanics were measured pre- and postoperatively in 37 patients undergoing bilateral lung volume reduction surgery (LVRS). The relative contributions of changes in compliance (Cl), recoil pressures (Ptlc), small airway conductance (Gu), and airway closing pressures (Ptm ′ ) to changes in expiratory flows were examined with a Taylor series expansion of the Pride– Permutt model of flow limitation. The resulting variational expression, δV˙max = Gu δ Pel + Pel δ Gu − Gu δ Ptm ′ − Ptm ′δ Gu − δ Gu δ Ptm ′ , was then used to describe how the peak flow rate (V˙max) depends on preoperative Gu, P tlc, Ptm ′ , and on changes ( δ ) in these parameters after surgery. After LVRS, both FEV1 and V˙max increased significantly ( Δ FEV1 = 28 ± 44%; ΔV˙max = 78 ± 132%), and changes in FEV1 and V˙max correlated closely (r = 0.74, p < 0.001). Among responders ( Δ FEV1 ⩾ 12%; n = 19; Δ FEV1 = 60 ± 38%), Ptlc increased (8.8 ± 2.8 to 12.2 ± 4.7 cm H2O) and the time constant for expiration ( τ = Cl/Gu) decreased (2.67 ± 0.62 to 2.35 ± 0.55 s), while Ptm ′ , Cl, and Gu did not change. Gu δ Pel, the change in recoil weighted by preoperative conductance upstream of the flow-limiting site, accounted for 72% of the improvement in V˙max. Among nonresponders ( Δ FEV1 = − 6 ± 15%, n = 18), τ increased significantly, contributing to a decline in FEV1/FVC ratio. Pel δ Gu decreased ( − 0.25 ± 0.68, p = 0.013), accounting for all of the decline in V˙max. This analysis suggests that ( 1) improvement in expiratory flows after LVRS is largely due to increases in recoil pressure; (2) large improvements in FEV1 can occur without changes in Gu or Ptm ′ , arguing that LVRS has little effect on airway resistance or closure; and (3) large changes in Ptlc can occur without changes in Cl, supporting arguments of Fessler and Permutt (Am J Respir Crit Care Med 1998;157:715–722) that “resizing of the lung to chest wall” is the primary mechanism by which LVRS improves lung function.
Failure of Phenoxybenzamine to Prevent Formation of Hepatomas After Chronic Carbon Tetrachloride Administration<xref ref-type="fn" rid="FN2">2</xref>
Authors: Glenn F. Kiplinger, Charles J. Kensler
Journal: JNCI Journal of the National Cancer Institute (1963)

Several pharmacological agents affecting the response of animals to the sympathetic neurohumors, epinephrine and levarterenol, were screened for their ability to prevent acute hepatic damage due to carbon tetrachloride (CCl4) in C3H mice. The vasodilator, mannitol hexanitrate, was ineffective as was the adrenergic blocking agent, ergotamine. Ephedrine potentiated the acute hepatotoxic effects of CCl4. Phenoxybenzamine (Dibenzyline) and reserpine were effective in reducing the hepatotoxicity of CCl4. Phenoxybenzamine was chosen for use in a chronic experiment designed to demonstrate whether adrenergic blockade with this agent would prevent the formation of hepatomas in C3H mice chronically treated with CCl4. At the doses tested there was no evidence of protection against hepatoma formation.—J Nat Cancer Inst 30: 837–843, 1963.
Toll-like receptor-mediated, enhanced production of profibrotic TIMP-1 in monocytes from patients with systemic sclerosis: role of serum factors
Authors: Marzena Ciechomska, Christiaan A Huigens, Thomas Hügle, Tess Stanly, Andreas Gessner, Bridget Griffiths, Timothy R D J Radstake, Sophie Hambleton, Steven O'Reilly, Jacob M van Laar
Journal: Annals of the Rheumatic Diseases (2012)

<h3>Objectives</h3> To investigate whether monocytes contribute to matrix deposition in systemic sclerosis (SSc) by production of tissue-inhibitor of metalloproteinase-1 (TIMP-1). <h3>Methods</h3> Matrix metalloproteinase-1 (MMP-1) and TIMP-1 expression and secretion were measured by qRT-PCR and ELISA in circulating monocytes from patients with SSc, patients with rheumatoid arthritis (RA) and healthy controls (HC) and in healthy monocytes cultured in the presence of SSc or HC serum samples. Production of TIMP-1 was determined in response to a panel of Toll-like receptor (TLR) agonists and MyD88 inhibitory peptide. The functional effect of conditioned media from SSc and HC serum samples or TLR8-stimulated monocytes was studied in an MMP-1 activity assay. <h3>Results</h3> TIMP-1 production by monocytes was upregulated in patients with SSc compared with patients with RA and HC. Incubation of HC monocytes with SSc serum samples resulted in functionally active TIMP-1 production. However, pretreatment with MyD88 inhibitor, but not control peptide, decreased TIMP-1 secretion. TIMP-1 production was significantly stronger when SSc and HC monocytes were stimulated with TLR8 (ssRNA) agonist, but the response was more pronounced in SSc monocytes. TIMP-1 production after TLR stimulation was also strongly reduced in the presence of MyD88 inhibitory peptide or in the monocytes isolated from a patient with a genetic TLR signalling defect. MMP-1 activity was significantly inhibited in media from serum samples or TLR8-stimulated monocytes indicative of functional TIMP activity. <h3>Conclusions</h3> This study demonstrates profibrotic properties of circulating monocytes from patients with SSc and a key role for TLR signalling, particularly TLR8, in TIMP-1 secretion and matrix remodelling.