tbuckley/cabot-search huggingface dataset:
Raf-1 protein is required for growth factor-induced proliferation of hematopoietic cells.
Authors: K W Muszynski, F W Ruscetti, G Heidecker, U Rapp, J Troppmair, J M Gooya, J R Keller
Journal: The Journal of Experimental Medicine (1995)

Raf-1 is a 74-kD serine/threonine kinase located in the cell cytoplasm that is activated by phosphorylation in cells stimulated with a variety of mitogens and growth factors, including hematopoietic growth factors. Using c-raf antisense oligonucleotides to block Raf-1 expression, we have established that Raf-1 is required for hematopoietic growth factor-induced proliferation of murine cell lines stimulated by growth factors whose receptors are members of several different structural classes: (a) the hematopoietin receptor family, including interleukin (IL)-2, IL-3, IL-4, granulocyte colony-stimulating factor, granulocyte/macrophage colony-stimulating factor (GM-CSF), and erythropoietin; (b) the tyrosine kinase receptor class, including Steel factor and CSF-1; and (c) IL-6, leukemia inhibitory factor, and oncostatin M, whose receptors include the gp130 receptor subunit. Although results of previous experiments had suggested that IL-4 does not phosphorylate or activate the Raf-1 kinase, c-raf antisense oligonucleotides inhibited IL-4-induced proliferation of both myeloid and T cell lines, and IL-4 activated Raf-1 kinase activity in an IL-4-dependent myeloid cell line. In colony assays, c-raf antisense oligonucleotides completely inhibited colony formation of unseparated normal murine bone marrow cells stimulated with either IL-3 or CSF-1 and partially inhibited cells stimulated with GM-CSF. In addition, c-raf antisense oligonucleotides completely inhibited both IL-3- and GM-CSF-induced colony formation of CD34+ purified human progenitors stimulated with these same growth factors. Thus, Raf-1 is required for growth factor-induced proliferation of leukemic murine progenitor cell lines and normal murine and human bone marrow-derived progenitor cells regardless of the growth factor used to stimulate cell growth.
Are Nomograms Better Than Currently Available Stage Groupings for Bladder Cancer?
Authors: Cora N. Sternberg
Journal: Journal of Clinical Oncology (2006)

Bladder cancer is a highly aggressive neoplasm.It is the fourth most frequent solid tumor among men and the seventh most frequent solid tumor among women, with more than 350,000 new cases diagnosed annually worldwide. 1 Radical cystectomy with orthotopic bladder substitution is the preferred treatment for invasive transitional cell carcinoma.With the advent of orthotopic bladder substitution after cystectomy, the majority of fit patients are no longer burdened with external ileal conduits or cutaneous ureterostomies.Progress in operating techniques and postoperative care has also contributed to improvements in survival.However, after cystectomy, 5-year survival in major series ranges from 35% to 50%, but may also be as high as 65% when a high proportion of good prognosis pT2 patients are included. [2]3][4][5] High-risk patients with pT3-pT4 and/or pNϩ, M0 bladder cancer have a worse prognosis, and 5-year survival ranges between 25% to 35%.Histologic grade and TNM staging have been the most universally used methodologies to predict the risk of recurrence after cystectomy.The article by Bochner et al 6 in this issue of the Journal of Clinical Oncology reports a postoperative nomogram based on information from 9,064 patients after radical cystectomy for both superficial and invasive bladder cancer.The authors have constructed a database from some of the best international centers of excellence, and their nomogram represents the results of a long endeavor to collect and verify data from 12 collaborating institutions.Their aim was to develop a nomogram to predict the risk of recurrence at 5 years after cystectomy in patients with bladder cancer.The ultimate goal of such a tool is to aid clinicians in predicting the probability of progression after radical cystectomy and to identifying patients at high risk who may benefit from adjuvant chemotherapy after cystectomy.Although the authors make no therapeutic recommendations, this type of nomogram is potentially of tremendous importance because it has been extremely difficult to accrue patients to adequately sized randomized adjuvant chemotherapy trials.Models for determining the risk of recurrence and the need for adjuvant chemotherapy in colorectal and breast cancer are extremely useful, user friendly, and readily available online. 7 More recently, prognostic models and nomograms have been developed to determine patients at high risk with renal cell carcinoma 8-10 and prostate cancer. [11][][13] The authors have sought to develop a similar nomogram to the one that has become increasingly used in the management of patients with prostate cancer. 11 The current nomogram uses a
Physiological and morphological determinants of maximal expiratory flow in chronic obstructive lung disease
Authors: HA Tiddens, JM Bogaard, JC de Jongste, WC Hop, HO Coxson, PD Pare
Journal: European Respiratory Journal (1996)

Maximal expiratory flow in chronic obstructive pulmonary disease (COPD) could be reduced by three different mechanisms; loss of lung elastic recoil, decreased airway conductance upstream of flow-limiting segments; and increased collapsibility of airways. We hypothesized that decreased upstream conductance would be related to inflammation and thickening of the airway walls, increased collapsibility would be related to decreased airway cartilage volume, and decreased collapsibility to inflammation and thickening of the airway walls. Lung tissue was obtained from 72 patients with different degrees of COPD, who were operated upon for a solitary peripheral lung lesion. Maximal flow-static recoil (MFSR) plots to estimate upstream resistance and airway collapsibility were derived in 59 patients from preoperatively measured maximal expiratory flow-volume and pressure-volume curves. In 341 transversely cut airway sections, airway size, airway wall dimensions and inflammatory changes were measured. Airflow obstruction correlated with lung elastic recoil and the MFSR estimate of airway conductance but not to airway collapsibility or to the amount of airway cartilage. The upstream conductance decreased as the inner wall became thicker. Airway collapsibility did not correlate with the amount of airway cartilage, inflammation, or airway wall thickness. We conclude that the maximal flow-static recoil model does not adequately reflect the collapsibility of the flow-limiting segment.
High Loading of Polygenic Risk for ADHD in Children With Comorbid Aggression
Authors: Marian L. Hamshere, Kate Langley, Joanna Martin, Sharifah Shameem Agha, Evangelia Stergiakouli, Richard J.L. Anney, Jan Buitelaar, Stephen V. Faraone, Klaus-Peter Lesch, Benjamin M. Neale, Barbara Franke, Edmund Sonuga-Barke, Philip Asherson, Andrew Merwood, Jonna Kuntsi, Sarah E. Medland, Stephan Ripke, Hans-Christoph Steinhausen, Christine Freitag, Andreas Reif, Tobias J. Renner, Marcel Romanos, Jasmin Romanos, Andreas Warnke, Jobst Meyer, Haukur Palmason, Alejandro Arias Vasquez, Nanda Lambregts-Rommelse, Herbert Roeyers, Joseph Biederman, Alysa E. Doyle, Hakon Hakonarson, Aribert Rothenberger, Tobias Banaschewski, Robert D. Oades, James J. McGough, Lindsey Kent, Nigel Williams, Michael J. Owen, Peter Holmans, Michael C. O’Donovan, Anita Thapar
Journal: American Journal of Psychiatry (2013)

OBJECTIVE Although attention deficit hyperactivity disorder (ADHD) is highly heritable, genome-wide association studies (GWAS) have not yet identified any common genetic variants that contribute to risk. There is evidence that aggression or conduct disorder in children with ADHD indexes higher genetic loading and clinical severity. The authors examine whether common genetic variants considered en masse as polygenic scores for ADHD are especially enriched in children with comorbid conduct disorder. METHOD Polygenic scores derived from an ADHD GWAS meta-analysis were calculated in an independent ADHD sample (452 case subjects, 5,081 comparison subjects). Multivariate logistic regression analyses were employed to compare polygenic scores in the ADHD and comparison groups and test for higher scores in ADHD case subjects with comorbid conduct disorder relative to comparison subjects and relative to those without comorbid conduct disorder. Association with symptom scores was tested using linear regression. RESULTS Polygenic risk for ADHD, derived from the meta-analysis, was higher in the independent ADHD group than in the comparison group. Polygenic score was significantly higher in ADHD case subjects with conduct disorder relative to ADHD case subjects without conduct disorder. ADHD polygenic score showed significant association with comorbid conduct disorder symptoms. This relationship was explained by the aggression items. CONCLUSIONS Common genetic variation is relevant to ADHD, especially in individuals with comorbid aggression. The findings suggest that the previously published ADHD GWAS meta-analysis contains weak but true associations with common variants, support for which falls below genome-wide significance levels. The findings also highlight the fact that aggression in ADHD indexes genetic as well as clinical severity.
Contractile smooth muscle cells derived from hair-follicle stem cells
Authors: Jin Yu Liu, Hao Fan Peng, Stelios T. Andreadis
Journal: Cardiovascular Research (2008)

We hypothesized that hair-follicle stem cells can differentiate toward smooth contractile muscle cells, providing an autologous cell source for cardiovascular tissue regeneration.Smooth muscle progenitor cells (SMPCs) were obtained from ovine hair follicles using a tissue-specific promoter and fluorescence-activated cell sorting. Hair-follicle smooth muscle progenitor cells (HF-SMPCs) expressed several markers of vascular smooth muscle including alpha-actin, calponin, myosin heavy chain (MHC), caldesmon, smoothelin, and SM22. HF-SMPCs were highly proliferative and showed high clonogenic potential without any signs of chromosomal abnormalities as evidenced by karyotype analysis. HF-SMPCs compacted fibrin hydrogels to a similar extent as vascular smooth muscle cells from ovine umbilical veins (V-SMCs), indicating the development of the force-generating machinery. In addition, cylindrical tissue equivalents prepared with HF-SMPCs displayed significant contractility in response to vasoactive agonists including KCl and the thromboxane A2 mimetic U46619, suggesting that these cells had developed receptor and non-receptor-mediated pathways of contractility. Finally, transforming growth factor-beta1 promoted differentiation of HF-SMPCs toward a mature SMC phenotype as suggested by increased expression of MHC and enhanced matrix compaction.Our results suggest that hair follicles may be an easily accessible, autologous, and rich source of functional SMPC for cardiovascular tissue engineering and regenerative medicine.
IMMUNE RESPONSES IN VITRO
Authors: Robert E. Click, Loretta Benck, Barbara J. Alter, Judith C. Lovchik
Journal: The Journal of Experimental Medicine (1972)

The finding that the relationship of the in vitro and in vivo responses of different strains of mice is under genetic control indicates that at least two mechanisms must operate under in vivo conditions to control 19S antibody synthesis. One is involved in the termination of 19S antibody synthesis; the other has a regulatory role on the magnitude of the response. In light of these findings, various concepts based on other genetically controlled immune responses and on the limiting dilution technique should be reassessed. Furthermore, the suppressive in vivo mechanism may be an important type of control in the resistance or susceptibility to the establishment or maintainance of neoplasms.
How Many Different Roads May a Cell Walk down in Order to Become a Fibroblast?
Authors: Frank Strutz
Journal: Journal of the American Society of Nephrology (2008)

Renal interstitial fibroblasts are an essential component of the kidney interstitium and presumably the main effector of renal fibrogenesis, a process responsible for pernicious interstitial deposition of matrix and eventual loss of organ function. The origin of these matrix-producing cells has been
Surgical Ventricular Restoration Improves Mechanical Intraventricular Dyssynchrony in Ischemic Cardiomyopathy
Authors: Marisa Di Donato, Anna Toso, Vincent Dor, Michel Sabatier, Giuseppe Barletta, Lorenzo Menicanti, Fabio Fantini
Journal: Circulation (2004)

In ischemic cardiomyopathy, dyssynchrony of left ventricular (LV) mechanical contraction produces adverse hemodynamic consequences. This study tests the capacity of geometric rebuilding by surgical ventricular restoration (SVR) to restore a more synchronous contractile pattern after a mechanical, rather than electrical, intervention.A prospective study of the global and regional components of dyssynchrony was conducted in 30 patients (58+/-8 years of age) undergoing SVR at the Cardiothoracic Center of Monaco. The protocol used simultaneous measurements of ventricular volumes and pressure to construct pressure/volume (P/V) and pressure/length (P/L) loops. Angiograms were done before and after SVR to study a 600-ms cycle during atrial pacing at 100 bpm. Mean QRS duration was similar, at 100+/-17 ms preoperatively and 114+/-28 ms postoperatively (NS). Preoperative LV contraction was highly asynchronous, because P/V loops showed abnormal isometric phases with a right shifting. Endocardial time motion was either early or delayed at the end-systolic phase so that P/L loops were markedly abnormal in size, shape, and orientation. Postoperatively, SVR resulted in leftward shifting of P/V loops and increased area; endocardial time motion and P/L loops almost normalized to allow a better contribution of single regions to global ejection. The hemodynamic consequences of SVR were improved ejection fraction (30+/-13% to 45+/-12%; P=0.001); reduced end-diastolic and end-systolic volume index (202+/-76 to 122+/-48 and 144+/-69 to 69+/-40 mL/m(2); P=0.001); more rapid peak filling rate (1.75+/-0.7 to 2.32+/-0.7 EDV/s; P=0.0001); peak ejection rate (1.7+/-0.7 to 2.6+/-0.9 Sv/s; P=0.0002), and mechanical efficiency (0.56+/-0.15 to 0.65+/-0.18; P=0.04).SVR produces a mechanical intraventricular resynchronization that improves LV performance.
Transplanted Long-Term Cultured Pre-Bi Cells Expressing Calpastatin Are Resistant to B Cell Receptor–Induced Apoptosis
Authors: Antonio Ruiz-Vela, Fernando Serrano, Manuel A. González, José Luis Abad, Antonio Bernad, Masatoshi Maki, Carlos Martínez-A
Journal: The Journal of Experimental Medicine (2001)

Long-term cultured pre-B cells are able to differentiate into immunoglobulin (Ig)M-positive B cells (IgM+ cells) when transplanted into severe combined immunodeficient (SCID) mice. Based on previous studies, here we report the development of a reconstitution assay in nonobese diabetic/SCID (NOD/SCID) mice using pre-B cells, which allows us to study the role of calpains (calcium-activated endopeptidases) during B cell development as well as in B cell clonal deletion. Using this model, we show that calpastatin (the natural inhibitor of calpains) inhibits B cell receptor–induced apoptosis in IgM+ cells derived from transplanted mice. We thus hypothesize an important function for calpain in sculpting the B cell repertoire.
<i>NKX3.1</i> Haploinsufficiency Is Prognostic for Prostate Cancer Relapse following Surgery or Image-Guided Radiotherapy
Authors: Jennifer A. Locke, Gaetano Zafarana, Adrian S. Ishkanian, Michael Milosevic, John Thoms, Cherry L. Have, Chad A. Malloff, Wan L. Lam, Jeremy A. Squire, Melania Pintilie, Jenna Sykes, Varune Rohan Ramnarine, Alice Meng, Omer Ahmed, Igor Jurisica, Theo van der Kwast, Robert G. Bristow
Journal: Clinical Cancer Research (2011)

Despite the use of prostate specific antigen (PSA), Gleason-score, and T-category as prognostic factors, up to 40% of patients with intermediate-risk prostate cancer will fail radical prostatectomy or precision image-guided radiotherapy (IGRT). Additional genetic prognosticators are needed to triage these patients toward intensified combination therapy with novel targeted therapeutics. We tested the role of the NKX3.1 gene as a determinant of treatment outcome given its reported roles in tumor initiating cell (TIC) renewal, the DNA damage response, and cooperation with c-MYC during prostate cancer progression.Using high-resolution array comparative genomic hybridization (aCGH), we profiled the copy number alterations in TIC genes using tumor DNA from frozen needle biopsies derived from 126 intermediate-risk patients who underwent IGRT. These data were correlated to biochemical relapse-free rate (bRFR) by the Kaplan-Meier method and Cox proportional hazards models.A screen of the aCGH-IGRT data for TIC genes showed frequent copy number alterations for NKX3.1, PSCA, and c-MYC. NKX3.1 haploinsufficiency was associated with increased genomic instability independent of PSA, T-category, and Gleason-score. After adjusting for clinical factors in a multivariate model, NKX3.1 haploinsufficiency was associated with bRFR when tested alone (HR = 3.05, 95% CI: 1.46-6.39, P = 0.0030) or when combined with c-MYC gain (HR = 3.88, 95% CI: 1.78-8.49, P = 0.00067). A similar association was observed for patients following radical prostatectomy with a public aCGH database. NKX3.1 status was associated with positive biopsies post-IGRT and increased clonogen radioresistance in vitro.Our results support the use of genomic predictors, such as NKX3.1 status, in needle biopsies for personalized approaches to prostate cancer management.
Domiciliary nocturnal intermittent positive pressure ventilation in patients with respiratory failure due to severe COPD: long term follow up and effect on survival
Authors: S E Jones, S Packham, M Hebden, A P Smith
Journal: Thorax (1998)

There is increasing interest in the use of non-invasive nocturnal intermittent positive pressure ventilation (NIPPV) in the management of patients with chronic hypercapnoeic (type II) respiratory failure. Although this treatment enables patients requiring mechanical ventilatory support to the treated more readily at home, few studies have been done to demonstrate its long term benefits in chronic obstructive pulmonary disease (COPD) and the application of NIPPV in these circumstances remains controversial.Eleven patients in severe stable chronic type II respiratory failure due to COPD who were unresponsive to conventional treatments experienced symptomatic hypercapnia when receiving sufficient supplementary oxygen to result in an arterial oxygen saturation (SaO2) of > 90%. They were assessed for treatment with NIPPV, and its effects were observed for over two years using arterial blood gas tensions, spirometric parameters and body mass index (BMI), survival, hospital admissions, use of general practitioner resources, and patient satisfaction.Hospital admissions and GP consultations were halved after one year compared with the year before NIPPV and there was a sustained improvement in arterial blood gas tensions at 12 and 24 months when breathing air, despite progressive deterioration in ventilatory function. BMI did not change during the period of observation. The median survival was 920 days, with no patient dying within the first 500 days.Domiciliary NIPPV results in improvements in arterial blood gas tensions which are sustained after two years of treatment and reduces both hospital admissions and general practitioner visits by patients with severe COPD in hypercapnoeic respiratory failure. It is well tolerated and, although there was no control group, survival appears to be prolonged when these results are compared with those of the NOTT and MRC (LTOT) trials.
Cardiac and thromboembolic complications and mortality in patients undergoing total hip and total knee arthroplasty
Authors: J. A. Singh, M. R. Jensen, W. S. Harmsen, S. E. Gabriel, D. G. Lewallen
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Objective</h3> To study 90-day complications following total hip arthroplasty (THA) or total knee arthroplasty (TKA). <h3>Method</h3> In a population-based cohort of all Olmsted County residents who underwent a THA or TKA (1994-2008), we assessed 90-day occurrence and predictors of cardiac complications (myocardial infarction, cardiac arrhythmia or congestive heart failure), thromboembolic complications (deep venous thrombosis or pulmonary embolism) and mortality. <h3>Results</h3> 90-day complication rates after THA and TKA were: cardiac, 6.9% and 6.7%; thromboembolic, 4.0% and 4.9%; and mortality, 0.7% and 0.4%, respectively. In multivariable-adjusted logistic regression analyses, ASA class III–IV (OR 6.1, 95% CI:1.6-22.8) and higher Deyo–Charlson comorbidity score (OR 1.2, 95% CI:1.0-1.4) were significantly associated with odds of 90-day cardiac event post-THA in patients with no known previous cardiac event. In those with known previous cardiac disease, ASA class III–IV (OR 4.4, 95% CI:2.0-9.9), male gender (OR 0.5, 95% CI:0.3-0.9) and history of thromboembolic disease (OR 3.2; 95% CI:1.4-7.0) were significantly associated with odds of cardiac complication 90 days post-THA. No significant predictors of thromboembolism were found in THA patients. In TKA patients with no previous cardiac history, age &gt;65 years (OR 4.1, 95% CI:1.2-14.0) and in TKA patients with known cardiac disease, ASA class III–IV (OR 3.2, 95% CI:1.8-5.7) was significantly associated with odds of 90-day cardiac events. In TKA patients with no previous thromboembolic disease, male gender (OR 0.5, 95% CI:0.2-0.9) and higher Charlson index (OR 1.2, 95% CI:1.1-1.3) and in patients with known thromboembolic disease, higher Charlson index score (OR 1.2, 95% CI:1.1-1.4) was associated with odds of 90-day thromboembolic events. <h3>Conclusion</h3> Older age, higher comorbidity, higher ASA class and previous history of cardiac/thromboembolic disease were associated with an increased risk.
Prior Exposure to Medical and Dental X-rays Related to Tumors of the Parotid Gland1
Authors: S. Preston-Martin, D. C. Thomas, S. C. White, D. Cohen
Journal: JNCI Journal of the National Cancer Institute (1988)

Findings from this population-based study in Los Angeles County suggest, for the first time, that tumors of the parotid gland are related to prior exposure to diagnostic medical and dental radiography. Responses to interviews with 408 patients with a parotid tumor (269 benign tumors and 139 malignant tumors) were compared to responses of 408 neighborhood controls. Cumulative exposure of the parotid gland from diagnostic radiography was associated with a dose-related increase in risk of malignant tumors (P for trend <.05; relative risk for exposure to ≥50 rad = 3.4; 95% confidence interval = 1.02–11.46). Benign tumors showed a weaker positive association, and exposure before age 20 to a major diagnostic examination (full-mouth or panoramic dental radiography or medical radiography to the head) increased risk (relative risk = 1.8; confidence interval = 1.13–2.91). This study also confirmed the association of malignant tumors with prior radiation treatment to the head or neck; 28% of these tumors are attributable to exposure of the parotid gland from diagnostic and therapeutic radiation. [J Natl Cancer Inst 1988;80:943–949]