tbuckley/cabot-search huggingface dataset:
Common Germline Genetic Variation in Antioxidant Defense Genes and Survival After Diagnosis of Breast Cancer
Authors: Miriam Udler, Ana-Teresa Maia, Arancha Cebrian, Clement Brown, David Greenberg, Mitul Shah, Carlos Caldas, Alison Dunning, Douglas Easton, Bruce Ponder, Paul Pharoah
Journal: Journal of Clinical Oncology (2007)

Purpose The prognosis of breast cancer varies considerably among individuals, and inherited genetic factors may help explain this variability. Of particular interest are genes involved in defense against reactive oxygen species (ROS) because ROS are thought to cause DNA damage and contribute to the pathogenesis of cancer. Patients and Methods We examined associations between 54 polymorphisms that tag the known common variants (minor allele frequency &gt; 0.05) in 10 genes involved in oxidative damage repair (CAT, SOD1, SOD2, GPX1, GPX4, GSR, TXN, TXN2, TXNRD1, and TXNRD2) and survival in 4,470 women with breast cancer. Results Two single nucleotide polymorphisms (SNPs) in GPX4 ( rs713041 and rs757229 ) were associated with all-cause mortality even after adjusting for multiple hypothesis testing (adjusted P = .0041 and P = .0035). These SNPs are correlated with each other (r 2 = 0.61). GPX4 rs713041 is located near the selenocysteine insertion sequence element in the GPX4 3′ untranslated region, and the rare allele of this SNP is associated with an increased risk of death, with a hazard ratio of 1.27 per rare allele carried (95% CI, 1.13 to 11.43). This effect was not attenuated after adjusting for tumor stage, grade, or estrogen receptor status. We found that the common allele is preferentially expressed in normal lymphocytes, normal breast, and breast tumors compared with the rare allele, but there were no differences in total levels of GPX4 mRNA across genotypes. Conclusion These data provide strong support for the hypothesis that common variation in GPX4 is associated with prognosis after a diagnosis of breast cancer.
URINARY OUTPUT OF ADRENALINE, NORADRENALINE, AND 3-METHOXY-4-HYDROXYMANDELIC ACID FOLLOWING CENTRIFUGATION AND ANTICIPATION OF CENTRIFUGATION *
Authors: McC. Goodall, M. L. Berman
Journal: Journal of Clinical Investigation (1960)

It has been shown that various forms of stress, i.e., thermal burn (1), muscular exercise (2), centrifugation (3-5), trauma (6) and so forth activate the sympatho-adrenal system and that this activation is manifested by an increase in the urinary output of adrenaline and noradrenaline. Furthermore, it has been demonstrated in the normal human that 3-methoxy-4-hydroxymandelic acid is one of the principal metabolic products of both adrenaline and noradrenaline (7-10). Hitherto, there have been no stress experiments correlating the urinary output of adrenaline and noradrenaline with that of 3-methoxy-4-hydroxymandelic acid. The experiments herein described not only demonstrate such a correlation but also show the effect of centrifugation and anticipation of centrifugation upon the urinary output of adrenaline, noradrenaline, and 3-methoxy-4-hydroxymandelic acid.
Effects of nanoparticles on lung damage in humans
Authors: K. Inoue, H. Takano
Journal: European Respiratory Journal (2009)

We read with great interest the article in the European Respiratory Journal by JORENS et al.[1] on the different types of nonthrombotic pulmonary embolism.Among them, hydatid disease is of major importance as it is endemic in sheep-raising regions worldwide.We wish, therefore, to outline the management of metastatic pulmonary hydatidosis secondary to a primary hydatid cyst located in the liver according to our experience of six cases.
Management of Protein and Energy Intake in Dialysis Patients
Authors: MARSHA WOLFSON
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Malnutrition is not uncommon in patients with end-stage renal disease treated with maintenance dialysis. The presence of several abnormal parameters of nutritional status are reported to be predictive of poorer outcomes in these patients, compared to dialysis patients without evidence of malnutrition. This article describes methods that may be used to recognize the presence of malnutrition in end-stage renal disease patients and the management of protein and energy intake. Whether the correction of malnutrition will improve outcomes, such as morbidity and mortality, is unknown.
Second-generation shRNA libraries covering the mouse and human genomes
Authors: Jose M Silva, Mamie Z Li, Ken Chang, Wei Ge, Michael C Golding, Richard J Rickles, Despina Siolas, Guang Hu, Patrick J Paddison, Michael R Schlabach, Nihar Sheth, Jeff Bradshaw, Julia Burchard, Amit Kulkarni, Guy Cavet, Ravi Sachidanandam, W Richard McCombie, Michele A Cleary, Stephen J Elledge, Gregory J Hannon
Journal: Nature Genetics (2005)
Human Schwannomas Express Activated Platelet-Derived Growth Factor Receptors and c-kit and Are Growth Inhibited by Gleevec (Imatinib Mesylate)
Authors: Joydeep Mukherjee, Deepak Kamnasaran, Anand Balasubramaniam, Ivan Radovanovic, Gelareh Zadeh, Tim-Rasmus Kiehl, Abhijit Guha
Journal: Cancer Research (2009)

Schwannomas, although benign, can be fatal or give rise to significant morbidity due to an unpredictable growth rate. They can reoccur after surgery or radiation, current treatments each with significant inherent risks. These risks are further amplified in neurofibromatosis type 2 (NF2), a germ line predisposition syndrome characterized by multiple schwannomas, underlying the need for biological targeted therapies. Gleevec (STI571, imatinib mesylate), in addition to the bcr-abl oncogene in chronic myelogenous leukemia, inhibits c-kit and platelet-derived growth factor receptor (PDGFR) signaling, thereby expanding its use to several malignant and benign human diseases. In the present study, we show that human sporadic and NF2-associated schwannomas have increased expression along with activation of PDGFR-alpha, PDGFR-beta, and c-kit receptors, compared with normal or traumatic nerve. Using the human NF2-null HEI-193 schwannoma cell line, Gleevec inhibited schwannoma viability, proliferation, and anchorage-independent growth, as well as induced apoptosis in a dose-dependent manner (IC(50) 5-10 micromol/L). These antitumorigenic effects were correlated to inhibition of PDGFR-alpha, PDGFR-beta, and c-kit activation/phosphorylation and major downstream signaling pathways. Lack of robust xenograft or transgenic models of schwannomas prevents extension of these studies in vivo. However, the established long track record and tolerable toxicity of Gleevec already in clinical use and our preclinical data lead us to propose that Gleevec should be evaluated in human schwannomas with shown progressive growth.
Treasurer's Report for Financial Year (FY) 2012
Authors: A. McLysaght
Journal: Molecular Biology and Evolution (2013)

Society’s Total Assets as of May 31, 2013, are as follows: $1,625,201.14 


Cash accounts (Community Checking + Money Market Business): $1,441,288.02


Total CDs: $183,913.12






This report covers the period from June 1, 2012 to May 31, 2013. Due to the ongoing success of Molecular Biology and Evolution (MBE) and Genome Biology and Evolution (GBE), whose revenues continue to increase, the society remains in outstanding financial health. Society membership increased during FY 2012: membership-only subscriptions increased from 456 in 2011 to 732 in 2012, while society membership + journal subscriptions increased from 239 in 2011 to 313 in 2012.

The society used its income to publish its two journals, MBE and GBE, and to support its annual meeting, in 2012 held in Dublin, Ireland. This included providing increased graduate and postdoctoral travel awards, funding the Walter Fitch Prize Symposium (a cash prize for the winner and travel funds for all eight contestants), running the Undergraduate Diversity Mentoring Program (UDMP), supporting the travel and accommodation of Council members, and providing travel incentives for Associate Editors of MBE and GBE. We also supported three satellite meetings on important, focused and timely topics related to molecular evolutionary biology.


This year we received a donation of $2000USD from Masatoshi Nei to be used to set up a fund to support an honorarium for publication in MBE of the annual Nei Lecture given by the President of SMBE during the annual meeting. The 2013 Nei Lecture is to be the first lecture published under this scheme. The total value of the honorarium is to be $4000USD. 


	Expense Category	June 1, 2012 – May 31, 2013 USD
Interest income	748.81	
OUP journal revenue (MBE)	554,002.00	
OUP journal revenue (GBE)	74,982.00	
Society fees collected by OUP	22,288.00	
Annual meeting reimbursement	0.00	
Nei Lecture fund donation (Masatoshi Nei)	2,000.00	
Total inflows	654,020.81	
2013 annual meeting (partial)	25000.00	
SMBE satellite meetings	65069.50	
Support for diversity programs (e.g., UDMP, childcare subsidy)	17567.31	
Nei Lecture publication honorarium	0	
Bank charges	120.00	
Accounting	1,725.00	
Corporation fee	40.00	
Fitch Prize	1,500.00	
SMBE council and editors-in-chief travel	30,710.40	
MBE/GBE associate editors travel incentive	96775.62	
SMBE travel awards (Fitch, graduate, postdoc)	54719.25	
SMBE website maintenance	3,756.42	
SMBE treasurer expenses	0.00	
MBE editorial office expenses	111,519.42	
MBE editor expenses	103,500.00	
GBE editor expenses	25,000.00	
GBE “Highlight” honoraria	10,329.00	
Postage	453.11	
Total Outflows	547,785.03	
Overall Total	106,235.78	


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Impact of management guidelines on the outcome of severe community acquired pneumonia
Authors: N. A. Hirani, J. T. Macfarlane
Journal: Thorax (1997)

Ten years ago we published a study of 50 adults with severe community acquired pneumonia admitted to our intensive care unit and subsequently introduced guidelines for the management of severe community acquired pneumonia which are largely in accordance with those of the British Thoracic Society. The results of a follow up study are now reported in order to assess their impact on the outcome of this disease.Fifty seven cases of severe community acquired pneumonia admitted to our ICU between 1984 and 1993 were studied. Causal pathogens, clinical and laboratory features of severity, antibiotic therapy and mortality were studied and, where possible, compared with results from the previous study.Streptococcus pneumoniae, Legionella pneumophila and Staphylococcus aureus were the most frequent causes of severe community acquired pneumonia, as in the previous study. The intensity of microbial investigation has increased, particularly with regard to pneumococcal and Legionella antigen testing, the latter allowing earlier diagnosis of Legionella infection than previously. In spite of this, no pathogen was identified in 33% of cases compared with 18% previously. Indices of severity of illness were widely recognised, and a decrease in unplanned transfers to the ICU following "unexpected" cardiorespiratory arrest from 25% to 7% (p < 0.02) was found. Antibiotic therapy largely reflected guideline recommendations with 98% receiving a beta-lactam agent and 91% erythromycin. The overall mortality was 58% compared with 54% previously.Management guidelines for severe community acquired pneumonia have been widely adopted but without a reduction in mortality in our hospital. Factors other than early diagnosis, appropriate antibiotics, or prompt ICU transfer may influence the outcome in severe community acquired pneumonia.
Matching and melioration as accounts of reinforcement and drug addiction
Authors: Marc N. Branch
Journal: Behavioral and Brain Sciences (1996)

Abstract Heyman's view that addiction can be viewed as a natural outcome predictable by melioration and the matching law is provocative. Remaining to be explained more fully, however, are exactly how his view is an improvement on other reinforcement-based accounts. Included in these elaborations should be an account of how different “bookkeeping schemes” are developed and controlled and what new approaches to treatment and prevention of drug addiction are indicated.
Bundle-Branch Reentry and the Postpacing Interval After Entrainment by Right Ventricular Apex Stimulation
Authors: Jose L. Merino, Rafael Peinado, Ignacio Fernandez-Lozano, Maria Lopez-Gil, Fernando Arribas, Leonardo J. Ramirez, Ignacio J. Echeverria, Jose A. Sobrino
Journal: Circulation (2001)

Diagnosis of bundle-branch reentry ventricular tachycardia (BBR-VT) by the standard approach is challenging, and this may lead to nonrecognition of this tachycardia mechanism. Because the postpacing interval (PPI) after entrainment has been correlated with the distance from the pacing site to the reentrant circuit, BBR-VT entrainment by pacing from the right ventricular apex (RVA) should result in a PPI similar to the tachycardia cycle length (TCL). This factor may differentiate BBR-VT from other mechanisms of wide-QRS-complex tachycardia with AV dissociation, such as myocardial reentrant VT (MR-VT) or AV nodal reentrant tachycardia (AVNRT), in which the circuit is usually located away from the RVA.Transient entrainment by RVA pacing was attempted in 18 consecutive BBR-VTs and finally achieved in 13. Results were compared with those found in 59 consecutive MR-VTs and 50 consecutive AVNRTs. The mean PPI-TCL difference was significantly (P:<0.0001) shorter in the BBR-VT group (9+/-11 ms) than in the MR-VT (109+/-48 ms) and the AVNRT (150+/-29 ms) groups. No BBR-VT showed a PPI-TCL >30 ms (range -12 to 24 ms). Except for 2 MR-VTs, no MR-VT (range 21 to 211 ms) or AVNRT (range 100 to 215 ms) showed a PPI-TCL <30 ms.A PPI-TCL >30 ms, after entrainment by RVA stimulation, makes BBR-VT unlikely. Conversely, a PPI-TCL <30 ms is suggestive of BBR-VT but should lead to further investigation by use of conventional criteria.
PET Imaging in Head and Neck Cancer Patients to Monitor Treatment Response: A Future Role for EGFR-Targeted Imaging
Authors: Laura K. van Dijk, Otto C. Boerman, Johannes H.A.M. Kaanders, Johan Bussink
Journal: Clinical Cancer Research (2015)

Abstract Approximately 50,000 new cases of head and neck squamous cell carcinoma (HNSCC) are diagnosed worldwide each year and subsequently treated with surgery, chemotherapy, radiotherapy, and/or targeted therapy. The heterogeneity of the patient population in terms of treatment response drives the search for tumor-specific biomarkers. Imaging of biomarkers can reveal patient-specific responses to therapies and, if assessed early after the start of treatment, may allow adaptation of treatment regimens. In this review, tracers that have been tested to monitor treatment efficacy in HNSCC by PET scanning prior to and early after the onset of treatment are discussed. An important imaging target for this application in HNSCC patients is the EGFR. It steers the pathways related to proliferation, hypoxia, DNA damage repair, and apoptosis, all treatment-resistance mechanisms. The anti-EGFR antibody cetuximab has been labeled with various radionuclides and has been tested as an imaging biomarker in several HNSCC models. These studies suggest that EGFR-targeting tracers can be used to monitor EGFR receptor expression in HNSCC and have the potential to noninvasively monitor cetuximab treatment and steer individualized treatment regimens. Multiple factors can influence the uptake of EGFR-targeting tracers. Here, we discuss the relevance of gene and protein overexpression, mutations, and amplifications related to EGFR signaling. In addition, monoclonal antibody properties and the effect on the host immune system are reviewed in light of the future role of EGFR-targeted imaging in HNSCC. Clin Cancer Res; 21(16); 3602–9. ©2015 AACR.
Suppressor T cell clones from patients with acute Epstein-Barr virus-induced infectious mononucleosis.
Authors: F Wang, R M Blaese, K C Zoon, G Tosato
Journal: Journal of Clinical Investigation (1987)

Suppression and/or cytotoxicity are believed to play an important role in the defense against Epstein-Barr virus (EBV) infection. To analyze the role of suppressor T cells in relation to EBV, we sought to clone and study these T cells. Analysis of 152 T cell clones derived from the peripheral blood of two patients with acute EBV-induced infectious mononucleosis (IM) yielded 11 highly suppressive clones that had no cytotoxic activity for the natural killer sensitive K562 cell line, an autologous EBV-infected cell line, or an allogeneic EBV-infected B cell line. Four of six suppressor T cell clones also profoundly inhibited EBV-induced immunoglobulin production, and five of five clones delayed the outgrowth of immortalized cells. These results indicate that during acute IM, suppressor T cells capable of inhibiting B cell activation in the absence of cytotoxicity can be identified, and may play a key role in the control of EBV infection.
Identification of Functional Polymorphisms in the Promoter Region of the Human PICK1 Gene and Their Association With Methamphetamine Psychosis
Authors: Daisuke Matsuzawa, Kenji Hashimoto, Ryosuke Miyatake, Yukihiko Shirayama, Eiji Shimizu, Kazuhisa Maeda, Yoichi Suzuki, Yoichi Mashimo, Yoshimoto Sekine, Toshiya Inada, Norio Ozaki, Nakao Iwata, Mutsuo Harano, Tokutaro Komiyama, Mitsuhiko Yamada, Ichiro Sora, Hiroshi Ujike, Akira Hata, Akira Sawa, Masaomi Iyo
Journal: American Journal of Psychiatry (2007)

Protein interacting with C-kinase-1 (PICK1) plays a role in the targeting and clustering of dopamine transporter, which is the primary target site for the abused drug methamphetamine. Based on the interaction of PICK1 with dopamine transporter, it is of particular interest to investigate the association between the PICK1 gene and methamphetamine abusers.The authors studied the association between PICK1 gene polymorphisms and methamphetamine abusers in a Japanese group. Two hundred and eight methamphetamine abusers and 218 healthy comparison subjects were enrolled in the study. Furthermore, the authors also examined the effects of single nucleotide polymorphisms (SNPs) in the promoter and 5'-untranslated region on transcription levels of PICK1.The authors identified four highly frequent SNPs, rs737622 (-332 C/G) and rs3026682 (-205 G/A) in the promoter region and rs713729 (T/A) in intron3 and rs2076369 (T/G) in intron4. Of these SNPs, rs713729 was significantly associated with methamphetamine abusers in general, and rs713729 and rs2076369 were significantly associated with those with spontaneous relapse of psychosis. Furthermore, haplotype analysis revealed that specific haplotypes of these SNPs were associated with methamphetamine abusers. A gene reporter assay revealed that the two SNPs in the promoter region significantly altered transcriptional activity.Our findings suggest that the PICK1 gene may be implicated in the susceptibility to spontaneous relapse of methamphetamine psychosis and that, as an intracellular adapter protein, PICK1 may play a role in the pathophysiology of methamphetamine psychosis.
Novel Mutation in Desmoplakin Causes Arrhythmogenic Left Ventricular Cardiomyopathy
Authors: Mark Norman, Michael Simpson, Jens Mogensen, Anthony Shaw, Sîan Hughes, Petros Syrris, Srijita Sen-Chowdhry, Edward Rowland, Andrew Crosby, William J. McKenna
Journal: Circulation (2005)

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a familial heart muscle disease characterized by structural, electrical, and pathological abnormalities of the right ventricle (RV). Several disease loci have been identified. Mutations in desmoplakin have recently been isolated in both autosomal-dominant and autosomal-recessive forms of ARVC. Primary left ventricular (LV) variants of the disease are increasingly recognized. We report on a large family with autosomal-dominant left-sided ARVC.The proband presented with sudden cardiac death and fibrofatty replacement of the LV myocardium. The family was evaluated. Diagnosis was based on modified diagnostic criteria for ARVC. Seven had inferior and/or lateral T-wave inversion on ECG, LV dilatation, and ventricular arrhythmia, predominantly extrasystoles of LV origin. Three had sustained ventricular tachycardia; 7 had late potentials on signal-averaged ECG. Cardiovascular magnetic resonance imaging in 4 patients revealed wall-motion abnormalities of the RV and patchy, late gadolinium enhancement in the LV, suggestive of fibrosis. Linkage confirmed cosegregation to the desmoplakin intragenic marker D6S2975. A heterozygous, single adenine insertion (2034insA) in the desmoplakin gene was identified in affected individuals only. A frameshift introducing a premature stop codon with truncation of the rod and carboxy terminus of desmoplakin was confirmed by Western blot analysis.We have described a new dominant mutation in desmoplakin that causes left-sided ARVC, with arrhythmias of LV origin, lateral T-wave inversion, and late gadolinium enhancement in the LV on magnetic resonance images. Truncation of the carboxy terminus of desmoplakin and consequent disruption of intermediate filament binding may account for the predominant LV phenotype.
Myeloid Biomarkers Associated with Glioblastoma Response to Anti-VEGF Therapy with Aflibercept
Authors: John F. de Groot, Yuji Piao, Hai Tran, Mark Gilbert, Hua-Kang Wu, Jun Liu, B. Nebiyou Bekele, Tim Cloughesy, Minesh Mehta, H. Ian Robins, Andrew Lassman, Lisa DeAngelis, Kevin Camphausen, Alice Chen, WKA Yung, Michael Prados, Patrick Y. Wen, John V. Heymach
Journal: Clinical Cancer Research (2011)

VEGF and infiltrating myeloid cells are known regulators of tumor angiogenesis and vascular permeability in glioblastoma. We investigated potential blood-based markers associated with radiographic changes to aflibercept, which binds VEGF and placental growth factor (PlGF) in patients with recurrent glioblastoma.In this single-arm phase II trial, aflibercept was given intravenously every two weeks until disease progression. Plasma and peripheral blood mononuclear cells were collected at baseline and 24 hours, 14 days, and 28 days posttreatment. Plasma cytokines and angiogenic factors were quantified by using ELISA and multiplex bead assays, and myeloid cells were assessed by flow cytometry in a subset of patients.Circulating levels of VEGF significantly decreased 24 hours after treatment with aflibercept, coincident with radiographic response observed by MRI. PlGF initially decreased 24 hours posttreatment but increased significantly by days 14 and 28. Lower baseline levels of PlGF, elevated baseline levels of CTACK/CCL27, MCP3/CCL7, MIF, and IP-10/CXCL10, and a decrease in VEGFR1(+) monocytes from baseline to 24 hours were all associated with improved response. Tumor progression was associated with increases in circulating matrix metalloproteinase 9.These data suggest that decreases in VEGF posttreatment are associated with radiographic response to aflibercept. Elevated baseline chemokines of monocyte lineage in responding patients supports a role for myeloid cells and chemokines as potential biomarkers and regulators of glioma angiogenesis.
New Opportunities in Vasopressin and Oxytocin Research: A Perspective from the Amygdala
Authors: Ron Stoop, Chloé Hegoburu, Erwin van den Burg
Journal: Annual Review of Neuroscience (2015)

In the present review, we discuss how the evolution of oxytocin and vasopressin from a single ancestor peptide after gene duplication has stimulated the development of the vertebrate social brain. Separate production sites became possible with a hypothalamic development, which, interestingly, is triggered by the same transcription factors that underlie the development of various subcortical regions where vasopressin and oxytocin receptors are adjacently expressed and which are connected by inhibitory circuits. The opposite modulation of their output by vasopressin and oxytocin could thus create a dynamic equilibrium for rapid responsiveness to external stimuli. At the level of the individual, nurturing early in life can long-lastingly program oxytocin signaling, maintaining a capability of learning and sensitivity to external stimuli that contributes to development of social behavior in adulthood. Oxytocin and vasopressin are thus important for the development of a vertebrate brain that supports bonding between individuals and building of an interactive community.