tbuckley/cabot-search huggingface dataset:
Biological markers of cardiac damage are not related to measures of cardiac systolic and diastolic function using cardiovascular magnetic resonance and echocardiography after an acute bout of prolonged endurance exercise
Authors: M Wilson, R O'Hanlon, S Prasad, D Oxborough, R Godfrey, F Alpendurada, G Smith, J Wong, S Basavarajaiah, S Sharma, A Nevill, David Gaze, K George, G Whyte
Journal: British Journal of Sports Medicine (2009)

Seventeen male participants (mean (SD) (range): age 33.5 (6.5) years (46-26 years), body mass 80 (9.2) kg (100-63 kg), height 1.81 (0.06) m (1.93- 1.70 m)) ran a marathon to investigate the relationship between systolic function (using cardiac magnetic resonance (CMR)) and diastolic function (using echocardiography) against biomarkers of cardiac damage.Echocardiographic and cardiac troponin I (cTnI)/N-terminal pro-B-type natriuretic peptide (NTproBNP) data were collected 24 h premarathon, immediately postmarathon and 6 h postmarathon. CMR data were collected 24 h premarathon and at 6 h postmarathon.Body mass was significantly reduced postmarathon (80 (9.2) vs 78.8 (8.6) kg; p<0.001). There was a significant E/A reduction postmarathon (1.11 (0.34) vs 1.72 (0.44); p<0.05) that remained depressed 6 h postmarathon (1.49 (0.43); p<0.05). CMR demonstrated left ventricular end-diastolic and end-systolic volumes were reduced postmarathon, with a preserved stroke volume. Left ventricular ejection fraction 6 h postmarathon significantly increased (64.4% (4.2%) vs 67.4% (5%); p<0.05). There were significant elevations in cTnI (0.00 vs 0.04 (0.03) μg/l; p<0.05) and NTproBNP (37.4 (24.15) ng/l vs 59.34 (43.3) ng/l; p<0.05) immediately postmarathon. Eight runners had cTnI elevations immediately postmarathon above acute myocardial infarction cutoff levels (≥0.03 μg/l). No correlations between cTnI/NTproBNP and measures of diastolic function (E, A, E/A, isovolumic relaxation time, E deceleration time and E/E') or measures of systolic function (stroke volume or ejection fraction) were observed immediately postmarathon or 6 h postmarathon.Biomarkers of cardiac damage after prolonged exercise are not associated with either systolic or diastolic functional measures.
The C-terminal region of Bfl-1 sensitizes non-small cell lung cancer to gemcitabine-induced apoptosis by suppressing NF-κB activity and down-regulating Bfl-1
Authors: Min-Kyoung Kim, Yoon-Kyung Jeon, Jong-Kyu Woo, Yun Choi, Dae-Han Choi, Yeul-Hong Kim, Chul-Woo Kim
Journal: Molecular Cancer (2011)

Gemcitabine is used to treat several cancers including lung cancer. However, tumor cells often escape gemcitabine-induced cell death via various mechanisms, which include modulating bcl-2 family members and NF-κB activation. We previously reported that the C-terminal region of Bfl-1 fused with GFP (BC) is sufficient to induce apoptosis in 293T cells. In the present study, we investigated the anti-tumor effect of combined BC gene therapy and gemcitabine chemotherapy in vitro and in vivo using non-small cell lung cancer cell lines and a xenograft model. Cell lines were resistant to low dose gemcitabine (4-40 ng/ml), which induced NF-κB activation and concomitant up-regulation of Bfl-1 (an NF-κB-regulated anti-apoptotic protein). BC induced the apoptosis of A549 and H157 cells with caspase-3 activation. Furthermore, co-treatment with BC and low dose gemcitabine synergistically and efficiently induced mitochondria-mediated apoptosis in these cells. When administered alone or with low dose gemcitabine, BC suppressed NF-κB activity, inhibited the nuclear translocation of p65/relA, and down-regulated Bfl-1 expression. Furthermore, direct suppression of Bfl-1 by RNA interference sensitized cells to gemcitabine-induced cell death, suggesting that Bfl-1 importantly regulates lung cancer cell sensitivity to gemcitabine. BC and gemcitabine co-treatment also showed a strong anti-tumor effect in a nude mouse/A549 xenograft model. These results suggest that lung cancer cells become resistant to gemcitabine via NF-κB activation and the subsequent overexpression of Bfl-1, and that BC, which has both pro-apoptotic and NF-κB inhibitory effects, could be harnessed as a gene therapy to complement gemcitabine chemotherapy in non-small cell lung cancer.
Recombinant human activated protein C (rhAPC; drotrecogin alfa [activated]) has minimal effect on markers of coagulation, fibrinolysis, and inflammation in acute human endotoxemia
Authors: Ulla Derhaschnig, Rosemarie Reiter, Paul Knöbl, Magdalena Baumgartner, Priska Keen, Bernd Jilma
Journal: Blood (2003)
Integrin-dependence of Lymphocyte Entry into the Splenic White Pulp
Authors: Charles G. Lo, Theresa T. Lu, Jason G. Cyster
Journal: The Journal of Experimental Medicine (2003)

The steps involved in lymphocyte homing to the white pulp cords of the spleen are poorly understood. We demonstrate here that the integrins lymphocyte function associated (LFA)-1 and α4β1 make essential and mostly overlapping contributions necessary for B cell migration into white pulp cords. T cell entry to the white pulp is also reduced by blockade of LFA-1 and α4β1. The LFA-1 ligand, intercellular adhesion molecule 1 is critical for lymphocyte entry and both hematopoietic cells and radiation-resistant cells contribute to this requirement. Vascular cell adhesion molecule 1 contributes to the α4β1 ligand requirement and a second ligand, possibly fibronectin, also plays a role. By contrast with the entry requirements, antigen-induced movement of B cells from follicles to the outer T zone is not prevented by integrin blocking antibodies. Comparison of the distribution of integrin-blocked B cells and B cells treated with the Gαi inhibitor, pertussis toxin, early after transfer reveals in both cases reduced accumulation in the inner marginal zone. These observations suggest that chemokine receptor signaling and the integrins LFA-1 and α4β1 function together to promote lymphocyte transit from the marginal zone into white pulp cords.
Book of the month: Cicely Saunders–Founder of the Hospice Movement: Selected Letters 1959-1999
Authors: Richard Carter
Journal: Journal of the Royal Society of Medicine (2003)

‘The main duty of one who edits another's letters,’ writes Professor David Clark, ‘is to intrude as little as possible upon what they have to tell us.’ In editing the letters of Dame Cicely Saunders he sets out his conditions of working with such clarity that it is appropriate to begin a review by considering his own contribution.
Towards the uniform distribution of null P values on Affymetrix microarrays
Authors: Anthony A Fodor, Timothy L Tickle, Christine Richardson
Journal: Genome biology (2007)

Methods to control false-positive rates require that P values of genes that are not differentially expressed follow a uniform distribution. Commonly used microarray statistics can generate P values that do not meet this assumption. We show that poorly characterized variance, imperfect normalization, and cross-hybridization are among the many causes of this non-uniform distribution. We demonstrate a simple technique that produces P values that are close to uniform for nondifferentially expressed genes in control datasets.
Role of the endothelin axis in astrocyte- and endothelial cell-mediated chemoprotection of cancer cells
Authors: Seung Wook Kim, Hyun Jin Choi, Ho-Jeong Lee, Junqin He, Qiuyu Wu, Robert R. Langley, Isaiah J. Fidler, Sun-Jin Kim
Journal: Neuro-Oncology (2014)

Recent evidence suggests that astrocytes protect cancer cells from chemotherapy by stimulating upregulation of anti-apoptotic genes in those cells. We investigated the possibility that activation of the endothelin axis orchestrates survival gene expression and chemoprotection in MDA-MB-231 breast cancer cells and H226 lung cancer cells.Cancer cells, murine astrocytes, and murine fibroblasts were grown in isolation, and expression of endothelin (ET) peptides and ET receptors (ETAR and ETBR) compared with expression on cancer cells and astrocytes (or cancer cells and fibroblasts) that were co-incubated for 48 hours. Type-specific endothelin receptor antagonists were used to evaluate the contribution of ETAR and ETBR to astrocyte-induced activation of the protein kinase B (AKT)/mitogen-activated protein kinase (MAPK) signal transduction pathways, anti-apoptotic gene expression, and chemoprotection of cancer cells. We also investigated the chemoprotective potential of brain endothelial cells and microglial cells.Gap junction signaling between MDA-MB-231 cancer cells and astrocytes stimulates upregulation of interleukin 6 (IL-6) and IL-8 expression in cancer cells, which increases ET-1 production from astrocytes and ET receptor expression on cancer cells. ET-1 signals for activation of AKT/MAPK and upregulation of survival proteins that protect cancer cells from taxol. Brain endothelial cell-mediated chemoprotection of cancer cells also involves endothelin signaling. Dual antagonism of ETAR and ETBR is required to abolish astrocyte- and endothelial cell-mediated chemoprotection.Bidirectional signaling between astrocytes and cancer cells involves upregulation and activation of the endothelin axis, which protects cancer cells from cytotoxicity induced by chemotherapeutic drugs.
The global burden of low back pain: estimates from the Global Burden of Disease 2010 study
Authors: Damian Hoy, Lyn March, Peter Brooks, Fiona Blyth, Anthony Woolf, Christopher Bain, Gail Williams, Emma Smith, Theo Vos, Jan Barendregt, Chris Murray, Roy Burstein, Rachelle Buchbinder
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Objective</h3> To estimate the global burden of low back pain (LBP). <h3>Methods</h3> LBP was defined as pain in the area on the posterior aspect of the body from the lower margin of the twelfth ribs to the lower glutaeal folds with or without pain referred into one or both lower limbs that lasts for at least one day. Systematic reviews were performed of the prevalence, incidence, remission, duration, and mortality risk of LBP. Four levels of severity were identified for LBP with and without leg pain, each with their own disability weights. The disability weights were applied to prevalence values to derive the overall disability of LBP expressed as years lived with disability (YLDs). As there is no mortality from LBP, YLDs are the same as disability-adjusted life years (DALYs). <h3>Results</h3> Out of all 291 conditions studied in the Global Burden of Disease 2010 Study, LBP ranked highest in terms of disability (YLDs), and sixth in terms of overall burden (DALYs). The global point prevalence of LBP was 9.4% (95% CI 9.0 to 9.8). DALYs increased from 58.2 million (M) (95% CI 39.9M to 78.1M) in 1990 to 83.0M (95% CI 56.6M to 111.9M) in 2010. Prevalence and burden increased with age. <h3>Conclusions</h3> LBP causes more global disability than any other condition. With the ageing population, there is an urgent need for further research to better understand LBP across different settings.
N-α-Acetyltransferase 10 Protein Suppresses Cancer Cell Metastasis by Binding PIX Proteins and Inhibiting Cdc42/Rac1 Activity
Authors: Kuo-Tai Hua, Ching-Ting Tan, Gunnar Johansson, Jang-Ming Lee, Pei-Wen Yang, Hsin-Yi Lu, Chi-Kuan Chen, Jen-Liang Su, PoShen B. Chen, Yu-Ling Wu, Chia-Chun Chi, Hsin-Jung Kao, Hou-Jung Shih, Min-Wei Chen, Ming-Hsien Chien, Pai-Sheng Chen, Wei-Jiunn Lee, Tsu-Yao Cheng, George Rosenberger, Chee-Yin Chai, Chih-Jen Yang, Ming-Shyan Huang, Tsung-Ching Lai, Teh-Ying Chou, Michael Hsiao, Min-Liang Kuo
Journal: Cancer Cell (2011)
ACE inhibitors and anaphylactoid reactions to high-flux membrane dialysis
Authors: CharlesA. Dinarello, M.A. Alvarez-Lara, A. Martin-Malo, M. Espinosa, D. Castillo, P. Aljama, C. Tielemans, J.L. Vanherweghem, A. Blumberg, R. Cuvelier, J.F. De Fremont, F. Dehout, P. Dupont, C. Richard, J.C. Stolear, R. Wens
Journal: The Lancet (1991)
B. Lowell Langille (1947–2008)
Authors: Michelle Bendeck, Avrum Gotlieb
Journal: Circulation Research (2009)

Princess Margaret Hospital in Toronto.We will miss Lowell's leadership in our department and in the world of vascular biology and atherosclerosis.Lowell was held in very high regard by all of us, and not the least by his many trainees.We appreciated his enthusiasm for science, his persistence in asking and answering relevant questions, and, in particular, his patience.He would often stop someone as he or she passed the open door of his office to show an exciting live image clip of a particular protein function that he was studying in an endothelial or smooth muscle cell.We often felt that we had trouble "keeping up," but he was always willing to stop and explain the physics of vascular biology.His honesty and integrity will serve as an example to guide us in science and in life.
Evidence of a Relationship Between Infant Birth Weight and Later Diabetes and Impaired Glucose Regulation in a Chinese Population
Authors: Xinhua Xiao, Zhen-Xin Zhang, Harvey Jay Cohen, Heng Wang, Wenhui Li, Tong Wang, Tao Xu, Aimin Liu, Ming-Ying Gai, Shen Ying, Ole Schmitz, Zeng Yi
Journal: Diabetes Care (2008)

The aim of this study was to determine the influence of birth weight, a marker of fetal growth, on the development of later impaired glucose metabolism throughout the life span of people living in China.We recorded detailed anthropometric data including height, weight, and health status and measured blood glucose levels and insulin concentrations after fasting and at 120 min of a standard oral glucose tolerance test from 2,019 eligible subjects born between 1921 and 1954 to investigate the risk of developing type 2 diabetes and impaired glucose regulation (IGR).The diabetes and IGR groups were characterized by significantly lower birth weight (P < 0.001), smaller head circumference (P < 0.001), smaller ponderal index (P = 0.007), and shorter length (P = 0.004) compared with those in the normal glucose tolerance group. Using multiple logistic regression analysis, we observed that birth weight remained significantly associated with diabetes and IGR after adjustments for possible confounding variables at birth and in adult life such as sex, age, central obesity, smoking status, alcohol consumption, dyslipidemia, family history of diabetes, and occupational status (P = 0.027). There was a significantly increased risk of getting diabetes and IGR for those with low birth weight (odds ratio 1.748 [95% CI 1.018-3.001], P = 0.043).The results confirm that lower birth weight is an independent risk factor for later diabetes or IGR and show for the first time that this risk factor also applies for a Chinese population.
Bone Sialoprotein Mediates Human Endothelial Cell Attachment and Migration and Promotes Angiogenesis
Authors: Akeila Bellahcène, Karine Bonjean, Berthold Fohr, Neal S. Fedarko, Frank A. Robey, Marian F. Young, Larry W. Fisher, Vincent Castronovo
Journal: Circulation Research (2000)

Abstract —Bone sialoprotein (BSP) is a secreted glycoprotein primarily found in sites of biomineralization. Recently, we demonstrated that BSP is strongly upregulated in osteotropic cancers and particularly those that exhibit microcalcifications. BSP contains an Arg-Gly-Asp (RGD) motif found in other adhesive molecules that interact with cellular integrins. In bone, BSP has been shown to mediate the attachment of osteoblasts and osteoclasts via α v β 3 integrin receptors. Ligands for α v β 3 integrin are considered to play a central role during angiogenesis. Therefore, we used human umbilical vein endothelial cells (HUVECs) to study the potential role of BSP in angiogenesis. We found that purified eukaryotic recombinant human BSP (rhBSP) is able to promote both adhesion and chemotactic migration of HUVECs in a dose-dependent manner. These interactions involve HUVEC α v β 3 integrin receptors and the RGD domain of BSP. Indeed, HUVECs attach to a recombinant BSP fragment containing the RGD domain, whereas this response is not observed with the same fragment in which RGD has been mutated to Lys-Ala-Glu (KAE). A cyclic RGD BSP peptide inhibits both adhesion and migration of HUVECs to rhBSP. Moreover, anti-α v β 3 but not anti-α v β 5 monoclonal antibodies also prevent BSP-mediated adhesion and migration of HUVECs. We observed that both rhBSP and the RGD BSP recombinant fragment stimulated ongoing angiogenesis on the chorioallantoic chick membrane assay. BSP angiogenic activity was inhibited by anti-α v β 3 antibody, and the KAE BSP fragment was inactive. Our findings represent the first report implicating BSP in angiogenesis. BSP could play a critical role in angiogenesis associated with bone formation and with tumor growth and metastatic dissemination.
Development of a risk score for atrial fibrillation (Framingham Heart Study): a community-based cohort study
Authors: Renate B Schnabel, Lisa M Sullivan, Daniel Levy, Michael J Pencina, Joseph M Massaro, Ralph B D'Agostino, Christopher Newton-Cheh, Jennifer F Yamamoto, Jared W Magnani, Thomas M Tadros, William B Kannel, Thomas J Wang, Patrick T Ellinor, Philip A Wolf, Ramachandran S Vasan, Emelia J Benjamin
Journal: The Lancet (2009)
Cavitary lung masses in SLE patients: an unusual manifestation of CMV infection
Authors: M. Najjar, A.K. Siddiqui, L. Rossoff, R.I. Cohen
Journal: European Respiratory Journal (2004)

The typical radiographical findings of cytomegalovirus pneumonitis are bilateral interstitial infiltrates. In this study, the current authors describe two patients on corticosteroid treatment for systemic lupus erythematosus, complicated by histologically confirmed cytomegalovirus pneumonitis, presenting as cavitary masses. This rare presentation of cytomegalovirus pneumonitis broadens the differential diagnosis of cavitary lesions to include cytomegalovirus infection in immunocompromised individuals.
A small outbreak of Legionnaires' disease in a cargo ship under repair
Authors: J.A. Caylà, R. Maldonado, J. González, T. Pellicer, D. Ferrer, C. Pelaz, J. Gracia, B. Baladrón, A. Plaséncia
Journal: European Respiratory Journal (2001)

It was reported that two mechanics working on a cargo ship under repair in the port of Barcelona had died after having fever. An investigation was made into the possibility of any additional cases and the presence of Legionella pneumophila in the ship they were repairing and in their hotel. The contaminated water system was treated with sodium hypochlorite. Both patients died after having been repeatedly diagnosed as having influenza. The two cases occurred among those who had been working with the pump of the ship's water system, while no cases were observed among the other workers (p = 0.02). Various serogroups of L. pneumophila were isolated from the ship's water pump and distribution system. However, organism of serogroup 1, subgroup Pontiac (Knoxville) were identified with identical deoxyribonucleic acid (DNA) patterns in the lung tissue of one patient and in the cooling water circuit valve of the ship's water pump. The first postintervention control water samples showed no further growth of legionella, but serogroups 4 and 8 were identified 8 months later. This legionellosis outbreak, although small, was highly lethal, probably due to the high levels of bacteria to which the patients were exposed and also because of the failure of correct diagnosis. International recommendations on prevention and control of legionellosis, which include ships under repair, are required.
In vitro production of anti‐RBC antibodies and cytokines in chronic lymphocytic leukemia
Authors: W. Barcellini, R. Montesano, G. Clerici, A. Zaninoni, F.G. Imperiali, R. Calori, A. Cortelezzi, A. Zanella
Journal: American Journal of Hematology (2002)

B-chronic lymphocytic leukemia (B-CLL) patients have a high prevalence of autoimmune phenomena, mainly autoimmune hemolytic anemia (AIHA). Immunoregulatory cytokines play a role in the regulation of both autoimmunity and leukemic B-cell growth. Mitogen-stimulated direct antiglobulin test (MS-DAT) is a recently described test able to disclose latent anti-RBC autoimmunity in AIHA. We investigated the prevalence of anti-RBC autoimmunity by MS-DAT and the pattern of cytokine production by PHA-stimulated whole blood cultures from 69 B-CLL patients and 53 controls. Results showed that anti-RBC IgG values in unstimulated, PHA-, PMA-, and PWM-stimulated cultures were significantly higher in B-CLL patients compared with controls. In B-CLL, the prevalence of anti-RBC autoimmunity was 28.9% by MS-DAT, compared with 4.3% by the standard DAT. Production of IFN-gamma, IL-2, IL-13, TNF-alpha, sCD23, and sCD30 was significantly increased in all B-CLL patients compared with controls, whereas there was no difference in IL-4, IL-6, IL-10, and TGF-beta production. Multivariate analysis showed that IL-4 was significantly increased in MS-DAT-positive compared with -negative patients. Patients with autoantibody positivity displayed greater IFN-gamma production than negative patients. These data are in line with the hypothesis that autoimmune phenomena in B-CLL are associated with an imbalance towards a Th-2-like profile. The elevated prevalence of anti-RBC autoimmunity found by MS-DAT suggests that an underestimated latent autoimmunity exists in B-CLL.
Smoking and Schizophrenia in Population Cohorts of Swedish Women and Men: A Prospective Co-Relative Control Study
Authors: Kenneth S. Kendler, Sara Larsson Lönn, Jan Sundquist, Kristina Sundquist
Journal: American Journal of Psychiatry (2015)

The purpose of this study was to clarify the causes of the smoking-schizophrenia association.Using Cox proportional hazard and co-relative control models, the authors predicted future risk for a diagnosis of schizophrenia or nonaffective psychosis from the smoking status of 1,413,849 women and 233,879 men from, respectively, the Swedish birth and conscript registries.Smoking was assessed in women at a mean age of 27 and in men at a mean age of 18. The mean age at end of follow-up was 46 for women and 26 for men. Hazard ratios for first-onset schizophrenia were elevated both for light smoking (2.21 [95% CI=1.90-2.56] for women and 2.15 [95% CI=1.25-3.44] for men) and heavy smoking (3.45 [95% CI=2.95-4.03] for women and 3.80 [95% CI=1.19-6.60] for men). These associations did not decline when schizophrenia onsets 3-5 years after smoking assessment were censored. When age, socioeconomic status, and drug abuse were controlled for, hazard ratios declined only modestly in both samples. Women who smoked into late pregnancy had a much higher risk for schizophrenia than those who quit early. Hazard ratios predicting nonaffective psychosis in the general population, in cousins, in half siblings, and in full siblings discordant for heavy smoking were, respectively, 2.67, 2.71, 2.54, and 2.18. A model utilizing all relative pairs predicted a hazard ratio of 1.69 (95% CI=1.17-2.44) for nonaffective psychosis in the heavy-smoking member of discordant monozygotic twin pairs.Smoking prospectively predicts risk for schizophrenia. This association does not arise from smoking onset during a schizophrenic prodrome and demonstrates a clear dose-response relationship. While little of this association is explained by epidemiological confounders, a portion arises from common familial/genetic risk factors. However, in full siblings and especially monozygotic twins discordant for smoking, risk for nonaffective psychosis is appreciably higher in the smoking member. These results can help in evaluating the plausibility of various etiological hypotheses for the smoking-schizophrenia association.
ELAVIL IN THE TREATMENT OF AFFECTIVE DISORDERS (AND COMPARISON WITH TOFRĀNIL)
Authors: JANE E. OLTMAN, SAMUEL FRIEDMAN
Journal: American Journal of Psychiatry (1961)

Elavil is an effective antidepressant agent. Side effects, with the dosage employed, are slight. It appears that efficacious antidepressant drugs will produce successful results in some 70 to 75% of patients with affective disorders as a whole.