tbuckley/cabot-search huggingface dataset:
Mortality in asymptomatic vs. symptomatic patients surgically treated for non-small cell lung cancer (NSCLC)
Authors: Kirsten Riis Madsen, Uffe Bodtger
Journal: European Respiratory Journal (2013)

Introduction

Compared to incidentally found lung cancer, the presence of symptoms (eg. cough, haemoptysis, pain, weight loss) at diagnosis is associated with a 50% reduction in median survival. In surgically treated patients, it is unknown whether presence of symptoms has prognostic significance.

Aim

We wanted to ascertain if symptoms at time of NSCLC diagnosis lowered 12-months mortality after surgery.

Methods

Retrospective analysis of all patients with localised NSCLC referred from our department between 2009-2011 for intended curative surgery

Data on age, sex, tobacco pack years, Charlson’s index of co-morbidity, FEV1, former malignancy, symptoms at time of diagnosis, pre- and post-surgical TNM stage, and 12-months mortality post-surgery were recorded.

Results

130 patients were included: 51 (39%) asymptomatic and 79 symptomatic at NSCLC diagnosis with no differences concerning age, sex, tobacco pack years, or FEV1.

Former malignancy was significantly more prevalent among asymptomatic than symptomatic subjects (33 % vs. 11%), with insignificant differences in prevalence of other co-morbidities or in post-surgical TNM (82% vs 85% in stages IA-IIB).

12-months mortality was insignificantly higher in asymptomatic than symptomatic subjects (23% vs. 12%), and in patients with former malignancy compared to patients with no former cancer (17% vs. 16%).

Discussion

Symptoms at diagnosis per se appear unrelated to mortality in patients with NSCLC referred for surgery. Asymptomatic patients were more likely to have had prior malignancy. This suggests that incidentally found NSCLC was more likely when other medical conditions required thoracic imaging.
Nitric Oxide Inhalation Inhibits Platelet Aggregation and Platelet-Mediated Pulmonary Thrombosis in Rats
Authors: Zengxuan Nong, Marc Hoylaerts, Natasha Van Pelt, Désiré Collen, Stefan Janssens
Journal: Circulation Research (1997)

Endothelium-derived nitric oxide (NO) inhibits in vitro platelet aggregation via a cGMP-dependent mechanism. The effect of inhaled NO on platelet-mediated pulmonary thrombosis following intravenous thrombotic challenge with collagen was examined in rats and compared with the effect of G4120, a cyclic Arg-Gly-Asp-containing synthetic pentapeptide that binds to the platelet glycoprotein IIb/IIIa receptor. Intraplatelet cGMP dose-dependently increased from 39 +/- 6 fmol/10(8) platelets in control to 46 +/- 6, 68 +/- 13, and 81 +/- 13 fmol/10(8) platelets after inhalation with 20, 40, and 80 ppm NO, respectively (P < .05 for 40 and 80 ppm). Ex vivo platelet aggregation of platelet-rich plasma induced by 1 microgram/mL collagen was reduced from 75 +/- 4% in control rats to 22 +/- 10% and 20 +/- 7% in rats ventilated with 40 and 80 ppm NO, respectively, and to 30 +/- 9% in G4120-treated rats (each P < .05 versus control). Circulating platelet counts 3 minutes after collagen injection were significantly higher in the inhaled NO and G4120 groups compared with control rats (250,000 +/- 18,000 and 223,000 +/- 10,000/microL versus 160,000 +/- 18,000/microL, each P < .05). The rise in pulmonary arterial pressure after collagen injection was significantly reduced in NO- and G4120-treated rats (26 +/- 1 and 27 +/- 1 versus 32 +/- 1 mm Hg in control rats, each P < .05). The number of pulmonary resistance vessels containing platelet thrombi was significantly smaller after inhaled NO and G4120 treatment compared with control (56 +/- 3% and 50 +/- 3% versus 68 +/- 3%, respectively; P < .05). Thus, NO inhalation reduces in vivo activation of circulating platelets and platelet-rich thrombosis in thromboembolic pulmonary hypertension. Inhalation of NO may be useful in cardiovascular diseases associated with platelet activation.
Evolution in Regulatory Regions Rapidly Compensates the Cost of Nonoptimal Codon Usage
Authors: D. Amoros-Moya, S. Bedhomme, M. Hermann, I. G. Bravo
Journal: Molecular Biology and Evolution (2010)

The redundant genetic code contains synonymous codons, whose relative frequencies vary among species. Nonoptimal codon usage lowers gene translation efficiency, potentially leading to a fitness cost. This is particularly relevant for horizontal gene transfer, common among bacteria and a key player in antibiotic resistance propagation. By mimicking the horizontal transfer of an antibiotic resistance gene, we established that a nonoptimal codon usage renders Escherichia coli 10-20 times more sensitive to the antibiotic. After 350 generations of experimental evolution under antibiotic selection pressure, this cost was compensated through both in cis changes in the gene promoter and in trans changes in the host bacterial genome, without introducing mutations in the coding sequence of the resistance gene. Further, we have found experimental evidence for convergent molecular adaptive evolution. The high fitness cost of nonoptimal codon usage remains a minor obstacle to gene fixation upon horizontal transfer. Our results highlight the importance of rapid evolution of regulatory mechanisms in the adaptation to new environmental and genetic situations.
Highly efficient site-specific transgenesis in cancer cell lines
Authors: Iacovos P Michael, Claudio Monetti, Anthony C Chiu, Puzheng Zhang, Takeshi Baba, Koichiro Nishino, Siamak Agha-Mohammadi, Knut Woltjen, Hoon-Ki Sung, Andras Nagy
Journal: Molecular Cancer (2012)

Transgenes introduced into cancer cell lines serve as powerful tools for identification of genes involved in cancer. However, the random nature of genomic integration site of a transgene highly influences the fidelity, reliability and level of its expression. In order to alleviate this bottleneck, we characterized the potential utility of a novel PhiC31 integrase-mediated site-specific insertion system (PhiC31-IMSI) for introduction of transgenes into a pre-inserted docking site in the genome of cancer cells.According to this system, a "docking-site" was first randomly inserted into human cancer cell lines and clones with a single copy were selected. Subsequently, an "incoming" vector containing the gene of interest was specifically inserted in the docking-site using PhiC31.Using the Pc-3 and SKOV-3 cancer cell lines, we showed that transgene insertion is reproducible and reliable. Furthermore, the selection system ensured that all surviving stable transgenic lines harbored the correct integration site. We demonstrated that the expression levels of reporter genes, such as green fluorescent protein and luciferase, from the same locus were comparable among sister, isogenic clones. Using in vivo xenograft studies, we showed that the genetically altered cancer cell lines retain the properties of the parental line. To achieve temporal control of transgene expression, we coupled our insertion strategy with the doxycycline inducible system and demonstrated tight regulation of the expression of the antiangiogenic molecule sFlt-1-Fc in Pc-3 cells. Furthermore, we introduced the luciferase gene into the insertion cassette allowing for possible live imaging of cancer cells in transplantation assays. We also generated a series of Gateway cloning-compatible intermediate cassettes ready for high-throughput cloning of transgenes and demonstrated that PhiC31-IMSI can be achieved in a high throughput 96-well plate format.The novel PhiC31-IMSI system described in this study represents a powerful tool that can facilitate the characterization of cancer-related genes.
Friend Murine Leukemia Virus Resistance in Japanese Wild Mice: Possible Allelism With &lt;italic&gt;Fv-4&lt;/italic&gt; in FRG Mice&lt;xref ref-type="fn" rid="fn2"&gt;2&lt;/xref&gt;
Authors: S. Suzuki, K. Tsuji, K. Moriwaki
Journal: JNCI Journal of the National Cancer Institute (1981)

A dominant gene (Rm) for resistance to ecotropic murine leukemia virus was found in Japanese wild mice (Mn) and was similar to the FV-4 gene in inbred FRG mice. About one-fourth of the progeny of the cross (BALB/c x Mn) x (FRG x BALB/c) produced only resistant progeny when crossed to BALB/c mice, which indicated that Rm and Fv-4 are at the same chromosomal location. This evidence for allelism was confirmed by the finding that matings of BALB/c mice partially congenic for Rm or for Fv-4 yielded progeny that produced only resistant offspring when crossed to BALB/c mice.
Antimicrobial Peptides, Innate Immunity, and the Normally Sterile Urinary Tract
Authors: Michael Zasloff
Journal: Journal of the American Society of Nephrology (2007)

<h3>Abstract</h3> <h3>Background</h3> Group B Streptococcus (GBS) can cause invasive disease (iGBS) in young infants, typically presenting as sepsis or meningitis, and is also associated with stillbirth and preterm birth. GBS vaccines are under development, but their potential health impact and cost-effectiveness have not been assessed globally. <h3>Methods</h3> We assessed the health impact and value (using net monetary benefit, NMB, which measures both health and economic effects of vaccination into monetary units), of GBS maternal vaccination across 183 countries in 2020. Our analysis uses a decision-tree model, combining risks of GBS-related outcomes from a Bayesian disease burden model with estimates of GBS related costs and Quality-Adjusted Life Years (QALYs) lost. We assumed 80% vaccine efficacy against iGBS and stillbirth, following the WHO Preferred Product Characteristics, and coverage based on the proportion of pregnant women receiving at least four antenatal visits. One dose was assumed to cost $50 in high-income countries, $15 in upper-middle income countries, and $3.50 in low-/lower-middle income countries. We estimated NMB using alternative normative assumptions that may be adopted by policy makers. <h3>Findings</h3> Vaccinating pregnant women could avert 214,000 (95% uncertainty range 151,000 – 457,000) infant iGBS cases, 31,000 deaths (14,000 – 67,000), 21,000 (9,000 – 52,000) cases of neurodevelopmental impairment, and 23,000 (10,000 – 58,000) stillbirths. A vaccine effective against GBS-associated prematurity might also avert 172,000 (13,000 – 378,000) preterm births. Globally, a 1-dose vaccine programme could cost $1.7 billion but save $385 million in healthcare costs. Estimated global NMB ranged from $1.1 billion ($-0.2 – 3.8 billion) to $17 billion ($9.1 – 31 billion). <h3>Interpretation</h3> Maternal GBS vaccination could have a large impact on infant morbidity and mortality globally and at reasonable prices is likely to be cost-effective.
Inactivation of focal adhesion kinase in cardiomyocytes promotes eccentric cardiac hypertrophy and fibrosis in mice
Authors: X. Peng
Journal: Journal of Clinical Investigation (2005)

Focal adhesion kinase (FAK) is a cytoplasmic tyrosine kinase that plays a major role in integrin signaling pathways. Although cardiovascular defects were observed in FAK total KO mice, the embryonic lethality prevented investigation of FAK function in the hearts of adult animals. To circumvent these problems, we created mice in which FAK is selectively inactivated in cardiomyocytes (CFKO mice). We found that CFKO mice develop eccentric cardiac hypertrophy (normal LV wall thickness and increased left chamber dimension) upon stimulation with angiotensin II or pressure overload by transverse aortic constriction as measured by echocardiography. We also found increased heart/body weight ratios, elevated markers of cardiac hypertrophy, multifocal interstitial fibrosis, and increased collagen I and VI expression in CFKO mice compared with control littermates. Spontaneous cardiac chamber dilation and increased expression of hypertrophy markers were found in the older CFKO mice. Analysis of cardiomyocytes isolated from CFKO mice showed increased length but not width. The myocardium of CFKO mice exhibited disorganized myofibrils with increased nonmyofibrillar space filled with swelled mitochondria. Last, decreased tyrosine phosphorylation of FAK substrates p130Cas and paxillin were observed in CFKO mice compared with the control littermates. Together, these results provide strong evidence for a role of FAK in the regulation of heart hypertrophy in vivo.
Immunohistochemical and Molecular Analysis of Human Melanomas for Expression of the Human Cancer-Testis Antigens NY-ESO-1 and LAGE-1
Authors: Hilary A. Vaughan, Suzanne Svobodova, Duncan MacGregor, Sue Sturrock, Achim A. Jungbluth, Judy Browning, Ian D. Davis, Philip Parente, Yao-Tseng Chen, Elisabeth Stockert, Fiona St. Clair, Lloyd J. Old, Jonathan Cebon
Journal: Clinical Cancer Research (2004)

NY-ESO-1 and LAGE-1 are homologous cancer-testis antigens, which are expressed in many different cancers. It is essential to type tumors accurately to assess patient suitability for clinical trials which target these. This study evaluates typing strategies used to distinguish these two homologous but distinct antigens and to characterize and quantitate expression of each in clinical samples.We typed 120 malignant melanomas for the expression of NY-ESO-1 and LAGE-1 with immunohistochemistry, reverse transcription-PCR (RT-PCR), and quantitative real-time (qRT-PCR), which was also used to explore the relationship between NY-ESO-1 and LAGE expression.The two monoclonal antibodies ES121 and E978 had very similar immunohistochemistry reactivities. Both were specific for NY-ESO-1 because neither bound to homologous LAGE-1 peptides despite 84% overall amino acid homology. Of 120 melanomas tested by immunohistochemistry, NY-ESO-1 was expressed in >50% of cells in 23 melanomas (19%), between 11 and 50% cells in 15 (12.5%), <11% cells in 16 (13.5%), and negative in 66 (55%). Although specific for both antigens, the PCR methods did not provide this information about microheterogeneity. Polymorphisms in the LAGE-1 gene resulted in false negative LAGE-1 typing by qRT-PCR by inhibiting binding of oligonucleotide primers, thereby showing the exquisite specificity of qRT-PCR as a typing method.For NY-ESO-1 typing, immunohistochemistry compared favorably with the RT-PCR, with the added advantage of being able to characterize heterogeneity of antigen expression. Because neither mAb bound LAGE and because there was no coordinate expression LAGE and NY-ESO-1, separate typing for each is required.
Melatonin increases anagen hair rate in women with androgenetic alopecia or diffuse alopecia: results of a pilot randomized controlled trial
Authors: T.W. Fischer, G. Burmeister, H.W. Schmidt, P. Elsner
Journal: British Journal of Dermatology (2004)

Background In addition to the well‐known hormonal influences of testosterone and dihydrotestosterone on the hair cycle, melatonin has been reported to have a beneficial effect on hair growth in animals. The effect of melatonin on hair growth in humans has not been investigated so far.
Carboxyl-Terminal Src Kinase Homologous Kinase Negatively Regulates the Chemokine Receptor CXCR4 through YY1 and Impairs CXCR4/CXCL12 (SDF-1α)–Mediated Breast Cancer Cell Migration
Authors: Byeong-Chel Lee, Tae-Hee Lee, Radoslaw Zagozdzon, Shalom Avraham, Anny Usheva, Hava Karsenty Avraham
Journal: Cancer Research (2005)

Abstract Using microarray gene analysis, we found that carboxyl-terminal Src kinase homologous kinase (CHK) regulated the expression of the chemokine receptor, CXCR4. Northern blot and fluorescence-activated cell-sorting analyses showed that CHK down-regulated CXCR4 mRNA and protein levels, respectively. Mutated CHK, which contains a mutation within the ATP binding site of CHK, failed to inhibit CXCR4 expression, thus suggesting that CHK kinase activity is involved in the regulation of CXCR4. Results from gel shift analysis indicated that CHK regulates CXCR4 transcriptional activity by altering YY1 binding to the CXCR4 promoter. Whereas CHK had no significant effects on the expression of YY1, c-Myc, Max, and other YY1-binding proteins, CHK was found to modulate the YY1/c-Myc association. Furthermore, CHK inhibited CXCR4-positive breast cancer cell migration. Taken together, these studies show a novel mechanism by which CHK down-regulates CXCR4 through the YY1 transcription factor, leading to decreased CXCR4-mediated breast cancer cell motility and migration.
A Multistage Association Study Identifies a Breast Cancer Genetic Locus at<i>NCOA7</i>
Authors: Kathryn S.P. Higginbotham, Joan P. Breyer, Kevin M. Bradley, Peggy A. Schuyler, W. Dale Plummer, Marcia E. Freudenthal, Amy Trentham-Dietz, Polly A. Newcomb, Melinda E. Sanders, David L. Page, Fritz F. Parl, Kathleen M. Egan, William D. Dupont, Jeffrey R. Smith
Journal: Cancer Research (2011)

Abstract Estrogen metabolism and growth factor signaling pathway genes play key roles in breast cancer development. We evaluated associations between breast cancer and tagging single-nucleotide polymorphisms (SNP) of 107 candidate genes of these pathways using single allele- and haplotype-based tests. We first sought concordance of associations between two study populations: the Nashville Breast Cohort (NBC; 510 cases, 988 controls), and the Cancer Genetic Markers of Susceptibility (CGEMS) breast cancer study (1,145 cases, 1,142 controls). Findings across the two study populations were concordant at tagging SNPs of six genes, and at previously published SNPs of FGFR2. We sought further replication of results for EGFR, NCOA7, and FGFR2 in the independent Collaborative Breast Cancer Study (CBCS; 1,552 cases, 1,185 controls). Associations at NCOA7 and FGFR2 replicated across all three studies. The association at NCOA7 on 6q22.32, detected by a haplotype spanning the initial protein-coding exon (5′-rs9375411, rs11967627, rs549438, rs529858, rs490361, rs17708107-3′), has not been previously reported. The haplotype had a significant inverse association with breast cancer in each study [ORHet: 0.69 (NBC), 0.76 (CGEMS), 0.79 (CBCS)], and a meta-analysis ORHet of 0.75 (95% CI, 0.65–0.87, P = 1.4 × 10−4) in the combined study populations. The haplotype frequency was 0.07 among cases, and 0.09 among controls; homozygotes were infrequent and each ORHom was not significant. NCOA7 encodes a nuclear receptor coactivator that interacts with estrogen receptor α to modulate its activity. These observations provide consistent evidence that genetic variants at the NCOA7 locus may confer a reduced risk of breast cancer. Cancer Res; 71(11); 3881–8. ©2011 AACR.
The worldwide distribution of the VHL 598C&amp;gt;T mutation indicates a single founding event
Authors: Enli Liu, Melanie J. Percy, Christopher I. Amos, Yongli Guan, Sanjay Shete, David W. Stockton, Mary F. McMullin, Lydia A. Polyakova, Sonny O. Ang, Yves D. Pastore, Katerina Jedlickova, Terry R. J. Lappin, Victor Gordeuk, Josef T. Prchal
Journal: Blood (2003)
Assessment of impairment/disability due to occupational asthma through a multidimensional approach
Authors: M-R. Yacoub, K. Lavoie, G. Lacoste, S. Daigle, J. L'Archeveque, H. Ghezzo, C. Lemiere, J-L. Malo
Journal: European Respiratory Journal (2006)

Subjects with occupational asthma (OA) are often left with permanent sequelae after removal from exposure, and assessing their impairment/disability should utilise various tools. The aim of the present study was to examine whether: 1) assessment of inflammation in induced sputum is relevant to impairment; and 2) use of questionnaires on quality of life and psychological factors can be useful for the evaluation of disability. In total, 40 subjects were prospectively assessed for permanent impairment/disability due to OA 2 yrs after cessation of exposure. Impairment was assessed as follows: 1) need for asthma medication; 2) asthma severity; 3) airway calibre and responsiveness; and 4) degree of inflammation in induced sputum. Disability was assessed according to quality of life and psychological distress. There was a significant improvement in airway responsiveness and inflammation from diagnosis to the present assessment. Sputum eosinophils ≥2% and neutrophils &gt;60% were present in eight (20%) and 12 (30%) out of all subjects, respectively, one or the other feature being the only abnormalities in 15% of subjects. Quality of life was moderately affected and there was a prevalence of depression and anxiety close to 50%. In the assessment of subjects with occupational asthma, information on airway inflammation and psychological impacts are relevant to the assessment of impairment/disability, although these findings need further investigation.
Direct Child Observation in Psychiatry Residency Training
Authors: JERRY M. WIENER, ROBERT MICHELS
Journal: American Journal of Psychiatry (1971)

Direct observation of normal children at various stages of development was incorporated into a psychiatry residency program. This experience helps to compensate for the resident's limited contact with normal children and complement his study of personality development and child psychopathology. Three observational experiences are described, followed by typical vignettes. The authors feel that analogous programs could be developed for medical students, pediatric residents, and other health professionals.
Cell-mediated mitogenic response induced by leukoagglutinin and Lens culinaris lectin in mouse lymphocytes.
Authors: K Ozato, J Cebra, J D Ebert
Journal: The Journal of Experimental Medicine (1977)

The proliferative response of mouse lymphocytes to syngeneic cellular stimulation upon membrane modification with lectins was studied. Brief pretreatment of stimulator cells (mitomycin-C-treated spleen cells) followed by mixed culture with syngeneic cortisone-resistant thymocytes resulted in a significant proliferative response in the thymocytes. This effect was not due to a soluble mediator and was similar to the mitogenic response after Con A-induced membrane modification reported previously. Because of its general characteristics, we refer to this response as cell-mediated mitogenic response (CMMR). Cell contact between stimulator and responder cells was necessary but not sufficient for the induction of the response. The lectins that generated CMMR were T-cell mitogens. CMMR was generated in all the syngeneic combinations tested and even in allogeneic combinations. No detectable cytotoxic activity towards syngeneic targets cells was produced after CMMR. Moreover, CMMR in allogeneic combinations led to the suppression of the generation of specific cytotoxic lymphocytes. Population analysis with antibodies against T or B cells, nylon wool fractionation of stimulator cells, and tests with peritoneal macrophages and with spleen cells from athymic mice revealed that CMMR depends predominantly on the interaction between responder T cells and stimulator Ig-positive lymphocytes.
Prevalence and associations of an abnormal ankle-brachial index in systemic lupus erythematosus: a pilot study
Authors: A Theodoridou
Journal: Annals of the Rheumatic Diseases (2003)

Accelerated atheroma is a well recognised complication of systemic lupus erythematosus (SLE). Its aetiology is multifactorial and several methods may be used to detect early signs of atheroma.Patients aged </=55 years were screened using the ankle-brachial index (ABI). Ninety one patients aged </=55 years and fulfilling the revised American College of Rheumatology criteria for SLE were studied. The ABI was measured using a contour wrapped 12 cm cuff attached to a mercury sphygmomanometer and an 8 MHz Doppler probe in the arms and legs; a ratio of <1 was considered abnormal.The mean (SD) age of the patients was 39.0 (9.2) years. Of the 91 patients studied, 34 (37%) had an abnormal ABI. Only one patient was mildly symptomatic. Abnormal ABI correlated with age but not with disease duration, cumulative steroid dosage, ECLAM score, or any other traditional risk factors for atherosclerosis. In comparison with population studies, the prevalence of an ABI<1 in the patients with SLE with a mean age of 39 years was similar to that in adults aged over 80.In this pilot study, patients with SLE with a mean age of 39 years had a high prevalence of an abnormal ABI. The ABI is a simple non-invasive tool for the early detection of accelerated atheroma in SLE.