tbuckley/cabot-search huggingface dataset:
Smoking Is Associated With Altered Endothelial-Derived Fibrinolytic and Antithrombotic Factors
Authors: Rajat S. Barua, John A. Ambrose, Dhanonjoy C. Saha, Lesley-Jane Eales-Reynolds
Journal: Circulation (2002)

Background— Data about the effects of smoking on thrombo-hemostatic factors (tissue factor [TF] and tissue factor pathway inhibitor [TFPI-1]) are limited and on fibrinolytic factors (tissue plasminogen activator [t-PA] and plasminogen activator inhibitor-1 [PAI-1]) are debatable. The present study investigated the smoking-related, endothelial cell (EC)–specific responses for these factors and their relation to nitric oxide (NO) production in vitro. Methods and Results— Serum from 8 nonsmokers and 15 smokers were incubated with confluent (≈85%) human umbilical vein endothelial cells (HUVECs) in 24-well tissue-culture plates for 12 hours. After the incubation, basal NO, t-PA, PAI-1, TF, TFPI-1 production, and substance P (SP)–stimulated NO, t-PA, and PAI-1 production were determined. HUVECs treated with smokers’ serum showed lower basal ( P &lt;0.02) and SP-stimulated ( P =0.059) t-PA production but similar basal and stimulated PAI-1 production ( P =0.9 and P =0.6) compared with nonsmokers. Basal t-PA/PAI-1 molar ratio was significantly reduced in smokers ( P &lt;0.005). TFPI-1 level in the cell culture supernatant was also significantly lower in smokers compared with the nonsmoker group ( P &lt;0.05) with no difference in TF level between both groups ( P =0.5). As previously reported, both basal ( P &lt;0.001) and SP-stimulated ( P &lt;0.05) NO production were significantly reduced in smokers. Basal TFPI-1 in culture correlated positively with basal NO production ( r =0.42, P =0.04) and negatively with serum cotinine level ( r =−0.6, P =0.01). Conclusions— These results indicate that cigarette smoking is associated with alterations in EC-derived fibrinolytic (t-PA) and antithrombotic (TFPI-1) factors. To our knowledge, this is the first demonstration that EC-derived TFPI is affected by smoking and endogenous NO or that the degree of smoke exposure may influence TFPI levels in an EC milieu.
Phase II multicenter study of larotaxel (XRP9881), a novel taxoid, in patients with metastatic breast cancer who previously received taxane-based therapy
Authors: V. Diéras, S. Limentani, G. Romieu, M. Tubiana-Hulin, A. Lortholary, P. Kaufman, V. Girre, M. Besenval, V. Valero
Journal: Annals of Oncology (2008)
Effectiveness of Radiation Therapy for Older Women With Early Breast Cancer
Authors: Benjamin D. Smith, Cary P. Gross, Grace L. Smith, Deron H. Galusha, Justin E. Bekelman, Bruce G. Haffty
Journal: JNCI Journal of the National Cancer Institute (2006)

Background: Recent clinical trials have questioned the necessity of breast radiation therapy for older women with early breast cancer. However, the effectiveness of radiation therapy for older women in the community setting has not been addressed. Methods: We used the Surveillance, Epidemiology, and End Results (SEER)–Medicare database from January 1, 1992, through December 31, 1999, to identify 8724 women aged 70 years or older treated with conservative surgery for small, lymph node–negative, estrogen receptor–positive (or unknown receptor status) breast cancer. We used a proportional hazards model to test whether radiation therapy was associated with a lower risk of a combined outcome, defined as a second ipsilateral breast cancer reported by SEER and/or a subsequent mastectomy reported by Medicare claims. All statistical tests were two-sided. Results: Radiation therapy, compared with no radiation therapy, was associated with a lower risk of the combined outcome (hazard ratio = 0.19, 95% confidence interval = 0.14 to 0.28). Radiation therapy was associated with an absolute risk reduction of 4.0 events per 100 women at 5 years (i.e., from 5.1 events without radiation therapy to 1.1 with radiation therapy) and 5.7 events per 100 persons at 8 years (i.e., from 8.0 events without radiation therapy to 2.3 with radiation therapy) ( P <.001, log-rank test). Radiation therapy was most likely to benefit those aged 70–79 years without comorbidity (number needed to treat [NNT] to prevent one event = 21 to 22 patients) and was least likely to benefit those aged 80 years or older with moderate to severe comorbidity (NNT = 61 to 125 patients). Conclusion: For older women with early breast cancer, radiation therapy was associated with a lower risk of a second ipsilateral breast cancer and subsequent mastectomy. Patients aged 70–79 years with minimal comorbidity were the most likely to benefit, and older patients with substantial comorbidity were least likely to benefit.
Single nucleotide polymorphisms and outcome in docetaxel–cisplatin-treated advanced non-small-cell lung cancer
Authors: D. Isla, C. Sarries, R. Rosell, G. Alonso, M. Domine, M. Taron, G. Lopez-Vivanco, C. Camps, M. Botia, L. Nuñez, M. Sanchez-Ronco, J.J. Sanchez, M. Lopez-Brea, I. Barneto, A. Paredes, B. Medina, A. Artal, P. Lianes
Journal: Annals of Oncology (2004)

Platinum-based doublets are the standard chemotherapy for advanced non-small-cell lung cancer (NSCLC). Excision-repair cross-complementing 1 (ERCC1), xeroderma pigmentosum group D (XPD) and ribonucleotide reductase subunit M1 (RRM1) are essential to the repair of cisplatin DNA adducts. Multidrug resistance 1 (MDR1) has been related to antimicrotubule resistance. We assessed whether single nucleotide polymorphisms (SNPs) in ERCC1, XPD, RRM1 and MDR1, and ERCC1 mRNA expression, predicted survival in docetaxel-cisplatin-treated stage IV NSCLC patients.Using the TaqMan 5' nuclease assay, we examined ERCC1 118, XPD 751 and 312, RRM1 -37C/A, and MDR1 C3435T SNPs in peripheral blood lymphocytes (PBLs) obtained from 62 docetaxel-cisplatin-treated advanced NSCLC patients. ERCC1 expression was measured in RNA isolated from PBLs using real-time reverse transcriptase PCR.Overall median survival was 10.26 months. Median survival was 9.67 months for 34 patients with ERCC1 118 C/T, 9.74 months for 17 patients with T/T, and not reached for 11 patients with C/C (P=0.04). Similar significant differences in time to progression were observed according to ERCC1 118 genotype (P=0.03). No other significant differences were observed.Patients homozygous for the ERCC1 118 C allele demonstrated a significantly better survival. ERCC1 SNP assessment could be an important component of tailored chemotherapy trials.
Receptor-Targeted Nanoparticles for <i>In vivo</i> Imaging of Breast Cancer
Authors: Lily Yang, Xiang-Hong Peng, Y. Andrew Wang, Xiaoxia Wang, Zehong Cao, Chunchun Ni, Prasanthi Karna, Xinjian Zhang, William C. Wood, Xiaohu Gao, Shuming Nie, Hui Mao
Journal: Clinical Cancer Research (2009)

Cell-surface receptor-targeted magnetic iron oxide nanoparticles provide molecular magnetic resonance imaging contrast agents for improving specificity of the detection of human cancer.The present study reports the development of a novel targeted iron oxide nanoparticle using a recombinant peptide containing the amino-terminal fragment of urokinase-type plasminogen activator (uPA) conjugated to magnetic iron oxide nanoparticles amino-terminal fragment conjugated-iron oxide (ATF-IO). This nanoparticle targets uPA receptor, which is overexpressed in breast cancer tissues.ATF-IO nanoparticles are able to specifically bind to and be internalized by uPA receptor-expressing tumor cells. Systemic delivery of ATF-IO nanoparticles into mice bearing s.c. and i.p. mammary tumors leads to the accumulation of the particles in tumors, generating a strong magnetic resonance imaging contrast detectable by a clinical magnetic resonance imaging scanner at a field strength of 3 tesla. Target specificity of ATF-IO nanoparticles showed by in vivo magnetic resonance imaging is further confirmed by near-IR fluorescence imaging of the mammary tumors using near-IR dye-labeled amino-terminal fragment peptides conjugated to iron oxide nanoparticles. Furthermore, mice administered ATF-IO nanoparticles exhibit lower uptake of the particles in the liver and spleen compared with those receiving nontargeted iron oxide nanoparticles.Our results suggest that uPA receptor-targeted ATF-IO nanoparticles have potential as molecularly targeted, dual modality imaging agents for in vivo imaging of breast cancer.
New Strategies in Muscle-Invasive Bladder Cancer: On the Road to Personalized Medicine
Authors: Jay B. Shah, David J. McConkey, Colin P.N. Dinney
Journal: Clinical Cancer Research (2011)

Bladder cancer remains one of the most deadly and expensive diseases affecting modern society. The options currently available to patients with muscle-invasive bladder cancer have remained essentially unchanged for the last generation. As the roles for surgery and chemotherapy in the management of this lethal disease have become better defined, so too have the limitations of these two treatment modalities. Despite the lack of groundbreaking clinical advances over the past two decades, recent years have witnessed a notable increase in the amount of promising preclinical and early translational research that will greatly improve our understanding of the molecular underpinnings of bladder cancer. If this momentum in bladder cancer research continues to build, it is likely that in the next 5 to 10 years we will be able to achieve our goal of bringing bladder cancer treatment into the age of personalized medicine.
Are amoxycillin and folate inhibitors as effective as other antibiotics for acute sinusitis? A meta-analysis
Authors: S. D de Ferranti, J. P A Ioannidis, J. Lau, W. V Anninger, M. Barza
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objectives:</b> To examine whether antibiotics are indicated in treating uncomplicated acute sinusitis and, if so, whether newer and more expensive antibiotics with broad spectra of antimicrobial activity are more effective than amoxycillin or folate inhibitors. <b>Design:</b> Meta-analysis of randomised trials. <b>Setting:</b> Outpatient clinics. <b>Subjects:</b> 2717 patients with acute sinusitis or acute exacerbation of chronic sinusitis from 27 trials. <b>Interventions:</b> Any antibiotic versus placebo; amoxycillin or folate inhibitors versus newer, more expensive antibiotics. <b>Main outcome measurements:</b> Clinical failures and cures. <b>Results:</b> Compared with placebo, antibiotics decreased the incidence of clinical failures by half (risk ratio 0.54 (95% confidence interval 0.37 to 0.79)). Risk of clinical failure among 1553 randomised patients was not meaningfully decreased with more expensive antibiotics as compared with amoxycillin (risk ratio 0.86 (0.62 to 1.19); risk difference 0.9 fewer failures per 100 patients (1.4 more failures to 3.1 fewer failures per 100 patients)). The results were similar for other antibiotics versus folate inhibitors (risk ratio 1.01 (0.52 to 1.97)), but data were sparse (n=410) and of low quality. <b>Conclusions:</b> Amoxycillin and folate inhibitors are essentially as effective as more expensive antibiotics for the initial treatment of uncomplicated acute sinusitis. Small differences in efficacy may exist, but are unlikely to be clinically important.
Demographic effects of the introduction of steroid contraception in developed countries
Authors: Henri Leridon
Journal: Human Reproduction Update (2006)

Abstract The use of the contraceptive pill increased very rapidly in the 1970s in many developed countries, and fertility almost simultaneously started to decline. We discuss here the possibility of a causal link between these two major changes. We first provide evidence for a relationship between the spread of oral contraceptive use and the change in fertility in many European countries over the last three or four decades. The situation of specific countries is examined more in depth on the basis of available literature. We then review the various theories attempting to explain these trends and see how the family planning variables are treated in these approaches. At the country level, the conclusion is unambiguous: within individual countries, there is no systematic negative correlation between fertility and contraceptive pill use. The development of hormonal contraception cannot be considered as responsible for either starting or the size of the fertility decline. A more subtle chain of causality must be considered, but there is no agreement on a general theory of fertility changes. Most authors, however, agree that the diffusion of modern contraception has certainly contributed to the reduction in the number of unwanted pregnancies and has also facilitated and favoured the adoption of new (more restrictive) norms for the ideal family size.
Resistance against Staphylococcus aureus
Authors: S. Mudd
Journal: JAMA (1971)

Protection against the invasiveness of<i>Staphylococcus aureus</i>has been sought for many decades through use of staphylococcal vaccines. The assumption has been that circulating antibodies could be called up to promote phagocytosis and killing of<i>Staph aureus</i>, in analogy with the effects of antibodies against streptococci and pneumococci. Results have been disappointing, for the reason that the underlying assumption is not true. Explanation lies in the peculiar immunochemistry of the surface of the staphylococcal cell. Fortunately, however, the special attributes of<i>Staph aureus</i>do offer promise in the guise of cell-mediated resistance. A high proportion of human subjects are colonized or infected with<i>Staph aureus</i>and, in consequence, have allergy, characterized by delayed-type hypersensitivity to<i>Staph aureus</i>. Cell-mediated resistance can be elicited by appropriate administration of staphylococcal antigens; such antigens are licensed and in use.
Pragmatic randomized controlled trial of long‐term psychoanalytic psychotherapy for treatment‐resistant depression: the Tavistock Adult Depression Study (TADS)
Authors: Peter Fonagy, Felicitas Rost, Jo‐anne Carlyle, Susan McPherson, Rachel Thomas, R.M. Pasco Fearon, David Goldberg, David Taylor
Journal: World Psychiatry (2015)

This pragmatic randomized controlled trial tested the effectiveness of long‐term psychoanalytic psychotherapy (LTPP) as an adjunct to treatment‐as‐usual according to UK national guidelines (TAU), compared to TAU alone, in patients with long‐standing major depression who had failed at least two different treatments and were considered to have treatment‐resistant depression. Patients (N=129) were recruited from primary care and randomly allocated to the two treatment conditions. They were assessed at 6‐monthly intervals during the 18 months of treatment and at 24, 30 and 42 months during follow‐up. The primary outcome measure was the 17‐item version of the Hamilton Depression Rating Scale (HDRS‐17), with complete remission defined as a HDRS‐17 score ≤8, and partial remission defined as a HDRS‐17 score ≤12. Secondary outcome measures included self‐reported depression as assessed by the Beck Depression Inventory ‐ II, social functioning as evaluated by the Global Assessment of Functioning, subjective wellbeing as rated by the Clinical Outcomes in Routine Evaluation ‐ Outcome Measure, and satisfaction with general activities as assessed by the Quality of Life Enjoyment and Satisfaction Questionnaire. Complete remission was infrequent in both groups at the end of treatment (9.4% in the LTPP group vs. 6.5% in the control group) as well as at 42‐month follow‐up (14.9% vs. 4.4%). Partial remission was not significantly more likely in the LTPP than in the control group at the end of treatment (32.1% vs. 23.9%, p=0.37), but significant differences emerged during follow‐up (24 months: 38.8% vs. 19.2%, p=0.03; 30 months: 34.7% vs. 12.2%, p=0.008; 42 months: 30.0% vs. 4.4%, p=0.001). Both observer‐based and self‐reported depression scores showed steeper declines in the LTPP group, alongside greater improvements on measures of social adjustment. These data suggest that LTPP can be useful in improving the long‐term outcome of treatment‐resistant depression. End‐of‐treatment evaluations or short follow‐ups may miss the emergence of delayed therapeutic benefit.
Lipoprotein Abnormalities in Human Genetic CD36 Deficiency Associated With Insulin Resistance and Abnormal Fatty Acid Metabolism
Authors: Takahiro Kuwasako, Ken-ichi Hirano, Naohiko Sakai, Masato Ishigami, Hisatoyo Hiraoka, Mohamed Janabi Yakub, Keiko Yamauchi-Takihara, Shizuya Yamashita, Yuji Matsuzawa
Journal: Diabetes Care (2003)

CD36 is an 88-kDa membranous protein with multiple relevant function that is widely expressed in human tissues (1). Because we and others (2) found human genetic deficiency of this molecule, we have elucidated the molecular bases and pathophysiology. We have reported that the human deficiency may be associated with insulin resistance (3) and abnormal dynamics of long-chain fatty acid (LCFA) (4). The aim of the present study was to further characterize lipid and lipoprotein metabolism in the human genetic CD36 deficiency, especially focusing on postprandial …
Liraglutide versus sitagliptin for patients with type 2 diabetes who did not have adequate glycaemic control with metformin: a 26-week, randomised, parallel-group, open-label trial
Authors: Richard E Pratley, Michael Nauck, Timothy Bailey, Eduard Montanya, Robert Cuddihy, Sebastiano Filetti, Anne Bloch Thomsen, Rie Elvang Søndergaard, Melanie Davies
Journal: The Lancet (2010)
HMGA1 Protein Overexpression in Human Breast Carcinomas
Authors: Gennaro Chiappetta, Gerardo Botti, Mario Monaco, Rosa Pasquinelli, Francesca Pentimalli, Maurizio Di Bonito, Giuseppe D’Aiuto, Monica Fedele, Rodolfo Iuliano, Emiliano A. Palmieri, Giovanna Maria Pierantoni, Vincenzo Giancotti, Alfredo Fusco
Journal: Clinical Cancer Research (2004)

Abstract We measured, by immunohistochemistry, HMGA1 protein expression in 212 breast tissue specimens: 6 normal samples, 28 hyperplastic lesions (13 with cellular atypia), 11 fibroadenomas, 10 in situ ductal carcinomas, 144 ductal carcinomas, and 13 lobular carcinomas. HMGA1 was not expressed in normal breast tissue; HMGA1 staining was intense in 40% of hyperplastic lesions with cellular atypia and in 60% of ductal carcinomas and weak in fibroadenomas and in hyperplastic lesions without cellular atypia. Because HMGA1 expression was similar among ductal breast carcinomas with different histologic grading, we evaluated the association between HMGA1 expression and that of other markers of breast carcinoma invasion (estrogen and progesterone receptors, Ki-67 antigen, and ErbB2) in 21 cases of grade 3 breast ductal carcinomas and 7 cases of breast lobular carcinomas. We found that HMGA1 expression tended to be associated only with c-erbB-2 expression (Spearman rho: 0.36; P = 0.065). Taken together, these results suggest that HMGA1 expression might be a novel indicator for the diagnosis and prognosis of human breast cancer.
Subclinical gut inflammation in spondyloarthritis is associated with a pro-angiogenic intestinal mucosal phenotype
Authors: P. Hindryckx, D. Laukens, G. Serry, L. Van Praet, C. Cuvelier, H. Mielants, H. Peeters, D. Elewaut, M. De Vos
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background</h3> Vascular endothelial growth factor (VEGF-A) and placental growth factor (PlGF) are major regulators of pathological angiogenesis, which is a prominent feature of both Crohn9s disease (CD) and peripheral synovitis in spondyloarthritis. <h3>Objective</h3> To investigate the presence of VEGF-A and PlGF in the gut of spondyloarthritis patients and to link this finding with subclinical gut inflammation in these patients. <h3>Methods</h3> Intestinal biopsies from healthy controls, CD patients, spondyloarthritis patients with or without subclinical gut inflammation and rheumatoid arthritis (RA) patients were stained for VEGF-A, PlGF, CD31 and vascular cell adhesion molecule 1 (VCAM-1) and digitally analysed. <h3>Results</h3> Spondyloarthritis patients with subclinical gut inflammation had markedly increased intestinal VEGF-A expression (p&lt;0.001), mucosal vascularisation (p&lt;0.001) and VCAM-1 expression (p&lt;0.01) compared with healthy controls and RA patients, which, unlike in CD patients, was also seen when the gut inflammation was in a quiescent state. PlGF expression was highly increased in the subclinically inflamed gut of spondyloarthritis (p&lt;0.01 compared with healthy controls), but not at all in CD. <h3>Conclusion</h3> A pro-angiogenic intestinal phenotype is observed in spondyloarthritis patients with quiescent chronic gut inflammation. This favours an environment for enhanced trafficking of immune cells in this subpopulation.
Plaque Rupture Causing Spontaneous Coronary Artery Dissection in a Patient With Acute Myocardial Infarction
Authors: Naoya Ichiba, Kenei Shimada, Makoto Hirose, Yoshiki Kobayashi, Kumiko Hirata, Yuji Sakanoue, Iku Toda, Masakazu Teragaki, Kaname Akioka, Kazuhide Takeuchi, Junichi Yoshikawa
Journal: Circulation (2000)
In vivo transfection of hepatitis C virus complementary DNA into rodent liver by asialoglycoprotein receptor mediated gene delivery
Authors: Masato Yamamoto, Norio Hayashi, Yasuhide Miyamoto, Tetsuo Takehara, Eiji Mita, Makoto Seki, Hideyuki Fusamoto, Takenobu Kamada
Journal: Hepatology (1995)

An in vivo model of hepatitis C virus (HCV) infection is needed to enable investigation of the mechanism of the liver injury that it causes. In this study, we used asialoglycoprotein receptor mediated gene delivery to obtain expression of the complementary DNA (cDNA) coding the core and part of the envelope 1 protein of HCV because selective delivery to the hepatocytes has been reported to be attained with this method. The optimum carrier-DNA ratio was examined using in vitro transfection and found to be important for the efficiency of this method. In transfection in vivo, microautoradiographical examination showed that the transfected plasmids were delivered selectively to the liver parenchymal cells. To obtain an immunohistochemically detectable level of protein expression in rodent liver, some modifications for increasing the in vivo transfection efficiency were performed; a lysosomal enzyme inhibitor, chloroquine, was used and the administration route of the carrier-DNA complex was changed from the tail vein to the portal vein. On the bases of these results, in vivo transfection with expression vector of HCV core/E1 region was performed. In rat liver transfected by intraportal injection with chloroquine, the transcript RNA and the core protein were detected. These results indicated that the HCV core/E1 expression vector was not merely delivered but also successfully expressed in the liver using asialoglycoprotein receptor mediated gene delivery. The number of the HCV core expressing cells in the transfected liver was similar to that in patients with hepatitis C. These in vivo transfected animals should be useful for investigating the role of this region in the liver injury caused by HCV.
Exome sequencing identifies putative drivers of progression of transient myeloproliferative disorder to AMKL in infants with Down syndrome
Authors: Sergey I. Nikolaev, Federico Santoni, Anne Vannier, Emilie Falconnet, Emanuela Giarin, Giuseppe Basso, Alexander Hoischen, Joris A. Veltman, Jurgen Groet, Dean Nizetic, Stylianos E. Antonarakis
Journal: Blood (2013)
Imitation, emulation, and the transmission of culture
Authors: Andrew Whiten
Journal: Behavioral and Brain Sciences (2008)

Abstract Three related issues are addressed. First, Hurley treats emulation and imitation as a straightforward dichotomy with emulation emerging first. Recent conceptual analyses and “ghost” chimpanzee experiments challenge this. Second, other recent chimpanzee experiments reveal high-fidelity social transmission, questioning whether copying fidelity is the brake on cumulative culture. Finally, other cognitive processes such as pretence need to be integrated.