tbuckley/cabot-search huggingface dataset:
Novel proteins associated with risk for coronary heart disease or stroke among postmenopausal women identified by in-depth plasma proteome profiling
Authors: Ross L Prentice, Sophie Paczesny, Aaron Aragaki, Lynn M Amon, Lin Chen, Sharon J Pitteri, Martin McIntosh, Pei Wang, Tina Buson Busald, Judith Hsia, Rebecca D Jackson, Jacques E Rossouw, JoAnn E Manson, Karen Johnson, Charles Eaton, Samir M Hanash
Journal: Genome Medicine (2010)

Abstract Background Coronary heart disease (CHD) and stroke were key outcomes in the Women's Health Initiative (WHI) randomized trials of postmenopausal estrogen and estrogen plus progestin therapy. We recently reported a large number of changes in blood protein concentrations in the first year following randomization in these trials using an in-depth quantitative proteomics approach. However, even though many affected proteins are in pathways relevant to the observed clinical effects, the relationships of these proteins to CHD and stroke risk among postmenopausal women remains substantially unknown. Methods The same in-depth proteomics platform was applied to plasma samples, obtained at enrollment in the WHI Observational Study, from 800 women who developed CHD and 800 women who developed stroke during cohort follow-up, and from 1-1 matched controls. A plasma pooling strategy, followed by extensive fractionation prior to mass spectrometry, was used to identify proteins related to disease incidence, and the overlap of these proteins with those affected by hormone therapy was examined. Replication studies, using enzyme-linked-immunosorbent assay (ELISA), were carried out in the WHI hormone therapy trial cohorts. Results Case versus control concentration differences were suggested for 37 proteins (nominal P &lt; 0.05) for CHD, with three proteins, beta-2 microglobulin (B2M), alpha-1-acid glycoprotein 1 (ORM1), and insulin-like growth factor binding protein acid labile subunit (IGFALS) having a false discovery rate &lt; 0.05. Corresponding numbers for stroke were 47 proteins with nominal P &lt; 0.05, three of which, apolipoprotein A-II precursor (APOA2), peptidyl-prolyl isomerase A (PPIA), and insulin-like growth factor binding protein 4 (IGFBP4), have a false discovery rate &lt; 0.05. Other proteins involved in insulin-like growth factor signaling were also highly ranked. The associations of B2M with CHD ( P &lt; 0.001) and IGFBP4 with stroke ( P = 0.005) were confirmed using ELISA in replication studies, and changes in these proteins following the initiation of hormone therapy use were shown to have potential to help explain hormone therapy effects on those diseases. Conclusions In-depth proteomic discovery analysis of prediagnostic plasma samples identified B2M and IGFBP4 as risk markers for CHD and stroke respectively, and provided a number of candidate markers of disease risk and candidate mediators of hormone therapy effects on CHD and stroke. Clinical Trials Registration ClinicalTrials.gov identifier: NCT00000611
Perturbation of the Tumor Necrosis Factor–Related Apoptosis-Inducing Ligand Cascade in Ovarian Cancer: Overexpression of FLIPL and Deregulation of the Functional Receptors DR4 and DR5
Authors: Peter Horak, Dietmar Pils, Alexandra Kaider, Alexander Pinter, Katarzyna Elandt, Cornelia Sax, Christoph C. Zielinski, Reinhard Horvat, Robert Zeillinger, Alexander Reinthaller, Michael Krainer
Journal: Clinical Cancer Research (2005)

Epithelial ovarian cancer is the most common cause of mortality from gynecologic malignancies. Due to advanced stage at diagnosis, most patients need systemic treatment in addition to surgery. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) is a member of the TNF family with a promising toxicity profile and synergistic activity with chemotherapeutic agents.We used an arrayed panel of epithelial ovarian cancer tissue to assess the protein expression of TRAIL and the clinically most relevant members of its pathway death receptors 4 and 5 (DR4 and DR5) and the long form of FLICE inhibitory protein (FLIPL).We could show that a majority (66.2%) of the tumor tissues displayed either reduced DR4/DR5 expression (20.6%), increased FLIPL expression (39.7%), or both (5.9%) as determined by immunohistochemistry. Furthermore, higher TRAIL expression in the surrounding connective tissue but not in the tumor cells is significantly (P<0.05) linked with favorable overall survival in advanced-stage patients.Mechanisms to escape the immune surveillance mediated by TRAIL are developed by ovarian cancer cells in a high percentage. TRAIL expression in the ovarian cancer microenvironment has an effect on overall survival. These findings enhance our understanding of ovarian cancer pathology and might be helpful in guiding TRAIL-based therapy in future.
The frequency, longitudinal course, clinical associations, and causes of emotional distress during primary treatment of cerebral glioma
Authors: Alasdair Grant Rooney, Shanne McNamara, Mairi MacKinnon, Mary Fraser, Roy Rampling, Alan Carson, Robin Grant
Journal: Neuro-Oncology (2013)

Relatively little is known about the frequency, longitudinal course, independent associations, and reported causes of emotional distress in adults with primary cerebral glioma. We aimed to describe these features in an observational study. This was a twin-center prospective cohort study. Eligible adults were those with a new histological diagnosis of glioma who were receiving active management. Distress was measured using the National Comprehensive Cancer Network Distress Thermometer and problem checklist. Subjects were sampled at 3 timepoints: T1 (shortly after starting chemo/radiotherapy), T2 (3 months later), and T3 (6 months later). T1 n = 154; T2 n = 103; T3 n = 83. Significant distress was present in 36.4 ± 7.6% at T1, 35.9 ± 9.3% at T2, and 33.7 ± 10.2% at T3. Longitudinally, subjects with high distress at T1 (median Distress Thermometer score = 8; interquartile range [IQR] 7–9) remained highly distressed on follow-up (T2 median = 8, IQR 6–8; T3 median = 7, IQR 5–8) (Friedman test P = .304). Younger age, functional impairment, and concurrent major depressive disorder were independently associated with high distress (logistic regression χ2 for model = 39.882, P < .001, R2 = 0.312). The most frequently reported causes of distress were worry, fatigue, sleep difficulties, and sadness. Emotional difficulties were among the most common causes of distress at all 3 timepoints. At each timepoint, one-third of patients reported significant emotional distress, which persisted during follow-up among those initially highly distressed. Young, functionally impaired, and depressed glioma patients may particularly benefit from increased support.
Follicular T-to-be
Authors: Amy Maxmen
Journal: The Journal of Experimental Medicine (2009)

Helper T (Th) cell identity may not be for life. According to a pair of studies from Zaretsky et al. ([page 991][1]) and King and Mohrs ([page 1001][2]), Th2 cells can turn into follicular T cells when duty calls.

![Figure][3] 

IL -4–expressing CD4+ cells (red) that accumulate in B cell
Effects of allergic rhinitis on self-management and quality of life in adult patients with asthma
Authors: Junko Yamanaka, Nanae Ikeda, Satoshi Ogino, Hiroshi Fijiwara, Chiko Okada, Seijiro Minamoto
Journal: European Respiratory Journal (2014)

Introduction: Bronchial asthma is frequently complicated by allergic rhinitis (AR), and there is a close association between the two conditions. This has been suggested to make it difficult to control asthmatic symptoms. This has important implications for the effective provision of support by caregivers, and so clarification of the effects of AR on the effects on the self-management behaviors and Quality of life(Qol) of asthmatic patients will significantly contribute to the goal for asthma care, which is improvement in Qol.  Objective: To investigate the Effects of AR on the self-management and Qol in asthmatic patients.  Methods: We conducted a questionnaire survey based on self-management behaviors and AHQ-33 in 424 ambulatory asthmatic patients at medical institutions in Osaka Prefecture. These patients were divided into two groups: AR and non-AR groups, and we performed statistical analysis.  Results: The AR group consisted of 180 patients (42.5%); 73.3% of the patients had nasal symptoms. The patients in this group showed significantly negative results for two items of self-management behaviors: enough sleep and avoidance of build-up of stress. Also, these patients demonstrated higher scores in all Qol subscales, with significantly impaired Qol for the items of emotion and economics. According to the items, the AR group had significantly higher scores for worsening due to mental factors, frustration, inability to concentrate, and heavy economic burden of treatments.  Conclusions: The presence of AR in asthmatic patients was expected to reduce their willingness to cope with stress and, together with nasal symptoms, cause emotional disturbance and the worsening of asthma symptoms.
Unconscious influences on decision making: Neuroimaging and neuroevolutionary perspectives
Authors: Samantha J. Brooks, Dan J. Stein
Journal: Behavioral and Brain Sciences (2014)

Abstract Newell and Shanks provide a useful critique on unconscious decision making. However, they do not consider an important set of functional brain imaging studies of unconscious processes. Here we review briefly the relevant brain imaging and psychobiological literature and its implications for understanding unconscious decision making.
Platelet secretion and hemostasis require syntaxin-binding protein STXBP5
Authors: Shaojing Ye, Yunjie Huang, Smita Joshi, Jinchao Zhang, Fanmuyi Yang, Guoying Zhang, Susan S. Smyth, Zhenyu Li, Yoshimi Takai, Sidney W. Whiteheart
Journal: Journal of Clinical Investigation (2014)

Genome-wide association studies (GWAS) have linked genes encoding several soluble NSF attachment protein receptor (SNARE) regulators to cardiovascular disease risk factors. Because these regulatory proteins may directly affect platelet secretion, we used SNARE-containing complexes to affinity purify potential regulators from human platelet extracts. Syntaxin-binding protein 5 (STXBP5; also known as tomosyn-1) was identified by mass spectrometry, and its expression in isolated platelets was confirmed by RT-PCR analysis. Coimmunoprecipitation studies showed that STXBP5 interacts with core secretion machinery complexes, such as syntaxin-11/SNAP23 heterodimers, and fractionation studies suggested that STXBP5 also interacts with the platelet cytoskeleton. Platelets from Stxbp5 KO mice had normal expression of other key secretory components; however, stimulation-dependent secretion from each of the 3 granule types was markedly defective. Secretion defects in STXBP5-deficient platelets were confirmed via lumi-aggregometry and FACS analysis for P-selectin and LAMP-1 exposure. Interestingly, STXBP5-deficient platelets had altered granule cargo levels, despite having normal morphology and granule numbers. Consistent with secretion and cargo deficiencies, Stxbp5 KO mice showed dramatic bleeding in the tail transection model and defective hemostasis in the FeCl3-induced carotid injury model. Transplantation experiments indicated that these defects were due to loss of STXBP5 in BM-derived cells. Our data demonstrate that STXBP5 is required for normal arterial hemostasis, due to its contributions to platelet granule cargo packaging and secretion.
How To Handle Positive Sentinel Nodes?
Authors: C. Schmidt
Journal: JNCI Journal of the National Cancer Institute (2010)

and the National Comprehensive Cancer Network — recommend ALND when the sentinel nodes are positive. Yet studies show that in roughly half of all newly diagnosed breast cancer patients who undergo ALND, only the sentinel nodes are positive, indicating that the procedure is unnecessary about 50% of the time. In September, researchers published a controversial prospective study suggesting that ALND doesn’t improve outcomes in some sentinel node – positive patients. Led by Armando Giuliano, M.D., from the John Wayne Cancer Institute in Santa Monica, Calif., the study found that after 6 years ’ follow-up, SNB alone and SNB followed by ALND produced similar survival outcomes, as well as comparable regional and local tumor control among node-positive women treated with lumpectomy and whole-breast irradiation. The American College of Surgeons Oncology Group (ACOSOG) sponsored the study, which appeared in the Annals of Surgery. In another study, Min Yi, M.D., and colleagues from the M. D. Anderson Cancer Center in Houston reviewed case histories from nearly 27,000 node-positive patients in the National Cancer Institute’s SEER (Surveillance, Epidemiology, and End Results) database. Published last October in Annals of Surgical Oncology , the study found that patients who undergo SNB and ALND combined have worse diseasespecifi c survival than those who have SNB alone. But that’s probably because patients subjected to both procedures also have more advanced disease, as indicated by larger
A tumor-suppressor function for Fas (CD95) revealed in T cell-deficient mice.
Authors: S L Peng, M E Robert, A C Hayday, J Craft
Journal: The Journal of Experimental Medicine (1996)

Fas (CD95) and its ligand are central regulatory molecules in hematopoietic cells. Previous studies have suggested a role for Fas in the regulation of tumor progression, but Fas has not yet been conclusively identified as a tumor suppressor. Fas-deficient individuals lack malignant tumors, perhaps because of regulation by T cells. To investigate such a possibility, mice deficient in both T cells and Fas were generated, and they were found to develop severe B cell dysregulation characterized by malignant, lethal B cell lymphoma. Lymphoma arose from a monoclonal B220+CD19-CD5-CD23- B cell secreting immunoglobulin M, kappa rheumatoid factor. In contrast, animals containing alpha beta T cells, gamma delta T cells, and/or functional Fas suppressed the development of lymphoma. These data indicate that Fas functions as a tumor suppressor, and identifies roles for both alpha beta T cells and gamma delta T cells in Fas-independent tumor regulation.
Psoriasis treatment: current and emerging directed therapies
Authors: L S Winterfield
Journal: Annals of the Rheumatic Diseases (2005)

Quality of life studies in patients with cutaneous psoriasis attest to its significant impact on day to day activities and personal social interactions. Up to 40% of patients with psoriasis may develop psoriatic arthritis, usually within 5-10 years after onset of the cutaneous disease, heightening quality of life issues. These data have prompted an increased awareness and interest in more aggressive management of psoriasis; coupled with a better understanding of immunopathogenesis, this has led to the development of new agents targeting specific cells and molecules involved in the development and maintenance of psoriatic plaques. Although non-biological therapies, including methotrexate and ciclosporin, show significant efficacy their side effect profiles have precluded their long term use for moderate to severe psoriasis. This review concentrates on new biological agents, focusing on the three agents approved for psoriasis within the past 18 months (alefacept, efalizumab, and etanercept). Phase II and III trial data on other agents in development (adalimumab and infliximab) are also presented. Surveys show many patients want to be treated more aggressively. It is hoped that the introduction of new agents that are more targeted and that hold the promise of fewer side effects will cause patients and their physicians to reconsider systemic treatment and, as a consequence, stimulate other patients to reconsider treatment for psoriasis. Close cooperation between dermatologists and rheumatologists, particularly in the area of psoriatic joint disease, will enhance these considerations.
SOCS1 gene transfer accelerates the transition to heart failure through the inhibition of the gp130/JAK/STAT pathway
Authors: Antonio Cittadini, Maria Gaia Monti, Guido Iaccarino, Maria Carmina Castiello, Alfonso Baldi, Eduardo Bossone, Salvatore Longobardi, Alberto Maria Marra, Valentina Petrillo, Lavinia Saldamarco, Matthew John During, Luigi Saccà, Gianluigi Condorelli
Journal: Cardiovascular Research (2012)

The suppressors of cytokine signalling (SOCS) are identified inhibitors of cytokine and growth factor signalling that act via the Janus kinase (JAK) signal transducers and activators of transcription (STAT) pathways. Aberrant JAK/STAT signalling promotes progression from hypertrophy to heart failure. Little information is available concerning the role of SOCS in the transition from hypertrophy to heart failure. To this aim, we investigated the effects of SOCS1 overexpression obtained by in vivo adeno-associated gene transfer using an aortopulmonary cross-clamping technique in a chronic pressure-overload cardiac rat model. Rats were randomized into four groups: sham-operated (n = 18), aortic banding (AB) (n = 18), AB + viral vector encoding for haemoagglutinin (AB + HA, n = 16), and AB + viral vector encoding for SOCS1 (AB + SOCS1, n = 18). Echocardiographic and haemodynamic measurements were performed 15 weeks after banding. While SOCS3 was upregulated during the hypertrophic phase, SOCS1 transcript levels increased significantly between 15 and 20 weeks. Remodelling was markedly worse in AB + SOCS1, showed larger left ventricular internal dimensions (+16%), higher end-diastolic pressures (+57%) and wall stress (+45%), and reduced fractional shortening (−32%) compared with AB + HA; apoptotic rate was increased three­fold and the gp130 pathway was inhibited. Ex vivo experiments showed that mechanical stretch upregulated SOCS1 expression, which was in turn attenuated by tumour necrosis factor-α (TNF-α) inhibition. Enhanced SOCS1 myocardial signalling is associated with accelerated transition from hypertrophy to failure in an established model of pressure overload. SOCS1 may represent an attractive target for the prevention of heart failure progression.
Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett's oesophagus with high-grade dysplasia or early cancer: a multicentre randomised trial
Authors: F. G. I. van Vilsteren, R. E. Pouw, S. Seewald, L. Alvarez Herrero, C. M. T. Sondermeijer, M. Visser, F. J. W. ten Kate, K. C. Yu Kim Teng, N. Soehendra, T. Rosch, B. L. A. M. Weusten, J. J. G. H. M. Bergman
Journal: Gut (2011)

<h3>Objective</h3> After focal endoscopic resection (ER) of high-grade dysplasia (HGD) or early cancer (EC) in Barrett9s oesophagus (BO), eradication of all remaining BO reduces the recurrence risk. The aim of this study was to compare the safety of stepwise radical ER (SRER) versus focal ER followed by radiofrequency ablation (RFA) for complete eradication of BO containing HGD/EC. <h3>Methods</h3> A multicentre randomised clinical trial was carried out in three tertiary centres. Patients with BO ≤5 cm containing HGD/EC were randomised to SRER or ER/RFA. Patients in the SRER group underwent piecemeal ER of 50% of BO followed by serial ER. Patients in the ER/RFA group underwent focal ER for visible lesions followed by serial RFA. Follow-up endoscopy with biopsies (four-quadrant/2 cm BO) was performed at 6 and 12 months and then annually. The main outcome measures were: stenosis rate; complications; complete histological response for neoplasia (CR-neoplasia); and complete histological response for intestinal metaplasia (CR-IM). <h3>Results</h3> CR-neoplasia was achieved in 25/25 (100%) SRER and in 21/22 (96%) ER/RFA patients. CR-IM was achieved in 23 (92%) SRER and 21 (96%) ER/RFA patients. The stenosis rate was significantly higher in SRER (88%) versus ER/RFA (14%; p&lt;0.001), resulting in more therapeutic sessions in SRER (6 vs 3; p&lt;0.001) due to dilations. After median 24 months follow-up, one SRER patient had recurrence of EC, requiring ER. <h3>Conclusions</h3> In patients with BO ≤5 cm containing HGD/EC, SRER and ER/RFA achieved comparably high rates of CR-IM and CR-neoplasia. However, SRER was associated with a higher number of complications and therapeutic sessions. For these patients, a combined endoscopic approach of focal ER followed by RFA may thus be preferred over SRER. <h3>Clinical trial number</h3> NTR1337.
Novel glomerular lipoprotein deposits associated with apolipoprotein E2 homozygosity
Authors: Minoru Sakatsume, Moritoshi Kadomura, Iku Sakata, Naofumi Imai, Daisuke Kondo, Yutaka Osawa, Hisaki Shimada, Mitsuhiro Ueno, Takashi Miida, Shinichi Nishi, Masaaki Arakawa, Fumitake Gejyo
Journal: Kidney International (2001)
PHYLOGENETICALLY ASSOCIATED RESIDUES WITHIN THE VHIII SUBGROUP OF SEVERAL MAMMALIAN SPECIES
Authors: J. Donald Capra, Richard L. Wasserman, J. Michael Kehoe
Journal: The Journal of Experimental Medicine (1973)

Immunoglobulin heavy chains from IgG pools of several mammalian species have been subjected to Edman degradation on an automated protein sequencer. The percentage of unblocked vs. blocked heavy chains was estimated from the yield of the invariant valine in the second position. Further analysis of these unblocked polypeptides unequivocally placed them in the V(HIII) subgroup on the basis of homology with known human heavy chain sequences. The mammals studied could be divided into three distinct categories on the basis of the distribution of the V(HIII) subgroup. In several species the V(HIII) subgroup could not be detected while, in others, virtually all of the heavy chains belonged to this subgroup. Several species had intermediate amounts with the level of the V(HIII) subgroup restricted to between 19 and 29% of the total pool. Within experimental error, all members of a given order had a similar V(HIII) subgroup distribution. Further amino acid sequence studies illustrated a high degree of structural homogeneity in the heavy chains of IgG isolated from pooled sera of a number of mammalian species. The very close amino acid sequence homologies of the amino terminal 24 residues of the various pools corroborated conclusions previously obtained using several myeloma proteins from some of these same species. In particular, certain phylogenetically associated residues were identifiable at characteristic positions in the pools in confirmation of their identification in the myeloma proteins. The simplest assumptions would suggest that these findings are more compatible with a pauci-gene than a multi-gene basis for the generation of antibody diversity.