tbuckley/cabot-search huggingface dataset:
Effect of long haul travel on maximal sprint performance and diurnal variations in elite skeleton athletes
Authors: Nicola Bullock, David T Martin, Angus Ross, Doug Rosemond, Frank E Marino
Journal: British Journal of Sports Medicine (2007)

To quantify the impact of eastward long haul travel on diurnal variations in cortisol, psychological sensations and daily measurements of physical performance.Five elite Australian skeleton athletes undertook a long haul eastward flight from Australia to Canada (LH(travel)), while seven elite Canadian skeleton athletes did not travel (NO(travel)). Salivary cortisol was measured on awakening, 60 min and 120 min after awakening. Psychological sensations were measured with a questionnaire, and maximal 30 m sprints were performed once a day between 09:30 and 11:00 h local time.Compared with baseline, average (SD) resting salivary cortisol decreased by 67% immediately after long haul travel (23.43 (5.71) nMol/l) (mean+/-90% confidence interval) in the LH(travel) group (p = 0.03), while no changes were found in the NO(travel) group (p = 0.74). There were no significant differences in 30 m sprint time between baseline and post-flight tests in the LH(travel) group (p>0.05). The LH(travel) group perceived themselves as "jet lagged" for up to 2 days after the flight (p = 0.01 for both midday lunch and evening dinner).Despite a distinct phase change in salivary cortisol rhythmicity and the athletes perceiving themselves as "jet lagged", minimal disturbances in "one-off" maximal sprinting ability between 09:30 and 11:00 h local time were seen in a group of elite skeleton athletes after long haul eastward travel from Australia to Canada.
A Self-Quenched Galactosamine-Serum Albumin-RhodamineX Conjugate: A “Smart” Fluorescent Molecular Imaging Probe Synthesized with Clinically Applicable Material for Detecting Peritoneal Ovarian Cancer Metastases
Authors: Yukihiro Hama, Yasuteru Urano, Yoshinori Koyama, Andrew J. Gunn, Peter L. Choyke, Hisataka Kobayashi
Journal: Clinical Cancer Research (2007)

Fluorophore activation after cellular internalization of a targeted fluorescently labeled conjugate is an effective molecular imaging strategy to increase target-to-background ratios. The D-galactose receptor on ovarian cancer cells has been used to target self-quenched avidin-rhodamineX conjugates in which the avidin component binds to D-galactose receptor and the rhodamines are optically activated by dequenching only after cellular internalization. As a nonimmunogenic alternative of avidin, galactosamine-conjugated serum albumin (GmSA) targets the D-galactose receptor with higher binding affinity and has more conjugation sites available for rhodamineX than avidin.GmSA was conjugated with 20 rhodamineX molecules (GmSA-20ROX) to create a self-quenching complex, which was compared with a conjugate consisting of GmSA and a single rhodamineX (GmSA-1ROX) in ex vivo chemical activation characteristics, intracellular activation, and in vivo molecular imaging for detecting peritoneal micrometastases of SHIN3 ovarian cancer.GmSA-20ROX was five times brighter than GmSA-1ROX when incubated with SHIN3 ovarian cancer cells for 3 h. Submillimeter SHIN3 ovarian cancer implants in the peritoneal cavity were clearly visualized in vivo with spectral fluorescence imaging due to the high tumor-to-background ratio. The sensitivity and specificity of GmSA-20ROX for implant detection were determined by colocalization of the rhodamineX emission with red fluorescent protein expressed constitutively in the SHIN3 tumor implants. Among 336 lesions, sensitivity and specificity were 99%/99%, respectively, for GmSA-20ROX, whereas the results for GmSA-1ROX were only 24%/100% (n = 388), respectively, for lesions approximately 0.8 mm or greater in diameter.Self-quenched GmSA-20ROX is more efficient than previous d-galactose-targeted fluorescent conjugates.
Trastuzumab emtansine is active on HER-2 overexpressing NSCLC cell lines and overcomes gefitinib resistance
Authors: Daniele Cretella, Francesca Saccani, Federico Quaini, Caterina Frati, Costanza Lagrasta, Mara Bonelli, Cristina Caffarra, Andrea Cavazzoni, Claudia Fumarola, Maricla Galetti, Silvia La Monica, Luca Ampollini, Marcello Tiseo, Andrea Ardizzoni, Pier Giorgio Petronini, Roberta R Alfieri
Journal: Molecular Cancer (2014)

HER-2 represents a relatively new therapeutic target for non small cell lung cancer (NSCLC) patients. The incidence for reported HER-2 overexpression/amplification/mutations ranges from 2 to 20% in NSCLC. Moreover, HER-2 amplification is a potential mechanism of resistance to tyrosine kinase inhibitors of the epidermal growth factor receptor (EGFR-TKI) (about 10% of cases). T-DM1, trastuzumab emtansine is an antibody-drug conjugate composed by the monoclonal antibody trastuzumab and the microtubule polymerization inhibitor DM1. The activity of T-DM1 has been studied in breast cancer but the role of T-DM1 in lung cancer remains unexplored. Antiproliferative and proapoptotic effects of T-DM1 have been investigated in different NSCLC cell lines by MTT, crystal violet staining, morphological study and Western blotting. HER-2 expression and cell cycle were evaluated by flow cytometry and Western blotting. Antibody dependent cell cytotoxicity (ADCC) was measured with a CytoTox assay. Xenografted mice model has been generated using a NSCLC cell line to evaluate the effect of T-DM1 on tumor growth. Moreover, a morphometric and immunohistochemical analysis of tumor xenografts was conducted. In this study we investigated the effect of T-DM1 in a panel of NSCLC cell lines with different HER-2 expression levels, in H1781 cell line carrying HER-2 mutation and in gefitinib resistant HER-2 overexpressing PC9/HER2cl1 cell clone. T-DM1 efficiently inhibited proliferation with arrest in G2-M phase and induced cell death by apoptosis in cells with a significant level of surface expression of HER-2. Antibody-dependent cytotoxicity assay documented that T-DM1 maintained the same activity of trastuzumab. Our data also suggest that targeting HER-2 with T-DM1 potentially overcomes gefitinib resistance. In addition a correlation between cell density/tumor size with both HER-2 expression and T-DM1 activity was established in vitro and in an in vivo xenograft model. Our results indicate that targeting HER-2 with T-DM1 may offer a new therapeutic approach in HER-2 over-expressing lung cancers including those resistant to EGFR TKIs.
The effect of membrane cholesterol content on ion transport processes in plasma membranes
Authors: E Bastiaanse
Journal: Cardiovascular Research (1997)

Cholesterol is a prominent component of mammalian plasma membranes and is one of the factors that determine membrane function. In this review the effects of cholesterol content on transport processes in biological membranes are summarized. Membrane cholesterol affects a variety of membrane proteins, including ion channels, transporters, and receptors. Present concepts concerning the mechanistic basis of lipid-induced modulation of transport protein function range between two extremes: modulation by bulk properties, or by specific interactions. Interest in bulk properties has been focussed mainly on membrane fluidity. The fluidity of biomembranes is diminished particularly by enrichment with cholesterol. As a change in membrane composition alters the environment in which the proteins are dissolved, any process which depends on membrane protein function may be affected by alterations in membrane composition, such as a change in cholesterol content. This review emphasizes the inhibitory effect of cholesterol enrichment on all membrane ATPases studied, and the stimulating effect of cholesterol enrichment on most other membrane transport proteins. Together with the intriguing feature that the cholesterol content of plasma membranes is considerably higher than that of subcellular membranes, there is ample evidence for a significant role of plasma membrane cholesterol in transmembrane protein function.
Points: McIlroy was here. Or was he?
Authors: V E L. Hart
Journal: BMJ (1979)

A N Bamji (14 April, p 973) with great interest.We were medical students resident in separate Dublin hospitals in 1966.At this time McIlroy appeared at the casualty department of the Royal City of Dublin Hospital complaining of chest pain.One of us (JRN) was connecting him to an ECG machine which required to be earthed.Unfortunately, this was not done and the patient obviously experienced an electric shock.He leapt from the trolley and, putting his finger over his tracheostomy, confirmed in no uncertain terms that this was the case.He took his own discharge.Later that evening this somewhat ruffled student called at the Adelaide Hospital three kilometres or so away.There CED was found to be examining McIlroy, still complain- ing of chest pain but not referring to his recent experience.When he saw JRN he had the grace to look a little embarrassed.The ECG machine in the Adelaide Hospital evidently caused the patient no further upset-and the tracing showed no abnormality.Nevertheless, he spent a comfortable night in hospital and subsequently took his own discharge.There is no doubt in our minds that this man was McIlroy....
Long-term follow-up of HER2-overexpressing stage II or III breast cancer treated by anthracycline-free neoadjuvant chemotherapy
Authors: S. Guiu, M. Liegard, L. Favier, I. van Praagh, R. Largillier, B. Weber, D. Coeffic, L. Moreau, F. Priou, M. Campone, J. Gligorov, L. Vanlemmens, V. Trillet-Lenoir, L. Arnould, B. Coudert
Journal: Annals of Oncology (2010)
Differential changes in titin domain phosphorylation increase myofilament stiffness in failing human hearts
Authors: Sebastian Kötter, Laurence Gout, Marion Von Frieling-Salewsky, Anna Eliane Müller, Stefan Helling, Katrin Marcus, Cristobal Dos Remedios, Wolfgang A. Linke, Martina Krüger
Journal: Cardiovascular Research (2013)

Titin-based myofilament stiffness is defined by the expression levels of the cardiac titin-isoforms, N2B and N2BA, and by phosphorylation of the elastic titin domains N2-B unique sequence (N2-Bus) and PEVK. Phosphorylation of the N2-Bus by cGMP-dependent protein kinase (PKG) or cAMP-dependent protein kinase (PKA) decreases titin stiffness, whereas phosphorylation of the PEVK-domain by PKC increases it. We aimed to identify specific sites within the N2-Bus phosphorylated by PKA and PKG and to determine whether differential changes in titin domain phosphorylation could affect passive stiffness in human failing hearts. Using mass spectrometry, we identified seven partly conserved PKA/PKG-targeted phosphorylation motifs in human and rat N2-Bus. Polyclonal antibodies to pSer4185, pSer4010, and pSer4099 in the N2-Bus, and to pSer11878 in the PEVK-region were used to quantify titin-domain phosphorylation by western blot analyses of a set of human donor and failing hearts with similar titin-isoform composition. Passive tension determined in skinned human myocardial fibre preparations was significantly increased in failing compared with donor hearts, notably at shorter sarcomere lengths where titin contributes most to total passive tension. Phosphorylation of Ser4185, Ser4010, and Ser4099 in the N2-Bus was significantly reduced in failing hearts, whereas phosphorylation of Ser11878 in the PEVK-region was increased compared with donor hearts. We conclude that hypo-phosphorylation of the N2-Bus and hyper-phosphorylation of the PEVK domain can act complementary to elevate passive tension in failing human hearts. Differential changes in titin-domain phosphorylation may be important to fine-tune passive myocardial stiffness and diastolic function of the heart.
Inhibition of nucleoporin member Nup214 expression by miR-133b perturbs mitotic timing and leads to cell death
Authors: Sumana Bhattacharjya, Kumar Singha Roy, Abira Ganguly, Shreya Sarkar, Chinmay K Panda, Dibyendu Bhattacharyya, Nitai P Bhattacharyya, Susanta Roychoudhury
Journal: Molecular Cancer (2015)

Nucleoporins mediate nucleocytoplasmic exchange of macromolecules and several have been assigned active mitotic functions. Nucleoporins can participate in various mitotic functions like spindle assembly, kinetochore organisation and chromosome segregation- important for genome integrity. Pathways to genome integrity are frequently deregulated in cancer and many are regulated in part by microRNAs. Indeed, altered levels of numerous microRNAs have frequently been associated with tumorigenesis. Here, we unveil a microRNA-mediated regulation of the nucleoporin Nup214 and its downstream effect on genome integrity. Databases/bioinformatic tools such as miRBase, Oncomine and RNAhybrid predicted Nup214 as a miR-133b target. To validate this, we used luciferase reporter assays, Real-Time PCR and immuno-blotting. Flow cytometry and immuno-blots of mitotic markers were used to analyse cell cycle pattern upon thymidine synchronization and miR-133b treatment. Mitotic indices and chromosomal abnormalities were assessed by immuno-fluorescence for FITC-tagged phospho-H3 as well as video-microscopy for GFP-tagged histone H4. Annexin V/propidium iodide staining, caspase3/PARP cleavage and colony formation assays were done to investigate cell death upon either miR-133b transfection or NUP214 knockdown by siRNA. UPCI:SCC084, HCT116, HeLa-H4-pEGFP and HEK293 (human oral squamous cell carcinoma, colorectal, cervical carcinomas and embryonic kidney cell lines, respectively) were used. miR-133b and NUP214 expressions were validated in cancer cell lines and tissues by Real-Time PCR. Examination of head and neck tumour tissues and cancer cell lines revealed that Nup214 and miR-133b expressions are negatively correlated. In vitro, Nup214 was significantly downregulated by ectopic miR-133b. This downregulation elevated mitotic indices and delayed degradation of mitotic marker proteins cyclinB1 and cyclinA and dephosphorylation of H3. Moreover, this mitotic delay enhanced chromosomal abnormalities and apoptosis. We have identified NUP214, a member of the massive nuclear pore complex, as a novel miR-133b target. Thus, we have shown a hitherto unknown microRNA regulation of mitosis mediated by a member of the nucleoporin family. Based on observations, we also raise some hypotheses regarding transport-dependent/independent functions of Nup214 in this study. Our results hence attempt to explain why miR-133b is generally downregulated in tumours and lay out the potential for Nup214 as a therapeutic target in the treatment of cancer.
Screening for Bipolar Disorder in a Primary Care Practice
Authors: Amar K. Das
Journal: JAMA (2005)

Bipolar disorder consists of episodes of manic and depressive symptoms. Efforts to screen for depression in a primary care setting without assessment of past manic symptoms can lead to incorrect diagnosis and treatment of bipolar disorder.To screen for bipolar disorder in adult primary care patients and to examine its clinical presentation and effect on functioning.A systematic sample of 1157 patients between 18 and 70 years of age who were seeking primary care at an urban general medicine clinic serving a low-income population. The study was conducted between December 2001 and January 2003.Prevalence of bipolar disorder, its treatment and patient functioning. Study measures included the Mood Disorder Questionnaire, the PRIME-MD Patient Health Questionnaire, the Medical Outcomes Study 12-Item Short Form health survey, the Sheehan Disability Scale, data on past mental health treatments, and a review of medical records and International Classification of Diseases, Ninth Revision codes for each visit dating from 6 months prior to the screening day.The prevalence of receiving positive screening results for lifetime bipolar disorder was 9.8% (n = 112; 95% confidence interval, 8.0%-11.5%) and did not differ significantly by age, sex, or race/ethnicity. Eighty-one patients (72.3%) who screened positive for bipolar disorder sought professional help for their symptoms, but only 9 (8.4%) reported receiving a diagnosis of bipolar disorder. Seventy-five patients (68.2%) who screened positive for bipolar disorder had a current major depressive episode or an anxiety or substance use disorder. Of 112 patients, only 7 (6.5%) reported taking a mood-stabilizing agent in the past month. Primary care physicians recorded evidence of current depression in 47 patients (49.0%) who screened positive for bipolar disorder, but did not record a bipolar disorder diagnosis either in administrative billing or the medical record of any of these patients. Patients who screened positive for bipolar disorder reported worse health-related quality of life as well as increased social and family life impairment compared with those who screened negative.In an urban general medicine clinic, a positive screen for bipolar disorder appears to be common, clinically significant, and underrecognized. Because of the risks associated with treating bipolar disorder with antidepressant monotherapy, efforts are needed to educate primary care physicians about the screening, management, and pharmacotherapy of bipolar disorders.
Breast Cancer Classification: Time for a Change
Authors: Umberto Veronesi, Stefano Zurrida, Aron Goldhirsch, Nicole Rotmensz, Giuseppe Viale
Journal: Journal of Clinical Oncology (2009)

Patient: “Doctor, I am extremely worried about the mammotome report after microcalcifications were found on my mammogram. It says ductal carcinoma in situ. ‘Carcinoma’ means I could get metastases, doesn’t it and that I’ll probably have to have chemotherapy too?” Another patient: “Doctor I’m terrified. The report of my breast operation says ‘invasive carcinoma pT1N0M0.’ ‘Invasive’ means that I’ll get metastases, I’ll need chemotherapy, I’ll lose my hair. I am beside myself with the thought that I won’t see my children grow up.” These cries of distress, distilled from our experience in managing breast cancer, reflect legitimate concern that seems inflated by the way medical terms like carcinoma and infiltrating are understood. In fact, it seems to us that even oncologists use these words in misleading ways and that much of the blame for this lies with the International Union Against Cancer TNM (TNMUICC) classification of breast cancers. We would go further and suggest that this classification, which is now 60 years old, is in need of overhaul. Therefore, we wish to discuss our recently proposed Istituto Europeo di Oncologia TNM (TNMIEO) classification. 2
Incidence of HIV-Related Anal Cancer Remains Increased Despite Long-Term Combined Antiretroviral Treatment: Results From the French Hospital Database on HIV
Authors: Christophe Piketty, Hana Selinger-Leneman, Anne-Marie Bouvier, Aurelien Belot, Murielle Mary-Krause, Claudine Duvivier, Manuela Bonmarchand, Laurent Abramowitz, Dominique Costagliola, Sophie Grabar
Journal: Journal of Clinical Oncology (2012)

To study recent trends in the incidence of anal cancer in HIV-infected patients receiving long-term combined antiretroviral treatment (cART) compared with the general population.From the French Hospital Database on HIV, we identified 263 cases of invasive anal squamous cell carcinoma confirmed histologically between 1992 and 2008. We compared incidence rates of anal cancer across four calendar periods: 1992-1996 (pre-cART period), 1997-2000 (early cART period), and 2001-2004 and 2005-2008 (recent cART periods). Standardized incidence ratios (SIRs) were calculated by using general population incidence data from the French Network of Cancer Registries.In HIV-infected patients, the hazard ratio (HR) in the cART periods versus the pre-cART period was 2.5 (95% CI, 1.28 to 4.98). No difference was observed across the cART calendar periods (HR, 0.9; 95% CI, 0.6 to 1.3). In 2005-2008, HIV-infected patients compared with the general population had an excess risk of anal cancer, with SIRs of 109.8 (95% CI, 84.6 to 140.3), 49.2 (95% CI, 33.2 to 70.3), and 13.1 (95% CI, 6.8 to 22.8) for men who have sex with men (MSM), other men, and women, respectively. Among patients with CD4 cell counts above 500/μL for at least 2 years, SIRs were 67.5 (95% CI, 41.2 to 104.3) when the CD4 nadir was less than 200/μL for more than 2 years and 24.5 (95% CI, 17.1 to 34.1) when the CD4 nadir was more than 200/μL.Relative to that in the general population, the risk of anal cancer in HIV-infected patients is still extremely high, even in patients with high current CD4 cell counts. cART appears to have no preventive effect on anal cancer, particularly in MSM.
Intravascular filarial parasites elaborate cyclooxygenase-derived eicosanoids.
Authors: L X Liu, C N Serhan, P F Weller
Journal: The Journal of Experimental Medicine (1990)

The nematode parasites that cause human lymphatic filariasis survive for long periods in their vascular habitats despite continual exposure to host cells. Since prostanoids formed from arachidonic acid can modulate interactions among platelets, leukocytes, and endothelial cells, we examined whether intravascular nematode parasites can elaborate prostanoids. Microfilariae of Brugia malayi utilize exogenous and endogenous arachidonic acid to generate and release two predominant prostanoids, prostacyclin and prostaglandin E2. Filarial metabolism of host fatty acids to form these vasodilatory, antiaggregatory, and immunomodulatory eicosanoids provides a means by which these helminthic parasites may influence host immune and other cellular responses.
Abdominal Aortic Aneurysm
Authors: P.E. Norman, J.T. Powell
Journal: Circulation (2007)

M ost manifestations of cardiovascular disease are more common in men than in women.However, cardiovascular disease is the most common cause of death in women worldwide. 1Coronary heart disease in women has a worse outcome than in men, and this has attracted considerable attention in recent years, with calls for more gender-specific research. 1,2Abdominal aortic aneurysms (AAAs) also are less common in women than in men, and, as with coronary heart disease, there is evidence that women with AAA also have a worse prognosis.The present review addresses the epidemiology, development, natural history, management, and outcomes of AAA in women.
Toll-like receptor 4 in bone marrow-derived cells as well as tissue-resident cells participate in aggravating autoimmune destructive arthritis
Authors: Ben T van den Brand, Shahla Abdollahi-Roodsaz, Miranda B Bennink, Johan Bussink, Onno J Arntz, Wim B van den Berg, Fons A J van de Loo
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> A prominent role of Toll-like receptor 4 (TLR4) in arthritis is emerging. TLR4 is functional in immune cells and stromal cells. The aim was to investigate the involvement of TLR4 in bone marrow (BM)-derived and resident cells in arthritis. <h3>Methods</h3> Reciprocal sex-mismatched BM transplantation was performed between IL-1Ra<sup>−/−</sup>TLR4<sup>+/+</sup> and IL-1Ra<sup>−/−</sup>TLR4<sup>−/−</sup> double knockout animals in Balb/c background. Arthritis was assessed macroscopically and by histopathology. Immunity was evaluated by splenic cytokine production and flow cytometry in draining lymph node (DLN) cells. <h3>Results</h3> Arthritis progression was reduced to a similar extent in animals lacking TLR4 on BM-derived, resident cells or both. Histology revealed that joint inflammation was partially TLR4-dependent in either BM-derived or resident cells. TLR4 plays an additive role in BM-derived and resident cells in promoting cartilage erosion. By contrast, TLR4 was equally important in BM-derived and resident cells in mediating bone erosion. Systemically, TLR4 in both BM-derived and resident cells contributed to IL-17 production by splenic T-cells, whereas in the DLNs of arthritic joints this was not the case. Interestingly, in DLN, the dominant cells producing IL-17 were CD4 negative, and cell numbers were determined by TLR4 in the BM-derived cells. <h3>Conclusions</h3> TLR4 is necessary in both BM-derived and resident cells for full-blown joint swelling, inflammation and bone erosion. Furthermore, TLR4 on BM-derived and tissue-resident cells show an additive effect in cartilage destruction. Interestingly, TLR4 on BM-derived and tissue-resident cells are both required for IL-17 production in spleen, but only in BM-derived cells in DLN.