tbuckley/cabot-search huggingface dataset:
Integration of Cistromic and Transcriptomic Analyses Identifies Nphs2, Mafb, and Magi2 as Wilms’ Tumor 1 Target Genes in Podocyte Differentiation and Maintenance
Authors: Lihua Dong, Stefan Pietsch, Zenglai Tan, Birgit Perner, Ralph Sierig, Dagmar Kruspe, Marco Groth, Ralph Witzgall, Hermann-Josef Gröne, Matthias Platzer, Christoph Englert
Journal: Journal of the American Society of Nephrology (2015)

The Wilms' tumor suppressor gene 1 (WT1) encodes a zinc finger transcription factor. Mutation of WT1 in humans leads to Wilms' tumor, a pediatric kidney tumor, or other kidney diseases, such as Denys–Drash and Frasier syndromes. We showed previously that inactivation of WT1 in podocytes of adult mice results in proteinuria, foot process effacement, and glomerulosclerosis. However, the WT1-dependent transcriptional network regulating podocyte development and maintenance in vivo remains unknown. Here, we performed chromatin immunoprecipitation followed by high-throughput sequencing with glomeruli from wild-type mice. Additionally, we performed a cDNA microarray screen on an inducible podocyte–specific WT1 knockout mouse model. By integration of cistromic and transcriptomic analyses, we identified the WT1 targetome in mature podocytes. To further analyze the function and targets of WT1 in podocyte maturation, we used an Nphs2-Cre model, in which WT1 is deleted during podocyte differentiation. These mice display anuria and kidney hemorrhage and die within 24 hours after birth. To address the evolutionary conservation of WT1 targets, we performed functional assays using zebrafish as a model and identified Nphs2, Mafb, and Magi2 as novel WT1 target genes required for podocyte development. Our data also show that both Mafb and Magi2 are required for normal development of the embryonic zebrafish kidney. Collectively, our work provides insights into the transcriptional networks controlled by WT1 and identifies novel WT1 target genes that mediate the function of WT1 in podocyte differentiation and maintenance.
Deficiency of UBR1, a ubiquitin ligase of the N-end rule pathway, causes pancreatic dysfunction, malformations and mental retardation (Johanson-Blizzard syndrome)
Authors: Martin Zenker, Julia Mayerle, Markus M Lerch, Andreas Tagariello, Klaus Zerres, Peter R Durie, Matthias Beier, Georg Hülskamp, Celina Guzman, Helga Rehder, Frits A Beemer, Ben Hamel, Philippe Vanlieferinghen, Ruth Gershoni-Baruch, Marta W Vieira, Miroslav Dumic, Ron Auslender, Vera L Gil-da-Silva-Lopes, Simone Steinlicht, Manfred Rauh, Stavit A Shalev, Christian Thiel, Andreas Winterpacht, Yong Tae Kwon, Alexander Varshavsky, André Reis
Journal: Nature Genetics (2005)
Noninvasive ventilation in acute cardiogenic pulmonary edema with haemodynamic instability
Authors: Inna Dolgova, Borys Todurov, Igor Kuzmich, Oleksii Stanishevskii, Irina Martyniuk
Journal: European Respiratory Journal (2012)

Background: Although noninvasive ventilation (NIV) in acute cardiogenic pulmonary edema (ACPE) is widely used, its use in patients with unstable hemodynamics is contradictory.  Aims: To evaluate NIV use in ACPE with low systolic blood pressure (SBP) and search for the correlates of it9s success.  Methods: Prospective interventional trial of all 22 patients with ACPE with SBP 75-90 mm Hg, with no acute arrhythmia, SaO2 90% on spontaneous breathing with 10 l per minute oxygen, cooperative, not hypercapneic, with low cardiac output due to acute myocardial infarction, mitral regurgitation or congestive heart failure, was done from July 1, 2010 through December 31, 2011. All patients were immediately started on conventional therapy (dobutamine and/or dopamine, morphine, furosemide, nitroglycerine) and NIV through a face mask with FiO2=1.0, initial PEEP 5 cm H2O and pressure support (PS) 5 cm H2O. Hemodynamic parameters, SaO2, central venous saturation (ScvO2), respiratory rate (RR) and tidal volume (Vt) were documented every 3 minutes. If no relief in 3 minutes, PEEP was enhanced to 7 cm H2O and after next 3 minutes PS added to 7 cm H2O.  Results: All patients had SaO2 90% and SBP≥90 mm Hg after 10 minutes. If at this moment RR was 30 and Vt 5 ml/kg of body weight, or more than low doses of cardiotonics were needed, the patient was intubated (4 patients).After 30 minutes, those who needed FiO2 60% on NIV, were oluguric and failed to rise ScvO2 above initial, were intubated (2 patients). No intubation was needed in 16 patients (73%). No factors correlated with NIV failure.  Conclusion: In selected hemodynamically unstable patients with ACPE NIV helps avoid intubation.
Profound spatial heterogeneity of coronary reserve. Discordance between patterns of resting and maximal myocardial blood flow.
Authors: R E Austin, G S Aldea, D L Coggins, A E Flynn, J I Hoffman
Journal: Circulation Research (1990)

We examined the ability of individual regions of the canine left ventricle to increase blood flow relative to baseline rates of perfusion. Regional coronary flow was measured by injecting radioactive microspheres over 90 seconds in seven anesthetized mongrel dogs. Preliminary experiments demonstrated a correlation between the regional distributions of blood flow during asphyxia and pharmacological vasodilatation with adenosine (mean r = 0.75; 192 regions in each of two dogs), both of which resulted in increased coronary flow. Subsequent experiments, during which coronary perfusion pressure was held constant at 80 mm Hg, examined the pattern of blood flow in 384 regions (mean weight, 106 mg) of the left ventricular free wall during resting flow and during maximal coronary flow effected by intracoronary adenosine infusion. We found that resting and maximal flow patterns were completely uncorrelated to each other in a given dog (mean r = 0.06, p = NS; n = 3 dogs). Furthermore, regional coronary reserve, defined as the ratio of maximal to resting flow, ranged from 1.75 (i.e., resting flow was 57% of maximum) to 21.9 (resting flow was 4.5% of maximum). Thus, coronary reserve is spatially heterogeneous and determined by two distinct perfusion patterns: the resting (control) pattern and the maximal perfusion pattern. Normal hearts, therefore, contain small regions that may be relatively more vulnerable to ischemia. This may explain the patchy nature of infarction with hypoxia and at reduced perfusion pressures as well as the difficulty of using global parameters to predict regional ischemia. Despite the wide dispersion of coronary reserve, we found, by autocorrelation analysis, that reserve in neighboring regions (even when separated by a distance of several tissue samples) was significantly correlated. This also applied to patterns of resting myocardial flow. Thus, both resting coronary blood flow and reserve appear to be locally continuous and may define functional zones of vascular control and vulnerability, respectively.
Left Ventricular Function in Mammals of Greatly Different Size
Authors: J. P. Holt, E. A. Rhode, S. A. Peoples, Helga Kines
Journal: Circulation Research (1962)

Studies of left ventricular volume and pressure have been carried out in the control state in four classes of intact anesthetized mammals (horses, cattle, swine, and dogs), body weights of which varied 54-fold. On the basis of these studies of both large and small hearts, extending over a wide range, a pattern of function for the left ventricle of all mammals has been described. Mathematical equations are given describing the interrelationships between left ventricular end-diastolic volume and end-systolic volume, stroke volume, cardiac output, stroke-work, heart rate, and total peripheral resistance.
Pulmonary embolectomy using normothermic venous inflow occlusion
Authors: D. B. Clarke
Journal: Thorax (1968)

Five patients are presented who underwent emergency pulmonary embolectomy with the use of venous inflow occlusion at normothermia. Two of these patients made satisfactory recoveries. It is suggested that this technique is of value in centres where facilities for providing cardiopulmonary bypass are not available.
Impact of Medical Qigong on quality of life, fatigue, mood and inflammation in cancer patients: a randomized controlled trial
Authors: B. Oh, P. Butow, B. Mullan, S. Clarke, P. Beale, N. Pavlakis, E. Kothe, L. Lam, D. Rosenthal
Journal: Annals of Oncology (2009)

BackgroundSubstantial numbers of cancer patients use complementary medicine therapies, even without a supportive evidence base. This study aimed to evaluate in a randomized controlled trial, the use of Medical Qigong (MQ) compared with usual care to improve the quality of life (QOL) of cancer patients.Patients and methodsOne hundred and sixty-two patients with a range of cancers were recruited. QOL and fatigue were measured by Functional Assessment of Cancer Therapy—General and Functional Assessment of Cancer Therapy—Fatigue, respectively, and mood status by Profile of Mood State. The inflammatory marker serum C-reactive protein (CRP) was monitored serially.ResultsRegression analysis indicated that the MQ group significantly improved overall QOL (t144 = -5.761, P < 0.001), fatigue (t153 = -5.621, P < 0.001), mood disturbance (t122 =2.346, P = 0.021) and inflammation (CRP) (t99 = 2.042, P < 0.044) compared with usual care after controlling for baseline variables.ConclusionsThis study indicates that MQ can improve cancer patients’ overall QOL and mood status and reduce specific side-effects of treatment. It may also produce physical benefits in the long term through reduced inflammation.
Heterogeneity of the BALB/c antiphosphorylcholine antibody response at the precursor cell level.
Authors: P J Gearhart, N H Sigal, N R Klinman
Journal: The Journal of Experimental Medicine (1975)

Immune responsiveness to phosphorylcholine (PC) in BALB/c mice has been characterized by combining (a) usuage of highly sensitive radioimmunoassays for quantitation of antibody, heavy-chain class, and idiotype on a weight basis; (b) isolation of PC-specific B cells in fragment cultures; and (c) stimulation in a carrier-primed environment with the PC hapten coupled to carrier through a tripeptide spacer in order to maximize carrier recognition. The specificity and accuracy of the radioimmunoassays have veen verified by specific inhibition, lack of nonspecific binding, and excellent concordance of values for monoclonal antibody concentration obtained independently for Fab and idiotype content. The latter evidence also serves as strong confirmation of the monoclonality of in vitro monofocal responses as well as the preservation of the idiotype on antibodies of differing immunoglobulin classes. The results indicate that while B cells expressing the TEPC 15 idiotype predominate, other idiotypes may be represented by 2-50% of PC-specific precursors, and monoclonal antibodies even of the TEPC 15 idiotype are produced in both the IgM and IgG1 immunoglobulin classes. These findings are confirmed by the analysis of serum antibodies produced in carrier-primed mice immunized with hapten coupled through a tripeptide spacer, thus re-emphasizint the enhancement of primary responsiveness, particularly IgG1 production, by maximizing carrier recognition. The finding of idiotype diversity in the PC response, as well as diversity of expression in terms of quantity and immunoglobulin class of antibody synthesized by the clonal progeny of B cells within the TEPC 15 clonotype, emphasize the heterogeneity of the B-cell population both in terms of specificity repertoire and the physiological state of cells even within a single clonotype.
INVESTIGATION AND TREATMENT OF ENDOCRINOLOGICAL DISORDERS
Authors: John Anderson, K.D. Bagshawe, D.A.K. Black, W.I. Cranston, P.B.S. Fowler, J.M. Ledingham, J. Lee, N. Morris, M.D. Milne, H.E. De Wardener, O.M. Wrong, A.L. Wyman
Journal: The Lancet (1972)
Cytotrophoblast induction of arterial apoptosis and lymphangiogenesis in an in vivo model of human placentation
Authors: K. Red-Horse
Journal: Journal of Clinical Investigation (2006)

We studied the vascular effects of invasive human cytotrophoblasts in vivo by transplanting placental villi to the fifth mammary fat pads or beneath the kidney capsules of Scid mice. Over 3 weeks, robust cytotrophoblast invasion was observed in both locations. The architecture of the mammary fat pad allowed for detailed analysis of the cells’ interactions with resident murine blood vessels, which revealed specific induction of apoptosis in the endothelial cells and smooth muscle walls of the arterioles. This finding, and confirmation of the results in an in vitro coculture model, suggests that a parallel process is important for enabling cytotrophoblast endovascular invasion during human pregnancy. Cytotrophoblast invasion of the kidney parenchyma was accompanied by a robust lymphangiogenic response, while in vitro, the cells stimulated lymphatic endothelial cell migration via the actions of VEGF family members, FGF, and TNF-α. Immunolocalization analyses revealed that human pregnancy is associated with lymphangiogenesis in the decidua since lymphatic vessels were not a prominent feature of the nonpregnant endometrium. Thus, the placenta triggers the development of a decidual lymphatic circulation, which we theorize plays an important role in maintaining fluid balance during pregnancy, with possible implications for maternal-fetal immune cell trafficking.
Regulation of T helper type 2 cell differentiation by murine Schnurri-2
Authors: Motoko Y. Kimura, Hiroyuki Hosokawa, Masakatsu Yamashita, Akihiro Hasegawa, Chiaki Iwamura, Hiroshi Watarai, Masaru Taniguchi, Tsuyoshi Takagi, Shunsuke Ishii, Toshinori Nakayama
Journal: The Journal of Experimental Medicine (2005)

Schnurri (Shn) is a large zinc finger protein implicated in cell growth, signal transduction, and lymphocyte development. Vertebrates possess at least three Shn orthologues (Shn-1, Shn-2, and Shn-3), which appear to act within the bone morphogenetic protein, transforming growth factor β, and activin signaling pathways. However, the physiological functions of the Shn proteins remain largely unknown. In Shn-2–deficient mice, mature peripheral T cells exhibited normal anti–T cell receptor–induced proliferation, although there was dramatic enhancement in the differentiation into T helper type (Th)2 cells and a marginal effect on Th1 cell differentiation. Shn-2–deficient developing Th2 cells showed constitutive activation of nuclear factor κB (NF-κB) and enhanced GATA3 induction. Shn-2 was able to compete with p50 NF-κB for binding to a consensus NF-κB motif and inhibit NF-κB–driven promoter activity. Thus, Shn-2 plays a crucial role in the control of Th2 cell differentiation by regulating NF-κB function.
Targeted Therapy for Non–Small Cell Lung Cancer
Authors: James R. Jett, Laurie L. Carr
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

The treatment of advanced non-small cell lung cancer has been with systemic chemotherapy and usually consists of a platinum doublet chemotherapy. The identification of somatic driver mutations has resulted in new drugs that target these mutations. This report discusses the two most important new targeted therapy drugs for the treatment of advanced non-small cell lung cancer that have these driver mutations.
Lupus erythematosus tumidus as a separate subtype of cutaneous lupus erythematosus: reply from authors
Authors: A. Kuhn, V. Ruland, G. Bonsmann
Journal: British Journal of Dermatology (2010)

Conflicts of interest: none declared. Madam, We thank Dr Mutasim for his valuable comments and are grateful for the opportunity to clarify certain aspects of our study investigating lupus erythematosus tumidus (LET) as a separate subtype of cutaneous lupus erythematosus (CLE).1 Dr Mutasim remarks that the study ‘did not add anything new to what is already known about tumid lupus’, that it did not ‘accomplish a resolution to the objectives stated by the authors’, and that the objective of the paper, to evaluate ‘whether LET can be distinguished as a separate entity in the classification system of the disease, … seems to be ill conceived’. He further notes that the ‘results could not have been otherwise as the authors have preselected patients whom they have identified as having LET prior to their entry into the study’. The of concern Dr Mutasim is comprehensible if our objective would have been to define LET as its own entity; however, this has already been shown by several groups.2 In our study, we sought to investigate if this existing entity of LET can be considered a separate subtype in the classification of CLE and be distinguished from other forms of CLE.1 Therefore, it was necessary to include patients with LET that had been diagnosed prior to inclusion in the study and to compare with other disease subtypes, such as subacute CLE (SCLE) and discoid lupus erythematosus (DLE) as the most common form of chronic CLE (CCLE).
Classical Clinical Trial Design in Testicular Cancer: Time to Move On
Authors: Craig R. Nichols, Bruce Roth, Christian Kollmannsberger
Journal: Journal of Clinical Oncology (2012)

Italian]. Minerva Ginecol 42:515-518, 1990 6. Jacoby VL, Autry A, Jacobson G, et al: Nationwide use of laparoscopic hysterectomy compared with abdominal and vaginal approaches. Obstet Gynecol 114:1041-1048, 2009 7. Seamon LG, Fowler JM, Richardson DL, et al: A detailed analysis of the learning curve: Robotic hysterectomy and pelvic-aortic lymphadenectomy for endometrial cancer. Gynecol Oncol 114:162-167, 2009 8. Leitao MM Jr, Gardner GJ, Briscoe G, et al: Comparison of robotically assisted and standard laparoscopic procedures in patients with endometrial cancer. Presented at the Society of Gynecologic Oncologists 42nd Annual Meeting on Women’s Cancer 2011, Orlando, FL, March 6-9, 2011 (abstr 296) 9. Jonsdottir GM, Jorgensen S, Cohen SL, et al: Increasing minimally invasive hysterectomy: Effect on cost and complications. Obstet Gynecol 117:1142-1149, 2011 10. Wikipedia: IBM 5100. http://en.wikipedia.org/wiki/IBM_5100 11. Apple: iPad. http://www.apple.com/ipad/
The link between enthesitis and arthritis in psoriatic arthritis: a switch to a vascular phenotype at insertions may play a role in arthritis development
Authors: Sibel Z Aydin, Zoe R Ash, Ilaria Tinazzi, Concepción Castillo-Gallego, Chung Kwok, Caroline Wilson, Mark Goodfield, Paolo Gisondi, Ai Lyn Tan, Helena Marzo-Ortega, Paul Emery, Richard J Wakefield, Dennis G McGonagle
Journal: Annals of the Rheumatic Diseases (2012)

Objective Subclinical enthesopathy is recognised in both psoriasis and psoriatic arthritis (PsA). This study used ultrasonography with power Doppler (PD) to test the hypothesis that subclinical enthesopathy in PsA was associated with an ‘inflammatory’ or vascular phenotype compared to that seen in psoriasis. Methods 100 patients with a mean age of 46.3 years (SD 15) (42 with psoriasis and 58 with PsA) and 23 matched healthy controls (HC) from two centres were included. 1230 lower limb entheses were scanned by ultrasonographers blinded to clinical details. Both inflammatory and chronic features of enthesopathy were scored. Results Psoriasis patients (with or without arthritis) were more likely to express a vascular phenotype, with higher inflammation-related enthesopathy scores than HC (for inflammation p&lt;0.0001, for chronicity p=0.02, for total ultrasound scores p&lt;0.0001). The PsA patients had higher ultrasound enthesopathy scores than psoriasis patients (inflammation p=0.04, chronicity p=0.02) and HC (inflammation p&lt;0.0001, chronicity p=0.003). When symptomatic entheses were excluded, PsA patients still had higher PD scores than psoriasis patients (p=0.003). Doppler positivity in at least one entheseal site was observed more frequently in PsA (21/58, 36.2%) versus psoriasis (4/42, 9.5%; p=0.002). Conclusions This study shows that the ultrasound appearances of subclinical enthesitis in psoriasis differ from the subclinical enthesitis in PsA, with PsA patients having more PD. This is suggestive of a more inflammatory or vascular process in PsA, and offers potentially novel insights into the progression from skin to joint disease in psoriasis.
Reasons to be physically active differ from reasons to be sedentary in COPD: A qualitative analysis
Authors: Jorine E. Hartman, Nick H.T. ten Hacken, H. Marike Boezen, Mathieu H.G. de Greef
Journal: European Respiratory Journal (2012)

The daily physical activity (DPA) level in COPD patients is low, notwithstanding its beneficial effects. For the development of successful prevention and management programs it would be helpful to gain insight in the reasons why COPD patients are physically active or sedentary. The aim of the study is to assess this in a qualitative way.  115 COPD patients (68% male, FEV 1 %pred 58±28, age 65±9 years) were interviewed in-depth. Furthermore, DPA (tri-axial accelerometer), lung function and dyspnea (MRC-scale) were determined. Answers were categorized according to the Grounded Theory. Afterwards descriptive analysis using k-means cluster analysis was performed.  The cluster analysis shows 2 clusters, one cluster with a high DPA level (n=52) and the second with a low DPA level (n=60) (figure1). A high DPA level was related to being physically active because of fun, because of having a continuous active lifestyle in the past, the number of reasons mentioned to be physically active and self-efficacy. A low DPA level was related to being sedentary because of bad weather influencing health, financial constraints, bad health and shame to be physically active.  This study shows that reasons to be physically active or sedentary are related to the level of daily physical activity in COPD patients. These factors could be useful for developing physical activity enhancement programs.
CLONAL NATURE OF THE IMMUNE RESPONSE TO PHOSPHORYLCHOLINE
Authors: J. Latham Claflin, Rose Lieberman, Joseph M. Davie
Journal: The Journal of Experimental Medicine (1974)

The relationship between receptor molecules on antigen-binding lymphocytes (ABC) and antibody produced by antibody-secreting cells was studied in inbred strains of mice using the immune response to phosphorylcholine (PC) as a model system. Splenic and lymph node lymphocytes of nonimmune mice possess rare lymphocytes which bind 125I-labeled PC-bovine serum albumin. The frequency of PC-ABC increases after immunization and is paralleled by a rise in the frequency of PC-specific antibody-producing cells. Both of these responses are thymus independent. The receptors on these ABC display specificity for PC and are exclusively of the IgM class. In one of the strains, BALB/c, the receptors possess the same idiotype and fine degree of specificity for PC and two of its analogues, glycerophosphorylcholine and choline, that are characteristic of a PC-binding myeloma, HOPC 8. Furthermore, the idiotype and class of the receptor in these mice do not change during the course of the immune response. These data provide more direct evidence for the immunelogic relevance of receptor-bearing lymphocytes.