tbuckley/cabot-search huggingface dataset:
Different Protein Tyrosine Kinases Are Required for B Cell Antigen Receptor–mediated Activation of Extracellular Signal–Regulated kinase, c-Jun NH2-terminal Kinase 1, and p38 Mitogen-activated Protein Kinase
Authors: Aimin Jiang, Andrew Craxton, Tomohiro Kurosaki, Edward A. Clark
Journal: The Journal of Experimental Medicine (1998)

B cell antigen receptor (BCR) cross-linking activates three distinct families of nonreceptor protein tyrosine kinases (PTKs): src-family kinases, Syk, and Btk; these PTKs are responsible for initiating downstream events. BCR cross-linking in the chicken DT40 B cell line also activates three distinct mitogen-activated protein kinases (MAPKs): extracellular signal–regulated kinase (ERK)2, c-jun NH2-terminal kinase (JNK)1, and p38 MAPK. To dissect the functional roles of these PTKs in MAPK signaling, activation of MAPKs was examined in various PTK-deficient DT40 cells. BCR-mediated activation of ERK2, although maintained in Lyn-deficient cells, was abolished in Syk-deficient cells and partially inhibited in Btk-deficient cells, indicating that BCR-mediated ERK2 activation requires Syk and that sustained ERK2 activation requires Btk. BCR-mediated JNK1 activation was maintained in Lyn-deficient cells but abolished in both Syk- and Btk-deficient cells, suggesting that JNK1 is activated via a Syk- and Btk-dependent pathway. Consistent with this, BCR-mediated JNK1 activation was dependent on intracellular calcium and phorbol myristate acetate–sensitive protein kinase Cs. In contrast, BCR-mediated p38 MAPK activation was detected in all three PTK-deficient cells, suggesting that no single PTK is essential. However, BCR-mediated p38 MAPK activation was abolished in Lyn/Syk double deficient cells, demonstrating that either Lyn or Syk alone may be sufficient to activate p38 MAPK. Our data show that BCR-mediated MAPK activation is regulated at the level of the PTKs.
The β <sub>2</sub> -Adrenergic Receptor Delivers an Antiapoptotic Signal to Cardiac Myocytes Through G <sub>i</sub> -Dependent Coupling to Phosphatidylinositol 3′-Kinase
Authors: Alan Chesley, Martha S. Lundberg, Toshinobu Asai, Rui-Ping Xiao, Seiji Ohtani, Edward G. Lakatta, Michael T. Crow
Journal: Circulation Research (2000)

Abstract —Recent studies have shown that chronic β-adrenergic receptor (β-AR) stimulation alters cardiac myocyte survival in a receptor subtype-specific manner. We examined the effect of selective β 1 - and β 2 -AR subtype stimulation on apoptosis induced by hypoxia or H 2 O 2 in rat neonatal cardiac myocytes. Although neither β 1 - nor β 2 -AR stimulation had any significant effect on the basal level of apoptosis, selective β 2 -AR stimulation protected myocytes from apoptosis. β 2 -AR stimulation markedly increased mitogen-activated protein kinase/extracellular signal–regulated protein kinase (MAPK/ERK) activation as well as phosphatidylinositol-3′-kinase (PI-3K) activity and Akt/protein kinase B phosphorylation. β 1 -AR stimulation also markedly increased MAPK/ERK activation but only minimally activated PI-3K and Akt. Pretreatment with pertussis toxin blocked β 2 -AR–mediated protection from apoptosis as well as the β 2 -AR–stimulated changes in MAPK/ERK, PI-3K, and Akt/protein kinase B. The selective PI-3K inhibitor, LY 294002, also blocked β 2 -AR–mediated protection, whereas inhibition of MAPK/ERK activation at an inhibitor concentration that blocked agonist-induced activation but not the basal level of activation had no effect on β 2 -AR–mediated protection. These findings demonstrate that β 2 -ARs activate a PI-3K–dependent, pertussis toxin–sensitive signaling pathway in cardiac myocytes that is required for protection from apoptosis-inducing stimuli often associated with ischemic stress.
Association of adiponectin multimers with Barrett's oesophagus
Authors: J. H. Rubenstein, J. Y. Kao, R. D. Madanick, M. Zhang, M. Wang, M. B. Spacek, J. L. Donovan, S. D. Bright, N. J. Shaheen
Journal: Gut (2009)

<h3>Objective:</h3> Barrett’s oesophagus is associated with abdominal obesity. Adiponectin is a peptide that is secreted from adipocytes and circulates in three multimeric forms: low molecular weight (LMW), middle molecular weight (MMW), and high molecular weight (HMW). The anti-inflammatory effects of adiponectin are specific to individual multimers, with LMW being most anti-inflammatory. We postulated that circulating levels of adiponectin and its multimers would be associated with the risk of Barrett’s oesophagus. <h3>Design:</h3> Cross-sectional study. <h3>Setting:</h3> Outpatient clinic in North Carolina, USA. <h3>Patients:</h3> Cases of Barrett’s oesophagus and controls undergoing upper endoscopy for gastro-oesophageal reflux disease (GORD). <h3>Main outcome measures:</h3> Adjusted odds ratios of plasma adiponectin levels and its multimers for Barrett’s oesophagus. <h3>Results:</h3> There were 112 cases of Barrett’s oesophagus and 199 GORD controls. Total adiponectin was not associated with Barrett’s oesophagus (3<sup>rd</sup> tertile vs 1<sup>st</sup> tertile adjusted odds ratio (aOR) = 0.88; 95% confidence interval (CI) = 0.44 to 1.78). High levels of LMW adiponectin were associated with a decreased risk of Barrett’s oesophagus (3<sup>rd</sup> tertile vs 1<sup>st</sup> tertile aOR = 0.33; 95% CI, 0.16 to 0.69), and a high LMW/total ratio appeared particularly inversely associated with Barrett’s oesophagus (3<sup>rd</sup> tertile vs 1<sup>st</sup> tertile aOR = 0.27; 95% CI, 0.13 to 0.58). <h3>Conclusions:</h3> High levels of LMW adiponectin are associated with a decreased risk of Barrett’s oesophagus among patients with GORD. Further human studies are required to confirm these findings, and in vitro studies are needed to understand if there is a mechanism whereby adiponectin may affect Barrett’s metaplasia.
Hyperglycemia Is Associated With Adverse Outcomes in Patients Receiving Total Parenteral Nutrition
Authors: N. Wah Cheung, Brett Napier, Cathy Zaccaria, John P. Fletcher
Journal: Diabetes Care (2005)

OBJECTIVE—Hyperglycemia is associated with poor clinical outcomes and mortality in myocardial infarction, stroke, and general hospital patients. However, there are few data regarding the effect of hyperglycemia on outcomes in patients receiving total parenteral nutrition (TPN), a therapy that predisposes patients to hyperglycemia. The aim of this study was to determine whether elevated blood glucose levels are associated with adverse outcomes in patients receiving TPN. RESEARCH DESIGN AND METHODS—A retrospective analysis was undertaken from the medical records of 111 patients (122 treatment episodes) receiving TPN. All patients had blood drawn daily for the measurement of blood glucose levels. Outcome measures were assessed as a function of mean daily blood glucose levels while receiving TPN. RESULTS—Increased blood glucose levels were associated with an increased risk of cardiac complications (odds ratio 1.61, 95% CI 1.09–2.37, P = 0.02), infection (1.4, 1.08–1.82, P = 0.01), systemic sepsis (1.36, 1.00–1.86, P = 0.05), acute renal failure (1.47, 1.00–2.17, P = 0.05), and death (1.77, 1.23–2.52, P &amp;lt; 0.01). When the data were examined by quartiles of blood glucose levels, the mortality of subjects in the highest quartile was 10.9 times (95% CI 2.0–60.5, P &amp;lt; 0.01) that of subjects in the lowest quartile, and the risk of developing any complication was 4.3 times higher (1.4–13.1, P &amp;lt; 0.01). These effects were independent of age, sex, or prior diabetes status. CONCLUSIONS—Hyperglycemia is a predictor of poor outcomes in patients receiving TPN. The confirmation of a relation between blood glucose levels and adverse outcomes provides support for tight glycemic control in these patients.
Kidney Transplantation from Living Unrelated Donors
Authors: J. Michael Cecka
Journal: Annual Review of Medicine (2000)

Kidney transplant candidates increasingly are looking to their relatives, spouses, and even friends for a better chance at transplantation. The wait for a cadaver kidney might be 2–5 years. Although kidneys from well-matched family members have been transplanted with excellent results for many years, accepting living donors who are genetically unrelated to the patient has not been encouraged until recently. Results show that, among 1700 patients who received kidney transplants from living unrelated donors in the United States from 1995 through 1998, the one- and projected ten-year graft survival rates were 92% and 67%, respectively. These results are superior to the 87% and 50% rates for more than 26,000 cadaver kidney transplants during the same period. Risks to the donor are low (&lt;0.005% mortality and &lt;0.3% serious complications) but not absent. Thus, motivated spouses, friends, and adopted or stepfamily members can play an important role in the rehabilitation of patients who need a kidney transplant.
Atypical adenomatous hyperplasia of the lung: a clinicopathological study of 118 cases including cases with multiple atypical adenomatous hyperplasia
Authors: R Nakahara
Journal: Thorax (2001)

<h3>Abstract</h3> <h3>Background</h3> Single-cell transcriptome (SCT) sequencing technology has reached the level of high-throughput technology where gene expression can be measured concurrently from large numbers of cells. The results of gene expression studies are highly reproducible when strict protocols and standard operating procedures (SOP) are followed. However, differences in sample processing conditions result in significant changes in gene expression profiles making direct comparison of different studies difficult. Unsupervised machine learning (ML) uses clustering algorithms combined with semi-automated cell labeling and manual annotation of individual cells. They do not scale up well and a workflow used on a specific dataset will not perform well with other studies. Supervised ML classification shows superior classification accuracy and generalization properties as compared to unsupervised ML methods. We describe a supervised ML method that deploys artificial neural networks (ANN), for 5-class classification of healthy peripheral blood mononuclear cells (PBMC) from multiple diverse studies. <h3>Results</h3> We used 58 data sets to train ANN incrementally – over ten cycles of training and testing. The sample processing involved four protocols: separation of PBMC, separation of PBMC + enrichment (by negative selection), separation of PBMC + FACS, and separation of PBMC + MACS. The training data set included between 85 and 110 thousand cells, and the test set had approximately 13 thousand cells. Training and testing were done with various combinations of data sets from four principal data sources. The overall accuracy of classification on independent data sets reached 5-class classification accuracy of 94%. Classification accuracy for B cells, monocytes, and T cells exceeded 95%. Classification accuracy of natural killer (NK) cells was 75% because of the similarity between NK cells and T cell subsets. The accuracy of dendritic cells (DC) was low due to very low numbers of DC in the training sets. <h3>Conclusions</h3> The incremental learning ANN model can accurately classify the main types of PBMC. With the inclusion of more DC and resolving ambiguities between T cell and NK cell gene expression profiles, we will enable high accuracy supervised ML classification of PBMC. We assembled a reference data set for healthy PBMC and demonstrated a proof-of-concept for supervised ANN method in classification of previously unseen SCT data. The classification shows high accuracy, that is consistent across different studies and sample processing methods.
Occurrence of acute lower limb injuries in artistic gymnasts in relation to event and exercise phase
Authors: P Kirialanis, P Malliou, A Beneka, K Giannakopoulos
Journal: British Journal of Sports Medicine (2003)

To record the incidence of lower limb injuries (acute and overuse syndromes) in Greek artistic gymnasts in relation to the event and exercise phase.A total of 162 gymnasts (83 male and 79 female athletes) participating in the Greek artistic gymnastic championships were observed weekly for the 1999-2000 season.Ninety three (61.6%) acute injuries and 58 (38.4%) overuse syndromes were recorded. The most common anatomical location was the ankle (69 cases, 45.7%), followed by the knee (40 cases, 26.5%). The rate of mild injuries was 26.6% (25 cases), that of moderate injuries was 44% (41 cases), and that of major injuries was 29% (27 cases). The incidence of injury to the ankle and knee was significantly higher in the floor exercise, especially during the landing phase, than in the other events.By its nature, gymnastics predisposes to acute injuries, but up to 75% are mild or moderate. Special attention should be paid to the floor exercise, especially the landing phase.
Glycoprotein 130 regulates bone turnover and bone size by distinct downstream signaling pathways
Authors: Natalie A. Sims, Brendan J. Jenkins, Julian M.W. Quinn, Akira Nakamura, Markus Glatt, Matthew T. Gillespie, Matthias Ernst, T. John Martin
Journal: Journal of Clinical Investigation (2004)

The gp130-dependent cytokines, which signal through at least two intracellular pathways, regulate osteoclast and osteoblast formation. To define their roles in regulating bone mass, we analyzed mice in which gp130 signaling via either the signal transducer and activator of transcription (STAT) 1/3 (gp130ΔSTAT/ΔSTAT) or SHP2/ras/MAPK (gp130Y757F/Y757F) pathway was attenuated. In gp130ΔSTAT/ΔSTAT mice, trabecular bone volume (BV/TV) and turnover were normal, but bone length was reduced by premature growth plate closure, indicating an essential role for gp130-STAT1/3 signaling in chondrocyte differentiation. In contrast, while bone size was normal in gp130Y757F/Y757F mice, BV/TV was reduced due to high bone turnover, indicated by high osteoclast surface/bone surface (OcS/BS) and osteoblast surface/bone surface (ObS/BS). Furthermore, generation of functional osteoclasts from bone marrow of gp130Y757F/Y757F mice was elevated, revealing that while gp130 family cytokines stimulate osteoclastogenesis through the osteoblast lineage, gp130, via SHP2/Ras/MAPK, inhibits osteoclastogenesis in a cell lineage–autonomous manner. Genetic ablation of IL-6 in gp130Y757F/Y757F mice exacerbated this osteopenia by reducing ObS/BS without affecting OcS/BS. Thus, while IL-6 is critical for high bone formation in gp130Y757F/Y757F mice, it is not involved in the increased osteoclastogenesis. In conclusion, gp130 is essential for normal bone growth and trabecular bone mass, with balanced regulation depending on selective activation of STAT1/3 and SHP2/ras/MAPK, respectively. Furthermore, the latter pathway can directly inhibit osteoclastogenesis in vivo.
2004 consensus statements on the management of ovarian cancer: final document of the 3rd International Gynecologic Cancer Intergroup Ovarian Cancer Consensus Conference (GCIG OCCC 2004)
Authors: A. du Bois, M. Quinn, T. Thigpen, J. Vermorken, E. Avall-Lundqvist, M. Bookman, D. Bowtell, M. Brady, A. Casado, A. Cervantes, E. Eisenhauer, M. Friedlaender, K. Fujiwara, S. Grenman, J.P. Guastalla, P. Harper, T. Hogberg, S. Kaye, H. Kitchener, G. Kristensen, R. Mannel, W. Meier, B. Miller, J.P. Neijt, A. Oza, R. Ozols, M. Parmar, S. Pecorelli, J. Pfisterer, A. Poveda, D. Provencher, E. Pujade-Lauraine, M. Randall, J. Rochon, G. Rustin, S. Sagae, F. Stehman, G. Stuart, E. Trimble, P. Vasey, I. Vergote, R. Verheijen, U. Wagner
Journal: Annals of Oncology (2005)
Systolic anterior motion in the absence of asymmetric septal hypertrophy. A buckling phenomenon of the chordae tendineae.
Authors: J M Gardin, J V Talano, L Stephanides, J Fizzano, M Lesch
Journal: Circulation (1981)

Systolic anterior motion (SAM) of the mitral valve in the absence of asymmetric septal hypertrophy or concentric left ventricular hypertrophy has been reported in several conditions. In this report we describe the clinical and echocardiographic findings in 15 patients who demonstrated SAM without associated organic heart disease (group 1, 10 patients) or in association with mitral valve prolapse (group 2, five patients). Cross-sectional echocardiography revealed the etiology of SAM in both groups to be early systolic anterior angular motion ("buckling") of mitral chordal structures, rather than movement of the body of the anterior mitral leaflet into the left ventricular outflow tract. In contrast to normal subjects and group 1, group 2 patients had auscultatory evidence of mitral prolapse, a slightly greater mean left ventricular ejection fraction (p < 0.05) (normals, 69 +/- 5.2%, group 1, 72 +/- 3.8%, group 2, 75+/- 5.6%), and a greater mean diastolic mitral valve (D-E) excursion (p < 0.05) (normals, 1.8 +/- 0.2 cm, group 1, 2.2 +/- 0.3 cm, and group 2, 2.6 +/- 0.4 cm). This spectrum of mitral excursion and left ventricular ejection fraction supports the concept that the mitral valve prolapse syndrome may have as its basis a mitral valve abnormality and/or a hyperdynamic state that predispose to both chordal buckling and mitral leaflet prolapse.
Attenuation of the Retinoblastoma Pathway in Pancreatic Neuroendocrine Tumors Due to Increased Cdk4/Cdk6
Authors: Laura H. Tang, Tanupriya Contractor, Richard Clausen, David S. Klimstra, Yi-Chieh Nancy Du, Peter J. Allen, Murray F. Brennan, Arnold J. Levine, Chris R. Harris
Journal: Clinical Cancer Research (2012)

In mice, genetic changes that inactivate the retinoblastoma tumor suppressor pathway often result in pancreatic neuroendocrine tumors (Pan-NETs). Conversely, in humans with this disease, mutations in genes of the retinoblastoma pathway have rarely been detected, even in genome-wide sequencing studies. In this study, we took a closer look at the role of the retinoblastoma pathway in human Pan-NETs.Pan-NET tumors from 92 patients were subjected to immunohistochemical staining for markers of the retinoblastoma pathway. To search for amplifications of retinoblastoma pathway genes, genomic DNAs from 26 tumors were subjected to copy number analysis. Finally, a small-molecule activator of the retinoblastoma pathway was tested for effects on the growth of two Pan-NET cell lines.A majority of tumors expressed high amounts of Cdk4 or its partner protein cyclin D1. High amounts of phosphorylated Rb1 were present in tumors that expressed high levels of Cdk4 or cyclin D1. The copy numbers of Cdk4 or the analogous kinase gene Cdk6 were increased in 19% of the tumors. Growth of the human Pan-NET cell line QGP1 was inhibited in a xenograft mouse model by the Cdk4/6 inhibitor, PD 0332991, which reactivates the retinoblastoma pathway.Inactivation of the retinoblastoma pathway was indicated for most Pan-NETs. Gene amplification and overexpression of Cdk4 and Cdk6 suggests that patients with Pan-NETs may respond strongly to Cdk4/6 inhibitors that are entering clinical trials.
Systematic review of randomised controlled trials of interventions for painful shoulder: selection criteria, outcome assessment, and efficacy
Authors: S. Green, R. Buchbinder, R. Glazier, A. Forbes
Journal: BMJ (1998)

<h3>Abstract</h3> <b>Objective:</b> To review the efficacy of common interventions for shoulder pain. <b>Design:</b> All randomised controlled trials of non-steroidal anti-inflammatory drugs, intra-articular and subacromial glucocorticosteroid injection, oral glucocorticosteroid treatment, physiotherapy, manipulation under anaesthesia, hydrodilatation, and surgery for shoulder pain that were identified by computerised and hand searches of the literature and had a blinded assessment of outcome were included. <b>Main outcome measures:</b> Methodological quality (score out of 40), selection criteria, and outcome measures. Effect sizes were calculated and combined in a pooled analysis if study population, end point, and intervention were comparable. <b>Results:</b> Thirty one trials met inclusion criteria. Mean methodological quality score was 16.8 (9.5-22). Selection criteria varied widely, even for the same diagnostic label. There was no uniformity in the outcome measures used, and their measurement properties were rarely reported. Effect sizes for individual trials were small (range −1.4 to 3.0). The results of only three studies investigating “rotator cuff tendinitis” could be pooled. The only positive finding was that subacromial steroid injection is better than placebo in improving the range of abduction (weighted difference between means 35° (95% confidence interval 14 to 55)). <b>Conclusions:</b> There is little evidence to support or refute the efficacy of common interventions for shoulder pain. As well as the need for further well designed clinical trials, more research is needed to establish a uniform method of defining shoulder disorders and developing outcome measures which are valid, reliable, and responsive in affected people. <h3>Key messages</h3> This systematic review found little evidence to support the use of any of the common interventions in managing shoulder pain There is currently no uniformity in the way shoulder disorders are labelled or defined Measurement of outcome varies widely between clinical trials and, in general, the reliability, validity, and responsiveness of these outcome measures are not established Further clinical trials are needed to determine the optimal treatment strategies for shoulder pain
Monoclonal B lymphocytes with the characteristics of “indolent” chronic lymphocytic leukemia are present in 3.5% of adults with normal blood counts
Authors: Andy C. Rawstron, Michael J. Green, Anita Kuzmicki, Ben Kennedy, James A. L. Fenton, Paul A. S. Evans, Sheila J. M. O'Connor, Stephen J. Richards, Gareth J. Morgan, Andrew S. Jack, Peter Hillmen
Journal: Blood (2002)
Toxicity Assessments of Near-infrared Upconversion Luminescent LaF<sub>3</sub>:Yb,Er in Early Development of Zebrafish Embryos
Authors: Kan Wang, Jiebing Ma, Meng He, Guo Gao, Hao Xu, Jie Sang, Yuxia Wang, Baoquan Zhao, Daxiang Cui
Journal: Theranostics (2013)

This study reports the effects of upconversion nanoparticles (UCNPs) LaF 3 :Yb,Er on zebrafish, with the aim of investigating UCNPs toxicity.LaF 3 :Yb,Er were prepared by an oleic acid/ionic liquid two-phase system, and characterized by transmission electron microscope and X-ray powder diffraction.140 zebrafish embryos were divided into six test groups and one control group, and respectively were injected into 5, 25, 50, 100, 200, 400 µg/mL LaF 3 :Yb,Er@SiO 2 solution, and respectively were raised for 5 days.Each experiment was repeated ten times.Results showed that water-soluble LaF 3 :Yb,Er were successfully prepared, and did not exhibit obvious toxicity to zebrafish embryos under 100 µg/mL, but exhibited chronic toxicities 200 µg/mL in vivo, resulting in malformations and delayed hatching rate and embryonic and larval development.The excretion channels of LaF 3 :Yb,Er in adult zebrafish were mainly found in the intestine after being injected evenly for 24 h.In conclusion, the exploration of LaF 3 :Yb,Er for in vivo applications in animals and humans must consider UCNPs biocompatibility.