tbuckley/cabot-search huggingface dataset:
Characterization of Melanoma Cells Capable of Propagating Tumors from a Single Cell
Authors: Matthew A. Held, David P. Curley, David Dankort, Martin McMahon, Viswanathan Muthusamy, Marcus W. Bosenberg
Journal: Cancer Research (2010)

Questions persist about the nature and number of cells with tumor-propagating capability in different types of cancer, including melanoma. In part, this is because identification and characterization of purified tumorigenic subsets of cancer cells has not been achieved to date. Here, we report tumor formation after injection of single purified melanoma cells derived from three novel mouse models. Tumor formation occurred after every injection of individual CD34+p75- melanoma cells, with intermediate rates using CD34-p75- cells, and rarely with CD34-p75+ cells. These findings suggest that tumorigenic melanoma cells may be more common than previously thought and establish that multiple distinct populations of melanoma-propagating cells (MPC) can exist within a single tumor. Interestingly, individual CD34-p75- MPCs could regenerate cellular heterogeneity after tumor formation in mice or multiple passages in vitro, whereas CD34+p75- MPCs underwent self-renewal only, showing that reestablishment of tumor heterogeneity is not always a characteristic of individual cells capable of forming tumors. Functionally, single purified MPCs were more resistant to chemotherapy than non-MPCs. We anticipate that purification of these MPCs may allow a more comprehensive evaluation of the molecular features that define tumor-forming capability and chemotherapeutic resistance in melanoma.
Altered hip and trunk muscle function in individuals with patellofemoral pain
Authors: S M Cowan, K M Crossley, K L Bennell
Journal: British Journal of Sports Medicine (2008)

Objective: The purpose of this study was to investigate the role of hip muscles in patellofemoral pain (PFP), specifically by investigating neuromotor control, strength and range of motion of the hip muscles. Design: Cross-sectional. Setting: University laboratory. Patients: Ten participants diagnosed with PFP and 27 asymptomatic controls were recruited, using standard inclusion and exclusion criteria. Main outcome measures: Electromyographic activity of the vasti and anterior gluteus medius (GM) were recorded using surface electrodes and posterior GM using fine wire electrodes while the participant completed a stair-stepping task. Hip strength and trunk side flexion strength was assessed using a hand-held dynamometer and hip range of motion with an inclinometer. Pain and disability measures were recorded for the PFP participants. Results: When individuals with PFP completed the stair-stepping task there was a delay in activation of both anterior and posterior GM (p&lt;0.02) and an alteration in vasti control (p = 0.001). In addition, trunk side flexion strength was significantly less (29%) in individuals with PFP (p = 0.03). Conclusion: This study provides evidence that trunk side flexion strength and neuromotor control of the GM are affected in people with PFP. This study also confirms the presence of a delayed vastus medialis obliquus relative to vastus lateralis, providing further evidence underpinning the importance of retraining the vasti function in patients with PFP.
Diseases of the Gastrointestinal Tract
Authors: Garnett Cheney, Claude P. Callaway
Journal: Annual Review of Medicine (1953)

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of coronavirus disease 2019 (COVID-19), emerged in China in December 2019 and quickly spread around the globe, killing more than 4 million people and causing a severe economic crisis. ...Read More
Subnormal sensitivity of neutrophils to complement split product C5a in rheumatoid arthritis: relation to complement catabolism and disease extent.
Authors: J Elmgreen, T M Hansen
Journal: Annals of the Rheumatic Diseases (1985)

The capacity of circulating neutrophils for activation by complement was studied in outpatients with classical or definite rheumatoid arthritis during treatment with dextropropoxyphene only. Analysis of dose-response in the Boyden chamber assay of chemotaxis showed that sensitivity to the potent, complement derived anaphylatoxin, C5a, was markedly decreased, especially in those patients with few joints involved. In contrast, peak response to C5a was within the normal range. Increased complement 3c split products in plasma of the patients suggested involvement of complement cascade reactions. Subnormal sensitivity of neutrophils to phlogistic mediators released by complement may tend to limit their recruitment and potentially tissue destroying secretion locally in rheumatoid arthritis.
Adult pilocytic astrocytomas: clinical features and molecular analysis
Authors: Brett J. Theeler, Benjamin Ellezam, Zsila S. Sadighi, Vidya Mehta, M. Diep Tran, Adekunle M. Adesina, Janet M. Bruner, Vinay K. Puduvalli
Journal: Neuro-Oncology (2014)

Adult pilocytic astrocytomas (PAs) are rare and have an aggressive clinical course compared with pediatric patients. Constitutive Ras/RAF/MAPK signaling appears to be an important oncogenic event in sporadic PA. We evaluated clinical data and molecular profiles of adult PAs at our institution. We identified 127 adult PAs in our institutional database. Cases with available tissue were tested for BRAF-KIAA1549 fusion/duplication (B-K fusion) by fluorescence in situ hybridization and submitted for mutation profiling using the Sequenom mutation profiling panel. Subgroup analyses were performed based on clinical and molecular data. The majority of adult PAs are supratentorial. Twenty-two percent of cases had an initial pathologic diagnosis discordant with the diagnosis made at our institution. Recurrence was seen in 42% of cases, and 13% of patients died during follow-up. Adjuvant radiotherapy following surgical resection was associated with a statistically significant decrease in progression-free survival (P = .004). B-K fusion was identified in 20% (9 of 45) of patients but was not associated with outcome. No BRAF V600E mutations (0 of 40 tested) were found. This was the largest single institution series of adult PA. A significant proportion of adult PAs follow an aggressive clinical course. Our results support a period of observation following biopsy or surgical resection. B-K fusion in adult PA does not influence outcome, and BRAF V600E mutation appears to be a very rare event. Further study of tumor biology and optimal treatment is needed, given a more aggressive clinical behavior.
Single-Nucleotide Polymorphisms Inside MicroRNA Target Sites Influence Tumor Susceptibility
Authors: Milena S. Nicoloso, Hao Sun, Riccardo Spizzo, Hyunsoo Kim, Priyankara Wickramasinghe, Masayoshi Shimizu, Sylwia E. Wojcik, Jana Ferdin, Tanja Kunej, Lianchun Xiao, Siranoush Manoukian, Giorgio Secreto, Fernando Ravagnani, Xuemei Wang, Paolo Radice, Carlo M. Croce, Ramana V. Davuluri, George A. Calin
Journal: Cancer Research (2010)

Single-nucleotide polymorphisms (SNP) associated with polygenetic disorders, such as breast cancer (BC), can create, destroy, or modify microRNA (miRNA) binding sites; however, the extent to which SNPs interfere with miRNA gene regulation and affect cancer susceptibility remains largely unknown. We hypothesize that disruption of miRNA target binding by SNPs is a widespread mechanism relevant to cancer susceptibility. To test this, we analyzed SNPs known to be associated with BC risk, in silico and in vitro, for their ability to modify miRNA binding sites and miRNA gene regulation and referred to these as target SNPs. We identified rs1982073-TGFB1 and rs1799782-XRCC1 as target SNPs, whose alleles could modulate gene expression by differential interaction with miR-187 and miR-138, respectively. Genome-wide bioinformatics analysis predicted approximately 64% of transcribed SNPs as target SNPs that can modify (increase/decrease) the binding energy of putative miRNA::mRNA duplexes by >90%. To assess whether target SNPs are implicated in BC susceptibility, we conducted a case-control population study and observed that germline occurrence of rs799917-BRCA1 and rs334348-TGFR1 significantly varies among populations with different risks of developing BC. Luciferase activity of target SNPs, allelic variants, and protein levels in cancer cell lines with different genotypes showed differential regulation of target genes following overexpression of the two interacting miRNAs (miR-638 and miR-628-5p). Therefore, we propose that transcribed target SNPs alter miRNA gene regulation and, consequently, protein expression, contributing to the likelihood of cancer susceptibility, by a novel mechanism of subtle gene regulation.
Bifocal intracranial tumors of nongerminomatous germ cell etiology: diagnostic and therapeutic implications
Authors: A. A. Aizer, R. V. Sethi, E. T. Hedley-Whyte, D. Ebb, N. J. Tarbell, T. I. Yock, S. M. MacDonald
Journal: Neuro-Oncology (2013)

Patients presenting with synchronous bifocal intracranial tumors (masses in the pineal and neurohypophyseal region), detectable human chorionic gonadotropin (hCG) levels (5–100 mIU/mL), and normal alpha feto-protein (AFP) levels (≤10 ng/mL) are often diagnosed empirically with pure germinoma. In such scenarios, pathologic confirmation is often deferred, given that bifocal nongerminomatous germ cell tumors (NGGCTs) are considered rare and because available literature and research protocols support such an approach. We sought to characterize the association between bifocal intracranial tumors and NGGCT histology. Seventy-one patients treated for intracranial germ cell tumors at Massachusetts General Hospital in 1998–2012 were identified. Patients presenting with synchronous bifocal disease were selected for further review. Of the 71 patients presenting with intracranial germ cell tumors, 14 (19.7%) had synchronous bifocal disease. Of these 14 patients, 7 (50.0%) had germinoma, 3 (21.4%) had NGGCT, and 4 (28.6%) had hCG levels <200 mIU/mL and normal AFP levels and were treated without pathologic confirmation. Of the 3 patients with confirmed bifocal NGGCT, 2 had detectable hCG levels with AFP <10 ng/mL and 1 patient had a detectable hCG level with a modest elevation in AFP. NGGCTs should be considered in the differential diagnosis for patients presenting with bifocal intracranial tumors. Given differences in the management of germinomas and NGGCTs, clinicians should strongly consider a biopsy in patients presenting with bifocal masses and normal or modestly elevated biomarkers. Misclassification of such cases as germinomas could result in undertreatment and a possible increased risk for recurrence.
Oesophageal high-resolution manometry: moving from research into clinical practice
Authors: M R Fox, A J Bredenoord
Journal: Gut (2007)

Manometry measures pressure within the oesophageal lumen and sphincters, and provides an assessment of the neuromuscular activity that dictates function in health and disease. It is performed to investigate the cause of functional dysphagia, unexplained “non-cardiac” chest pain, and in the pre-operative work-up of patients referred for anti-reflux surgery. Manometric techniques have improved in a step-wise fashion from a single pressure channel to the development of high-resolution manometry (HRM) with up to 36 pressure sensors. At the same time, advances in computer processing allow pressure data to be presented in real time as a compact, visually intuitive “spatiotemporal plot” of oesophageal pressure activity. HRM recordings reveal the complex functional anatomy of the oesophagus and its sphincters. Spatiotemporal plots provide objective measurements of the forces that move food and fluid from the pharynx to the stomach and determine the risk of reflux events. The introduction of commercially available HRM has been followed by rapid uptake of the technique. This review examines the current evidence that supports the move of HRM from the research setting into clinical practice. It is assessed whether a detailed description of pressure activity identifies clinically relevant oesophageal dysfunction that is missed by conventional investigation, increasing diagnostic yield and accuracy. The need for a new classification system for oesophageal motor activity based on HRM recordings is discussed. Looking ahead the potential of this technology to guide more effective medical and surgical treatment of oesophageal disease is considered because, ultimately, it is this that will define the success of HRM in clinical practice.
Fludarabine, Melphalan, and Alemtuzumab Conditioning in Adults With Standard-Risk Advanced Acute Myeloid Leukemia and Myelodysplastic Syndrome
Authors: Koen van Besien, A. Artz, S. Smith, D. Cao, S. Rich, L. Godley, D. Jones, P. Del Cerro, D. Bennett, B. Casey, O. Odenike, M. Thirman, C. Daugherty, A. Wickrema, T. Zimmerman, R.A. Larson, W. Stock
Journal: Journal of Clinical Oncology (2005)

This prospective phase II study evaluated toxicity, relapse rate, progression-free survival, and overall survival after allogeneic transplantation and conditioning with fludarabine, melphalan, and alemtuzumab in patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS).Fifty-two consecutive adults with AML and MDS were enrolled onto the study. Median age was 52 years (range, 17 to 71 years) and the majority of patients had high-risk disease, comorbidities, and/or modest reduction in performance status. Fifty-six percent of patients had unrelated or mismatched related donors.After a median follow-up of 18 months (range, 2 to 34 months), 1-year survival was 48% (95% CI, 34% to 61%), progression-free survival was 38% (95% CI, 25% to 52%), relapse rate was 27% (95% CI, 15% to 40%), and treatment-related mortality was 33% (95% CI, 20% to 46%). The cumulative probability of extensive chronic graft-versus-host disease (GVHD) was only 18% (95% CI, 8% to 40%); extensive chronic GVHD was only observed in recipients of unrelated donor transplants. Performance score and disease status were the major predictors of outcome. High-risk disease (ie, active AML or MDS with > 5% blasts) or even modest decreases in performance status were associated with poor outcomes. Patients with standard-risk leukemia (first or second complete remission) or MDS (< 5% blasts) had excellent outcomes despite unfavorable disease characteristics.Fludarabine and melphalan combined with in vivo alemtuzumab is a promising transplantation regimen for patients with AML or MDS and low tumor burden. For patients with active disease, this regimen provides at best modest palliation. Despite a low incidence of GVHD, transplantation is still associated with considerable nonrelapse mortality in patients with decreased performance status.
Treatment exhaustion of highly active antiretroviral therapy (HAART) among individuals infected with HIV in the United Kingdom: multicentre cohort study
Authors: Caroline A Sabin, Teresa Hill, Fiona Lampe, Ryanne Matthias, Sanjay Bhagani, Richard Gilson, Mike S Youle, Margaret A Johnson, Martin Fisher, George Scullard, Philippa Easterbrook, Brian Gazzard, Andrew N Phillips
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To investigate whether there is evidence that an increasing proportion of HIV infected patients is starting to experience increases in viral load and decreases in CD4 cell count that are consistent with exhaustion of available treatment options. <b>Design</b> Multicentre cohort study. <b>Setting</b> Six large HIV treatment centres in southeast England. <b>Participants</b> All individuals seen for care between 1 January 1996 and 31 December 2002. <b>Main outcome measures</b> Exposure to individual antiretroviral drugs and drug classes, CD4 count, plasma HIV RNA burden. <b>Results</b> Information is available on 16 593 individuals (13 378 (80.6%) male patients, 10 340 (62.3%) infected via homosexual or bisexual sex, 4426 (26.7%) infected via heterosexual sex, median age 34 years). Overall, 10 207 of the 16 593 patients (61.5%) have been exposed to any antiretroviral therapy. This proportion increased from 41.2% of patients under follow up at the end of 1996 to 71.3% of those under follow up in 2002. The median CD4 count and HIV RNA burden of patients under follow up in each year changed from 270 cells/mm<sup>3</sup> and 4.34 log<sub>10</sub> copies/ml in 1996 to 408 cells/mm<sup>3</sup> and 1.89 log<sub>10</sub> copies/ml, respectively, in 2002. By 2002, 3060 (38%) of patients who had ever been treated with antiretroviral therapy had experienced all three main classes. Of these, around one quarter had evidence of “viral load failure” with all these three classes. Patients with three class failure were more likely to have an HIV RNA burden &gt; 2.7 log<sub>10</sub> copies/ml and a CD4 count &lt; 200 cells/mm<sup>3</sup>. <b>Conclusions</b> The proportion of individuals with HIV infection in the United Kingdom who have been treated has increased gradually over time. A substantial proportion of these patients seem to be in danger of exhausting their options for antiretroviral treatment. New drugs with low toxicity, which are not associated with cross resistance to existing drugs, are urgently needed for such patients.
A fourth criterion for transient entrainment: the electrogram equivalent of progressive fusion.
Authors: R W Henthorn, K Okumura, B Olshansky, V J Plumb, P G Hess, A L Waldo
Journal: Circulation (1988)

Prior data pertaining to transient entrainment and associated phenomena have been best explained by pacing capture of a reentrant circuit. On this basis, we hypothesized that rapid pacing from a single site of two different constant pacing rates could constantly capture an appropriately selected bipolar electrogram recording site from one direction with a constant stimulus-to-electrogram interval during pacing at one rate, yet be constantly captured from another direction with a different constant stimulus-to-electrogram interval when pacing at a different constant pacing rate. To test this hypothesis, we studied a group of patients, each with a representative tachycardia (ventricular tachycardia, circus-movement tachycardia involving an atrioventricular bypass pathway, atrial tachycardia, and atrial flutter). For each tachycardia, pacing was performed from a single site for at least two different constant rates faster than the spontaneous rate of the tachycardia. We observed in these patients that a local bipolar recording site was constantly captured from different directions at two different pacing rates without interrupting the tachycardia at pacing termination. The evidence that the same site was captured from a different direction at two different pacing rates was supported by demonstrating a change in conduction time to that site associated with a change in the bipolar electrogram morphology at that site when comparing pacing at each rate. The mean conduction time (stimulus-to-recording site electrogram interval) was 319 +/- 69 msec while pacing at a mean cycle length of 265 +/- 50 msec, yet only 81 +/- 38 msec while pacing at a second mean cycle length of 233 +/- 51 msec, a mean change in conduction time of 238 +/- 56 msec. Remarkably, the faster pacing rate resulted in a shorter conduction time. The fact that the same electrode recording site was activated from different directions without interruption of the spontaneous tachycardia at pacing termination is difficult to explain on any mechanistic basis other than reentry. Also, these changes in conduction time and electrogram morphology occurred in parallel with the demonstration of progressive fusion beats on the electrocardiogram, the latter being an established criterion for transient entrainment.(ABSTRACT TRUNCATED AT 400 WORDS)
Calciphylaxis in chronic renal failure.
Authors: M N Budisavljevic, D Cheek, D W Ploth
Journal: Journal of the American Society of Nephrology (1996)

Calciphylaxis is a rare and life-threatening complication that is estimated to occur in 1% of patients with ESRD each year. Typically, extensive microvascular calcification and occlusion/thrombosis leads to violaceous skin lesions, which progress to nonhealing ulcers and sepsis. Secondary infection of skin lesions is common, often leading to sepsis and death. The lower extremities are predominantly involved (roughly 90% of patients). Patients with skin involvement over the trunk or proximal extremities have a poorer prognosis. Although most calciphylaxis patients have abnormalities of the calcium:phosphate axis or elevated levels of parathyroid hormone, these abnormalities do not appear to be fundamental to the pathophysiology of the disorder, and the etiology of calciphylaxis remains unclear. Recently, functional protein C deficiency has been hypothesized to cause a hypercoagulable state that could induce thrombosis in small vessels, with resulting skin ischemia, necrosis, and gangrene. The lack of understanding of the pathophysiology of the disease results in treatments that are equally unsatisfactory. Patients who undergo parathyroidectomy have a tendency to improve, but the prognosis for the disease is poor and mortality remains high.
Inflammatory and Prothrombotic Markers and the Progression of Renal Disease in Elderly Individuals
Authors: Linda Fried, Cam Solomon, Michael Shlipak, Stephen Seliger, Catherine Stehman-Breen, Anthony J. Bleyer, Paolo Chaves, Curt Furberg, Lewis Kuller, Anne Newman
Journal: Journal of the American Society of Nephrology (2004)

Inflammatory and prothrombotic markers are elevated in individuals with mild to moderate renal disease. It was hypothesized that these markers may also be determinants of the progression of renal disease. The association of six markers-serum C-reactive protein (CRP), white blood cell (WBC) count, fibrinogen, factor VII, albumin, and hemoglobin-with subsequent elevations of creatinine and decline in estimated GFR in the Cardiovascular Health Study, a community-based cohort of elderly individuals, was analyzed. Linear regression was used to determine predictors of an annualized change in serum creatinine as the main outcome. Duration of follow-up was 7 yr for the original cohort and 4 yr for the more recently recruited black cohort. A total of 588 (12.7%) individuals had a decline in estimated GFR of at least 3 ml/min per yr per 1.73 m(2). Higher CRP (P < 0.001), WBC count (P < 0.001), fibrinogen (P < 0.001), and factor VII (P < 0.001) levels and lower albumin (P < 0.001) and hemoglobin levels (P < 0.001) were associated with a rise in creatinine, after adjusting for age. With additional adjustments for race, gender, baseline creatinine, systolic and diastolic BP, lipid levels, weight, and pack-years smoking, higher CRP, factor VII, fibrinogen, WBC count, and lower albumin and hemoglobin levels remained associated with a rise in creatinine. Similar results were found for decline in estimated GFR. The decline in GFR was greater with increasing number of inflammatory or prothrombotic markers that were above the median (below for hemoglobin and albumin). Inflammatory and prothrombotic markers are predictors for a change in kidney function in elderly individuals. Interventions that reduce inflammation might confer significant cardiovascular and renal benefits.