tbuckley/cabot-search huggingface dataset:
Short term effect of oxygen on renal haemodynamics in patients with hypoxaemic chronic obstructive airways disease.
Authors: S V Baudouin, J Bott, A Ward, C Deane, J Moxham
Journal: Thorax (1992)

BACKGROUND: Oxygen therapy is effective in the prevention and treatment of oedematous exacerbations of cor pulmonale. As renal blood flow is reduced in cor pulmonale a study was designed to investigate whether one of the beneficial effects of oxygen was to increase renal blood flow. The effect of oxygen therapy on renal haemodynamics measured noninvasively was examined in patients with chronic obstructive airways disease and previous episodes of oedema. METHODS: Renal blood flow waveforms were recorded in a single vessel by colour flow Doppler ultrasound in nine hypoxaemic patients (PaO2) (arterial oxygen tension &lt; 8 kPa while they were breathing air) with chronic obstructive airways disease and previous oedema and eight age matched normoxaemic volunteers (arterial oxygen saturation (SaO2) 97% or more when breathing air) while they were breathing air and oxygen. SaO2 and transcutaneous PaO2 (TcPO2) and PaCO2 (TcPCO2) were monitored. Five renal velocity profile recordings were made from the same segmental vessel with the patient breathing room air for one hour followed by oxygen titrated to achieve an oxygen saturation of 95% or more without a rise in TcPCO2 for 15 minutes. Control subjects breathed 35% oxygen. RESULTS: No significant change in the pulsatility index (a measure of distal vascular resistance) or mean height of the waveform (Tamx, a measure of renal blood flow) occurred in the control subjects while they were breathing air or oxygen. The pulsatility index of the patients with chronic obstructive airways disease was significantly greater than that in the control subjects breathing air (1.44 (SD 0.28) v 1.03 (0.14). Breathing oxygen was associated with an increase in TcPO2 in the patients (from 6.9 (1.9) to 11.5 (0.7) kPa), a fall in pulsatility index (from 1.44 (0.28) to 1.26 (0.14) and an increase in Tamx (from 0.187 (0.055) to 0.234 (0.087) m/s). CONCLUSIONS: The results suggest that renal vascular resistance is increased in patients with chronic obstructive airways disease and hypoxaemia and that short term oxygen therapy reduces renal vascular resistance and increases blood flow. Some of the benefits of oxygen therapy in cor pulmonale may be due to improvements in renal haemodynamics.
Use of Plasma Biomarkers at Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: John R. Hurst, Gavin C. Donaldson, Wayomi R. Perera, Tom M. A. Wilkinson, John A. Bilello, Gerry W. Hagan, Rupert S. Vessey, Jadwiga A. Wedzicha
Journal: American Journal of Respiratory and Critical Care Medicine (2006)

This study explores the use of measuring plasma biomarkers at exacerbation of chronic obstructive pulmonary disease (COPD), providing insight into the underlying pathogenesis of these important events.The use of measuring C-reactive protein (CRP) to confirm exacerbation, or to assess exacerbation severity, in COPD is unclear. Furthermore, it is not known whether there may be more useful systemic biomarkers.To assess the use of plasma biomarkers in confirming exacerbation and predicting exacerbation severity.We assessed 36 biomarkers in 90 paired baseline and exacerbation plasma samples from 90 patients with COPD. The diagnosis of exacerbation fulfilled both health care use and symptom-based criteria. Biomarker concentrations were related to clinical indices of exacerbation severity. Interrelationships between biomarkers were examined to gain information on mechanisms of systemic inflammation at exacerbation of COPD.To confirm the diagnosis of exacerbation, the most selective biomarker was CRP. However, this was neither sufficiently sensitive nor specific alone (area under the receiver operating characteristic curve [AUC], 0.73; 95% confidence interval, 0.66-0.80). The combination of CRP with any one increased major exacerbation symptom recorded by the patient on that day (dyspnea, sputum volume, or sputum purulence) significantly increased the AUC to 0.88 (95% confidence interval, 0.82-0.93; p<0.0001). There were no significant relationships between biomarker concentrations and clinical indices of exacerbation severity. Interrelationships between biomarkers suggest that the acute-phase response is related, separately, to monocytic and lymphocytic-neutrophilic pathways.Plasma CRP concentration, in the presence of a major exacerbation symptom, is useful in the confirmation of COPD exacerbation. Systemic biomarkers were not helpful in predicting exacerbation severity. The acute-phase response at exacerbation was most strongly related to indices of monocyte function.
Reactive Nitrogen Species Induced by Hyperglycemia Suppresses Akt Signaling and Triggers Apoptosis by Upregulating Phosphatase PTEN (Phosphatase and Tensin Homologue Deleted on Chromosome 10) in an LKB1-Dependent Manner
Authors: Ping Song, Yong Wu, Jian Xu, Zhonglin Xie, Yunzhou Dong, Miao Zhang, Ming-Hui Zou
Journal: Circulation (2007)

Background— Oxidative stress plays a causal role in vascular injury in diabetes mellitus, but the mechanisms and targets remain poorly understood. Methods and Results— Exposure of cultured human umbilical vein endothelial cells to either peroxynitrite (ONOO − ) or high glucose significantly inhibited both basal and insulin-stimulated Akt phosphorylation at Ser473 and Akt activity in parallel with increased apoptosis, phosphorylation, and activity of phosphatase and tensin homologue deleted on chromosome 10 (PTEN). Furthermore, protein kinase B/Akt inhibition induced by ONOO − or high glucose and apoptosis triggered by high glucose could be abolished by transfection of PTEN-specific small interfering RNA, suggesting that PTEN mediated the Akt inhibition by ONOO − . In addition, exposure of human umbilical vein endothelial cells to ONOO − or high glucose remarkably increased Ser428 phosphorylation of LKB1, a tumor suppressor. Interestingly, the ONOO − -enhanced PTEN phosphorylation and Akt inhibition can be blocked by LKB1-specific small interfering RNA. Consistently, LKB1 phosphorylated PTEN at Ser380/Thr382/383 in vitro, suggesting that LKB1 might act as an upstream kinase for PTEN. Compared with nondiabetic mice, the levels of PTEN, LKB1-Ser428 phosphorylation, and 3-nitrotyrosine (a biomarker of ONOO − ) were significantly increased in the aortas of streptozotocin-induced diabetic mice, which was in parallel with a reduction in Akt-Ser473 phosphorylation and an increase in apoptosis. Furthermore, administration of PTEN-specific small interfering RNA suppressed diabetes-enhanced apoptosis and Akt inhibition. Finally, treatment with Tempol, a superoxide dismutase mimetic, and insulin, both of which reduced the ONOO − formation, markedly reduced diabetes-enhanced LKB1-Ser428 phosphorylation, PTEN, and apoptosis in the endothelium of mouse aortas. Conclusion— We conclude that hyperglycemia triggers apoptosis by inhibiting Akt signaling via ONOO − -mediated LKB1-dependent PTEN activation.
Tumor-Specific Cytotoxic T Cells Are Crucial for Efficacy of Immunomodulatory Antibodies in Patients with Lung Cancer
Authors: Joachim G. Aerts, Joost P. Hegmans
Journal: Cancer Research (2013)

There is growing evidence that activation of the immune system may be an effective treatment for patients with either small cell lung cancer or non-small cell lung cancer (NSCLC). Immunomodulatory antibodies directed against cytotoxic T cell-associated antigen 4 (CTLA-4/CD152) and programmed cell death ligand 1 (PDL1/CD274) showed clinical efficacy in patients with lung cancer. The key immune cells responsible for antitumor activity are the CTLs. The presence of these tumor-directed CTLs, both in number and functionality, is a prerequisite for the immune system to attack cancer cells. Immunomodulatory agents attempt to increase the efficacy of CTL activity. Thus, the limited number of patients who benefit from immunomodulatory antibodies may be caused by either an inadequate number or the impairment of CTL activity by the hostile environment created by the tumor. In this review, we discuss tumor-induced impairment of CTLs and experimental treatments that can stimulate T-cell responses and optimize specific CTL function. We discuss 2 types of immune cells with known suppressive capacity on CTLs that are of pivotal importance in patients with lung cancer: regulatory T cells and myeloid-derived suppressor cells.
Diverse Patterns of T-Cell Response against Multiple Newly Identified Human Y Chromosome–Encoded Minor Histocompatibility Epitopes
Authors: Yishai Ofran, Haesook T. Kim, Vladimir Brusic, Loren Blake, Michael Mandrell, Catherine J. Wu, Stefanie Sarantopoulos, Roberto Bellucci, Derin B. Keskin, Robert J. Soiffer, Joseph H. Antin, Jerome Ritz
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Donor T cells respond to minor histocompatibility antigens (mHA), resulting in both graft-versus-host disease and graft versus leukemia after allogeneic hematopoietic stem cell transplantation. Because relatively few mHAs are known, we developed a new approach to predict and subsequently validate candidate mHA. Experimental Design: We developed an algorithm based on genetic disparities between Y chromosome–encoded and X chromosome–encoded proteins and known requirements for binding to HLA class I molecules to predict Y chromosome–derived, HLA A*0201–restricted peptides (HY) and ranked peptides based on potential immunogenicity. We evaluated T-cell responses to 41 candidate peptides in 28 male recipients with female donors (FM), 22 male recipients with male donors (MM), and 26 normal individuals. All patients and donors were HLA A*0201 positive. Results: Thirteen peptides derived from five proteins elicited significantly greater T-cell responses in FM patients compared with MM patients and in normal females compared with normal males. Six peptides were more immunogenic than the only previously known HLA A*0201–restricted Y-encoded mHA. Twenty-seven of 28 FM patients responded to at least one HY peptide, but despite a common Y chromosome mismatch and expression of HLA A*0201, each patient responded to a unique set of peptides. Conclusions: Novel HLA A*0201–restricted HY epitopes can be predicted and validated in patients after allogeneic hematopoietic stem cell transplantation. Highly diverse patterns of T-cell response against these epitopes have been identified. Prospective monitoring of responses to large panels of immunogenic peptides can facilitate the identification of clinically relevant targets of graft-versus-host disease and graft versus leukemia. Clin Cancer Res; 16(5); 1642–51
Detection of leukotriene B4 in cardiac tissue and its role in infarct extension through leucocyte migration
Authors: K. SASAKI, A. UENO, M. KATORI, R. KIKAWADA
Journal: Cardiovascular Research (1988)

Journal Article Detection of leukotriene B4 in cardiac tissue and its role in infarct extension through leucocyte migration Get access KOUJI SASAKI, KOUJI SASAKI From the Department of Pharmacology and Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar AKINORI UENO, AKINORI UENO From the Department of Pharmacology and Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar MAKOTO KATORI, MAKOTO KATORI From the Department of Pharmacology and Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar RYUICHI KIKAWADA RYUICHI KIKAWADA From the Department of Pharmacology and Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, Japan Search for other works by this author on: Oxford Academic PubMed Google Scholar Cardiovascular Research, Volume 22, Issue 2, February 1988, Pages 142–148, https://doi.org/10.1093/cvr/22.2.142 Published: 01 February 1988 Article history Received: 18 February 1987 Accepted: 20 August 1987 Published: 01 February 1988
Behavioral Counseling to Promote Physical Activity and a Healthful Diet to Prevent Cardiovascular Disease in Adults: A Systematic Review for the U.S. Preventive Services Task Force
Authors: Jennifer S. Lin, Elizabeth O'Connor, Evelyn P. Whitlock, Tracy L. Beil
Journal: Annals of Internal Medicine (2010)

Background: Poor diet and lack of physical activity can worsen cardiovascular health, yet most Americans do not meet diet and physical activity recommendations. Purpose: To assist the U.S. Preventive Services Task Force in updating its previous recommendations by systematically reviewing trials of physical activity or dietary counseling to prevent cardiovascular disease. Data Sources: MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials (2001 to January 2010), experts, and existing systematic reviews. Study Selection: Two investigators independently reviewed 13 562 abstracts and 481 articles against a set of a priori inclusion criteria and critically appraised each study by using design-specific quality criteria. Data Extraction and Analysis: Data from 73 studies (109 articles) were abstracted by one reviewer and checked by a second reviewer. Random-effects meta-analyses were conducted for multiple intermediate health and behavioral outcomes. Data Synthesis: Long-term observational follow-up of intensive sodium reduction counseling showed a decrease in the incidence of cardiovascular disease; however, other direct evidence for reduction in disease morbidity is lacking. High-intensity dietary counseling, with or without physical activity counseling, resulted in changes of −0.3 to −0.7 kg/m2 in body mass index (adiposity), −1.5 mm Hg (95% CI, −0.9 to −2.1 mm Hg) in systolic blood pressure, −0.7 mm Hg (CI, −0.6 to −0.9 mm Hg) in diastolic pressure, −0.17 mmol/L (CI, −0.09 to −0.25 mmol/L) (−6.56 mg/dL [CI, −3.47 to −9.65 mg/dL]) in total cholesterol level, and −0.13 mmol/L (CI, −0.06 to −0.21 mmol/L) (−5.02 mg/dL [CI, −2.32 to −8.11 mg/dL]) in low-density lipoprotein cholesterol level. Medium- and high-intensity counseling resulted in moderate to large changes in self-reported dietary and physical activity behaviors. Limitations: Meta-analyses for some outcomes had large statistical heterogeneity or evidence for publication bias. Only 11 trials followed outcomes beyond 12 months. Conclusion: Counseling to improve diet or increase physical activity changed health behaviors and was associated with small improvements in adiposity, blood pressure, and lipid levels. Primary Funding Source: Agency for Healthcare Research and Quality.
Eosinophil chemotactic activity in bronchoalveolar lavage from idiopathic pulmonary fibrosis is dependent on cytokine priming of eosinophils
Authors: KA Boomars, RC Schweizer, P Zanen, JM van den Bosch, JW Lammers, L Koenderman
Journal: European Respiratory Journal (1998)

Increased numbers of eosinophils have been found in bronchoalveolar lavage (BAL) fluid obtained from patients with idiopathic pulmonary fibrosis (IPF). This suggests the presence of one or more cytokines in the lung tissue of patients with IPF, which are involved in the induction of migration of eosinophils towards the pulmonary compartment. To evaluate this hypothesis, we studied migratory responses of blood eosinophils towards BAL fluid. Migratory responses were tested by means of a modified Boyden chamber assay in 21 patients with IPF and 14 healthy controls. Experiments were performed with unprimed eosinophils and in vitro primed eosinophils (preincubated with 10(-11) M granulocyte macrophage-colony-stimulating factor). Changes in intracellular free Ca2+ ([Ca2+]i) in eosinophils in response to BAL fluid were also investigated, to characterize putative chemotaxins further. Chemotactic responses of eosinophils were observed towards BAL fluid from both patients with IPF and controls, provided that the eosinophils were primed. No changes in [Ca2+]i in eosinophils were detected in response to BAL fluid. Furthermore, neither a blocking antibody against interleukin-8 nor one against regulated on activation, normal T-cell, expressed and secreted (RANTES) influenced the response. Since a chemotactic response of in vitro primed eosinophils was also observed towards bronchoalveolar lavage fluid from normals, it was concluded, that in idiopathic pulmonary fibrosis, apart from the presence of a chemotactic factor in the lung tissue, other mechanisms such as priming of eosinophils in the peripheral blood are responsible for the extravasation of eosinophils into the pulmonary compartment. As no changes in [Ca2+]i were observed in the eosinophils after incubation with bronchoalveolar lavage fluid, the chemotaxin responsible for the migratory responses is probably not one of the known eosinophil-activating chemokines.
Deleterious effects of calcium channel blockade on pressure transmission and glomerular injury in rat remnant kidneys.
Authors: K A Griffin, M M Picken, A K Bidani
Journal: Journal of Clinical Investigation (1995)

Hypertensive mechanisms are postulated to play a major role in the progressive glomerulosclerosis (GS) after renal mass reduction. But, in contrast to converting enzyme inhibitors, BP reduction by calcium channel blockers, has not provided consistent protection. Radiotelemetric BP monitoring for 7 wk was used to compare nifedipine (N) and enalapril (E) in the rat approximately 5/6 renal ablation model. After the first week, rats received N, E, or no treatment (C). The overall averaged systolic BP in C (173 +/- 7 mmHg) was reduced by both E and N (P < 0.001), but E was more effective (113 +/- 2 vs. 134 +/- 3 mmHg, P < 0.01). GS was prevented by E (2 +/- 1 vs. 26 +/- 5% in C) but not by N (25 +/- 6%). GS correlated well with the overall averaged BP in individual animals of all groups, but the slope of the relationship was significantly steeper in N compared with C+E rats (P < 0.02), suggesting greater pressure transmission to the glomeruli and GS for any given BP. Since autoregulatory mechanisms provide the primary protection against pressure transmission, renal autoregulation was examined at 3 wk in additional rats. Autoregulation was impaired in C rats, was not additionally altered by E, but was completely abolished by N. These data demonstrate the importance of autoregulatory mechanisms in the pathogenesis of hypertensive injury and suggest that calcium channel blockers which adversely affect pressure transmission may not provide protection despite significant BP reduction.
Mechanism of Cell Cycle Regulation by FIP200 in Human Breast Cancer Cells
Authors: Zara K. Melkoumian, Xu Peng, Boyi Gan, Xiaoyang Wu, Jun-Lin Guan
Journal: Cancer Research (2005)

Abstract FIP200 is a novel protein inhibitor for focal adhesion kinase (FAK), which binds to FAK directly and inhibits its kinase activity and associated cellular functions, such as cell adhesion, spreading, and motility in fibroblasts. Here we show that FIP200 inhibits G1-S phase progression, proliferation, and clonogenic survival in human breast cancer cells. Consistent with the G1 arrest induced by FIP200, we found that FIP200 increased p21 and decreased cyclin D1 protein levels in breast cancer cells. In addition, FIP200 significantly induced p21 promoter activity in MCF-7 cells and this response was abolished upon deletion of p53 binding sites within p21 promoter. Furthermore, we found that FIP200 could interact with exogenous and endogenous p53 protein and significantly increase its half-life compared with the control cells. We also found that the NH2-terminal 154 residues of FIP200 were sufficient to mediate p53 interaction and G1 arrest in cells. The increase in p53 half-life correlated with the increased phosphorylation at Ser15 and decreased proteasomal degradation via ubiquitin and Hdm2-independent mechanism. Stabilization of p53 by FIP200 could be partially reversed by NQO1 inhibitor, dicoumarol. In contrast to p53, FIP200 decreased cyclin D1 protein half-life by promoting proteasome-dependent degradation of cyclin D1. In summary, our results suggest that FIP200 increases p21 protein levels via stabilization of its upstream regulator p53 and decreases cyclin D1 protein by promoting its degradation. Both effects are critical for FIP200-induced G1 arrest and may contribute to the putative antitumor activities of FIP200 in breast cancer.
Photodynamic Therapy for Malignant Pleural Mesothelioma
Authors: Joseph S. Friedberg
Journal: Journal of the National Comprehensive Cancer Network (2012)

Surgery is the treatment option most likely to be associated with prolonged remission in patients with malignant pleural mesothelioma. However, it remains investigational and must always be combined with other modalities to treat the microscopic disease that remains after the most aggressive operations. Improvements in quality of life for appropriate patients with this rare yet incurable cancer may be obtained with less drastic lung-sparing surgical procedures along with intraoperative use of photodynamic therapy (PDT). Very encouraging survival results have been obtained with the combination of surgery and PDT, which requires the well-orchestrated collaborative effort of an extensive team of professionals, from thoracic surgeons and radiation oncologists to basic science researchers. Multi-institutional trials are necessary to duplicate these early findings and shed more light on the tumor-directed immune response of this surgically based multimodal treatment.
Long-Term Efficacy of Sigmoidoscopy in the Reduction of Colorectal Cancer Incidence
Authors: P. A. Newcomb, B. E. Storer, L. M. Morimoto, A. Templeton, J. D. Potter
Journal: JNCI Journal of the National Cancer Institute (2003)

Screening sigmoidoscopy is associated with a reduction in both the incidence and mortality of colorectal cancer. Although current guidelines recommend sigmoidoscopy screening every 5 years, the duration of risk reduction is not known. We conducted a population-based case-control study to examine the association between sigmoidoscopy screening and colorectal cancer incidence. We collected information on screening history and risk factors from case patients with distal (n = 1026) and proximal (n = 642) colorectal cancer and from 1294 control subjects from October 1998 through February 2002. Screening sigmoidoscopy was associated with a statistically significant reduction in the incidence of distal colorectal cancer (odds ratio [OR] = 0.24, 95% confidence interval [CI] = 0.17 to 0.33). These reductions were sustained for up to 16 years with little attenuation. We also observed strong inverse associations between cancer incidence and sigmoidoscopy in analyses that included subjects with symptom-related tests. Current recommendations regarding the frequency of sigmoidoscopy screening may be unnecessarily aggressive.