tbuckley/cabot-search huggingface dataset:
Autoimmunity-associated protein tyrosine phosphatase PEP negatively regulates IFN-α receptor signaling
Authors: Derek A. Holmes, Eric Suto, Wyne P. Lee, Qinglin Ou, Qian Gong, Hamish R.C. Smith, Patrick Caplazi, Andrew C. Chan
Journal: The Journal of Experimental Medicine (2015)

The protein tyrosine phosphatase PTPN22(C1858T) allelic polymorphism is associated with increased susceptibility for development of systemic lupus erythematosus (SLE) and other autoimmune diseases. PTPN22 (also known as LYP) and its mouse orthologue PEP play important roles in antigen and Toll-like receptor signaling in immune cell functions. We demonstrate here that PEP also plays an important inhibitory role in interferon-α receptor (IFNAR) signaling in mice. PEP co-immunoprecipitates with components of the IFNAR signaling complex. Pep−/− hematopoietic progenitors demonstrate increased IFNAR signaling, increased IFN-inducible gene expression, and enhanced proliferation and activation compared to Pep+/+ progenitors in response to IFN-α. In addition, Pep−/− mice treated with IFN-α display a profound defect in hematopoiesis, resulting in anemia, thrombocytopenia, and neutropenia when compared to IFN-α–treated Pep+/+ mice. As SLE patients carrying the PTPN22(C1858T) risk variant have higher serum IFN-α activity, these data provide a molecular basis for how type I IFNs and PTPN22 may cooperate to contribute to lupus-associated cytopenias.
Mitral Incompetence Caused by Disease of the Mural Cusp
Authors: P. G. F. NIXON, GEOFFREY H. WOOLER, LEO R. RADIGAN
Journal: Circulation (1959)

Mitral regurgitation can be caused by one or a combination of different anatomic lesions. Because of this the authors believe that the surgeon can be aided if the type of defect is known preoperatively. The present study of 240 patients with disease of the mitral valve revealed a significant number whose disease was limited to the mural cusp. Criteria for the bedside diagnosis of this type of mitral regurgitation are presented.
Late-breaking abstract: "Capsaicin-induced bronchoconstriction in passive sensitized human precision-cut lung slices is mast cell dependent"
Authors: Sharon Melissa Jiménez Delgado, Susann Schindler, katherina Sewald, Armin Braun
Journal: European Respiratory Journal (2014)

Mast Cells play an pivotal role in bronchial asthma, one of the most common chronic inflammatory diseases of the respiratory tract. Since dysfunction of the sensory nerve fibers have been associated with asthma, the impact of neuronal stimulation on bronchoconstriction and mast cell degranulation were analysed.  Mast cells and peripheral sensory nerves were visualized using a primary antibody against tryptase and the pan neuronal marker PGP9.5. Three-dimensional confocal pictures of the upper and lower human airways were analysed regarding the mast cell-nerve colocalisation and mast cell degranulation. To set up an acute allergic phase, human precision cut lung slices (PCLS) were passively sensitized with plasma from allergic patients. Subsequently, bronchoconstriction was provoked with the allergen house dust mite (HDM) or with capsaicin +/- histamine 1 receptor antagonist. Bronchoconstriction was visualized by videomicroscopy analyzing airway area reduction in PCLS.  Close mast cell-nerve interactions were shown in the airways of three human donors. Capsaicin-treated passive sensitized PCLS showed mast cell degranulation using primary antibodies against mast cell tryptase, bound IgE and the neuropeptide substance P. HDM and capsaicin- induced bronchoconstriction showed reduction of the airway area in 30 % and 40 % respectively. Capsaicin- induced AHR was totally inhibited by 10 µM of the histamine 1 receptor antagonist., showing that mast cells and histamine release is involved in capsaicin-induced bronchoconstriction.  Here we show the importance of neuroimmunologic features involved in respiratory diseases such as asthma.
Rapid-Learning System for Cancer Care
Authors: Amy P. Abernethy, Lynn M. Etheredge, Patricia A. Ganz, Paul Wallace, Robert R. German, Chalapathy Neti, Peter B. Bach, Sharon B. Murphy
Journal: Journal of Clinical Oncology (2010)

Compelling public interest is propelling national efforts to advance the evidence base for cancer treatment and control measures and to transform the way in which evidence is aggregated and applied. Substantial investments in health information technology, comparative effectiveness research, health care quality and value, and personalized medicine support these efforts and have resulted in considerable progress to date. An emerging initiative, and one that integrates these converging approaches to improving health care, is "rapid-learning health care." In this framework, routinely collected real-time clinical data drive the process of scientific discovery, which becomes a natural outgrowth of patient care. To better understand the state of the rapid-learning health care model and its potential implications for oncology, the National Cancer Policy Forum of the Institute of Medicine held a workshop entitled "A Foundation for Evidence-Driven Practice: A Rapid-Learning System for Cancer Care" in October 2009. Participants examined the elements of a rapid-learning system for cancer, including registries and databases, emerging information technology, patient-centered and -driven clinical decision support, patient engagement, culture change, clinical practice guidelines, point-of-care needs in clinical oncology, and federal policy issues and implications. This Special Article reviews the activities of the workshop and sets the stage to move from vision to action.
The role of positron emission tomography (PET) in the management of lymphoma patients
Authors: P.L. Zinzani, M. Magagnoli, F. Chierichetti, M. Zompatori, G. Garraffa, M. Bendandi, F. Gherlinzoni, C. Cellini, V. Stefoni, G. Ferlin, S. Tura
Journal: Annals of Oncology (1999)
The Number of Alleles at a Microsatellite Defines the Allele Frequency Spectrum and Facilitates Fast Accurate Estimation of 
Authors: R. J. Haasl, B. A. Payseur
Journal: Molecular Biology and Evolution (2010)

Theoretical work focused on microsatellite variation has produced a number of important results, including the expected distribution of repeat sizes and the expected squared difference in repeat size between two randomly selected samples. However, closed-form expressions for the sampling distribution and frequency spectrum of microsatellite variation have not been identified. Here, we use coalescent simulations of the stepwise mutation model to develop gamma and exponential approximations of the microsatellite allele frequency spectrum, a distribution central to the description of microsatellite variation across the genome. For both approximations, the parameter of biological relevance is the number of alleles at a locus, which we express as a function of θ, the population-scaled mutation rate, based on simulated data. Discovered relationships between θ, the number of alleles, and the frequency spectrum support the development of three new estimators of microsatellite θ. The three estimators exhibit roughly similar mean squared errors (MSEs) and all are biased. However, across a broad range of sample sizes and θ values, the MSEs of these estimators are frequently lower than all other estimators tested. The new estimators are also reasonably robust to mutation that includes step sizes greater than one. Finally, our approximation to the microsatellite allele frequency spectrum provides a null distribution of microsatellite variation. In this context, a preliminary analysis of the effects of demographic change on the frequency spectrum is performed. We suggest that simulations of the microsatellite frequency spectrum under evolutionary scenarios of interest may guide investigators to the use of relevant and sometimes novel summary statistics.
In Vitro Myelosuppression and Immunosuppression by Ethanol
Authors: Glenn Tisman, Victor Herbert
Journal: Journal of Clinical Investigation (1973)

Concentrations of ethanol similar to those in the blood of intoxicated patients suppressed phytohemagglutinin- or streptolysin O-induced lymphocyte transformation, and inhibited bone marrow granulocyte colony growth in soft agar. Inhibition of lymphocyte transformation and granulocyte colony growth occurred despite the presence of large concentrations of folate and other vitamins. These in vitro findings may relate to in vivo effects of ethanol on myeloid and lymphoid tissue.
Physiologic and Anatomic Effects of Propylthiouracil on Normal and Hypertensive Rats
Authors: M. J. FREGLY, C. I. HOOD
Journal: Circulation Research (1959)

The antithyroid drug propylthiouracil prevented or removed the hypertension associated with bilateral kidney encapsulation with latex envelopes. This effect did not appear to be the result of hypofunction of the adrenal glands. Propylthiouracil reduced growth rate in young rats and caused weight loss in adult rats. The latter effect appeared to be true tissue loss because water contents of heart, kidney, testes, liver, psoas, aorta and adrenal were unaffected. Administration of propylthiouracil for 7 to 19 weeks tended to reduce heart weight to body weight ratio as well as the ratio of kidney weight to body weight in both control and "encapsulated" rats. However, ratios of organ weight to body weight in the cases of thyroid, testes and eyes were larger than those of untreated control rats. In addition to its antihypertensive effect, propylthiouracil treatment of encapsulated rats also prevented the appearance of certain other manifestations of hypertension usually accompanying kidney encapsulation.
The longitudinal relationship between changes in body weight and changes in medial tibial cartilage, and pain among community-based adults with and without meniscal tears
Authors: Andrew J Teichtahl, Anita E Wluka, Yuanyuan Wang, Boyd J Strauss, Joseph Proietto, John B Dixon, Graeme Jones, Andrew Forbes, Susan Kouloyan-Ilic, Johanne Martel-Pelletier, Jean-Pierre Pelletier, Flavia M Cicuttini
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Introduction</h3> Meniscal tears are commonly found on MRI and increase the risk for radiographic knee osteoarthritis (OA). While meniscectomy is recommended when knee pain is severe or functionally disabling, it is unclear how to best treat meniscal tears without these symptoms. The aim of this longitudinal study was to examine the effect of weight change on knee cartilage and pain in a cohort of community-based adults with and without meniscal tears detected by MRI. <h3>Methods</h3> 250 adults with no history of knee OA or knee injury were recruited from the general community and weight-loss clinics. MRI of the knee, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), weight and height were measured at baseline and again at follow-up approximately 2 years later. <h3>Results</h3> Medial meniscal tears were present in 36 (18%) of the cohort. In those with medial meniscal tears, after adjustment for confounders, percentage weight change was significantly associated with percentage change in medial tibial cartilage volume (β 0.2% 95% CI 0.08% to 0.3% p=0.002) and knee pain (β 11.6% 95% CI 2.1% to 21.1% p=0.02). That is, for every 1% gain in weight, there was an associated 0.2% increased loss of medial tibial cartilage volume and 11.6% increase in pain. In those with no medial meniscal tear, neither change in medial tibial cartilage volume (β 0.02% 95% CI −0.01% to 0.10% p=0.53) or pain (β 1.9% 95% CI −2.2% to 6.1% p=0.36) were significantly associated with change in weight. <h3>Conclusions</h3> This study demonstrated that among adults with medial meniscal tears, weight gain is associated with increased cartilage loss and pain, while weight loss is associated with the converse. This suggests attention to weight is particularly important in the management of people with medial meniscal tears.
STUDIES WITH THE ELECTRON MICROSCOPE OF VIRUS-HOST RELATIONSHIPS IN EHRLICH ASCITES TUMOR CELLS
Authors: Marlene Friedlaender, Dan H. Moore, Robert Love, Ray A. Brown, Hilary Koprowski
Journal: The Journal of Experimental Medicine (1955)

Sections of Ehrlich ascites tumor cells infected with anopheles A virus revealed particles in the cytoplasm, which were identified as the virus on the basis of their consistent size and internal structure; their high opacity in the electron beam after fixation with osmic acid; the localized occurrence, within a certain time interval following infection, of high concentrations of such particles within the cell; the absence of similar particles in uninoculated tumor cells and cells infected with other viruses, and the appearance of such particles in infected chorioallantoic membrane. The particles are spheroid, with a transparent 25 to 30 mµ core, surrounded by an opaque complex shell 12 to 17 mµ in thickness. Apparently "hollow," globular components of this shell have outer and inner diameters of approximately 12 mµ and 5 to 7 mµ respectively. The validity of an additional outer envelope is discussed. Particles are frequently embedded in a matrix, and their alignment and grouping are discussed. Markedly dense populations are found near nuclear concavities. Some infective changes in the cell are described, for example the formation of newly observed virus-induced necrotic regions.
Selective CD4<sup>+</sup> Lymphopenia in Melanoma Patients Treated With Temozolomide: A Toxicity With Therapeutic Implications
Authors: Y.B. Su, Sejean Sohn, Susan E. Krown, Philip O. Livingston, Jedd D. Wolchok, Carolyn Quinn, Linda Williams, Theresa Foster, Kent A. Sepkowitz, Paul B. Chapman
Journal: Journal of Clinical Oncology (2004)

Purpose Standard schedule temozolomide (TMZ; daily for 5 days every 4 weeks) is often used in melanoma patients, but phase III data show that it is no more effective than standard dacarbazine. Extended TMZ dosing regimens may be superior by delivering the drug continuously at a higher dose over time. Using an extended dosing schedule, we noted a high incidence of lymphopenia and occasional opportunistic infections (OIs). Here we report our retrospective experience in the first 97 patients. Materials and Methods TMZ was administered at 75 mg/m 2 /d orally for 6 weeks every 8 weeks, although nine patients were treated continuously without a break. Seventeen patients were treated with TMZ alone; 73 patients received TMZ with thalidomide; seven patients received TMZ with low-dose interferon alfa. Results Median duration of TMZ treatment was 113 days; 29% received ≥ 24 weeks of therapy. Lymphopenia was seen in 60% of patients (absolute lymphocyte count &lt; 800/μL) with a median of 101 days to lymphopenia. TMZ did not cause significant neutropenia or thrombocytopenia. Lymphopenia was not more common in patients treated concomitantly with thalidomide. In all patients analyzed for lymphocyte subsets, lymphopenia induced by TMZ affected the CD4 + compartment preferentially. There were two documented OIs (Pneumocystis and Aspergillus pneumonia) as well as other infections indicative of T-cell dysfunction in another 21 patients. Conclusion TMZ at this dose and schedule results in CD4 + lymphopenia in a majority of patients that can result in OIs. Pneumocystis pneumonia prophylaxis should be considered for patients who develop sustained lymphopenia on TMZ.
A Genomic Strategy to Refine Prognosis in Early-Stage Non–Small-Cell Lung Cancer
Authors: Anil Potti, Sayan Mukherjee, Rebecca Petersen, Holly K. Dressman, Andrea Bild, Jason Koontz, Robert Kratzke, Mark A. Watson, Michael Kelley, Geoffrey S. Ginsburg, Mike West, David H. Harpole, Joseph R. Nevins
Journal: New England Journal of Medicine (2006)

Clinical trials have indicated a benefit of adjuvant chemotherapy for patients with stage IB, II, or IIIA--but not stage IA--non-small-cell lung cancer (NSCLC). This classification scheme is probably an imprecise predictor of the prognosis of an individual patient. Indeed, approximately 25 percent of patients with stage IA disease have a recurrence after surgery, suggesting the need to identify patients in this subgroup for more effective therapy.We identified gene-expression profiles that predicted the risk of recurrence in a cohort of 89 patients with early-stage NSCLC (the lung metagene model). We evaluated the predictor in two independent groups of 25 patients from the American College of Surgeons Oncology Group (ACOSOG) Z0030 study and 84 patients from the Cancer and Leukemia Group B (CALGB) 9761 study.The lung metagene model predicted recurrence for individual patients significantly better than did clinical prognostic factors and was consistent across all early stages of NSCLC. Applied to the cohorts from the ACOSOG Z0030 trial and the CALGB 9761 trial, the lung metagene model had an overall predictive accuracy of 72 percent and 79 percent, respectively. The predictor also identified a subgroup of patients with stage IA disease who were at high risk for recurrence and who might be best treated by adjuvant chemotherapy.The lung metagene model provides a potential mechanism to refine the estimation of a patient's risk of disease recurrence and, in principle, to alter decisions regarding the use of adjuvant chemotherapy in early-stage NSCLC.
Occult hepatitis B virus infection in patients with non-Hodgkin lymphoma: the need for early diagnosis in anti-Hbc positive patients
Authors: E Persico, A De Renzo, V La Mura, S Bruno, M Masarone, R Torella, M Persico
Journal: Gut (2007)

Occult hepatitis B virus infection in patients with non-Hodgkin lymphoma: the need for early diagnosis in anti-Hbc positive patients
Analysis of Promoter CpG Island Hypermethylation in Cancer: Location, Location, Location!
Authors: Iris J.H. van Vlodrop, Hanneke E.C. Niessen, Sarah Derks, Marcella M.L.L. Baldewijns, Wim van Criekinge, James G. Herman, Manon van Engeland
Journal: Clinical Cancer Research (2011)

Abstract The genetic and epigenetic alterations that underlie cancer pathogenesis are rapidly being identified. This provides novel insights in tumor biology as well as in potential cancer biomarkers. The somatic mutations in cancer genes that have been implemented in clinical practice are well defined and very specific. For epigenetic alterations, and more specifically aberrant methylation of promoter CpG islands, evidence is emerging that these markers could be used for the early detection of cancer as well as prediction of prognosis and response to therapy. However, the exact location of biologically and clinically relevant hypermethylation has not been identified for the majority of methylation markers. The most widely used approaches to analyze DNA methylation are based on primer- and probe-based assays that provide information for a limited number of CpG dinucleotides and thus for only part of the information available in a given CpG island. Validation of the current data and implementation of hypermethylation markers in clinical practice require a more comprehensive and critical evaluation of DNA methylation and limitations of the techniques currently used in methylation marker research. Here, we discuss the emerging evidence on the importance of the location of CpG dinucleotide hypermethylation in relation to gene expression and associations with clinicopathologic characteristics in cancer. Clin Cancer Res; 17(13); 4225–31. ©2011 AACR.
Linear Ablation of the Isthmus Between the Inferior Vena Cava and Tricuspid Annulus for the Treatment of Atrial Flutter
Authors: Toshifumi Tabuchi, Ken Okumura, Toshiro Matsunaga, Ryusuke Tsunoda, Michihisa Jougasaki, Hirofumi Yasue
Journal: Circulation (1995)

The isthmus between the inferior vena cava and the tricuspid annulus has been shown to be involved in the reentry circuit of common atrial flutter. The effects of radio-frequency catheter ablation of this isthmus were examined in the canine model of atrial flutter due to reentry around the tricuspid annulus.A model of atrial flutter was prepared in 11 of 14 dogs by creating intercaval and connected transverse lesions (Y-shaped lesion). Bipolar electrodes were attached at 24 atrial sites, and computer-assisted mapping was performed. Stable atrial flutter with a cycle length of 133 +/- 11 ms was repeatedly induced by rapid atrial pacing in all dogs, and atrial mapping revealed reentry around the tricuspid annulus including the isthmus. In 6 dogs, the isthmus was ligated during atrial flutter (mechanical ablation). In the other 5 dogs, a 7F large-tip electrode catheter was placed at the isthmus under a fluoroscopic control. Radiofrequency energy (25 W for 30 s) was delivered to three sequential sites from the tricuspid annulus to the inferior vena cava to ablate the isthmus linearly. Atrial flutter was terminated in all dogs after mechanical and radio-frequency ablation of the isthmus and was not induced again. Atrial pacing from the posterior left atrium during sinus rhythm demonstrated intra-atrial conduction block at the isthmus after ablation. Pathological examination of the isthmus showed transmural myocardial damage.Linear radiofrequency ablation of the isthmus can induce intra-atrial conduction block and is effective as a curative therapy for atrial flutter when the reentry circuit involves the isthmus.
THE USE OF NEUTRACEUTICALS IN SPORTS AND EXERCISE MEDICINE
Authors: David Johnson, S Johnson-Verma
Journal: British Journal of Sports Medicine (2013)

Introduction Athletes and weekend warriors alike periodically suffer from musculoskeletal injuries resulting in loss of training time and in some cases, missed competitions. Even everyday training produces micro-trauma and has its own recovery demands. Methodology Review paper. This presentation will focus on evidence-based usage of particular nutrients on the various phases of the soft tissue injury healing process. Discussion There is evidence to suggest the successful use of particular nutraceuticals aiding the athletes' recovery. Examples include omega-3 oils, Curcumin, vitamin-d, methylsulfonyl methane (MSM), Glucosamine Sulfate, Chondroitin Sulfate and proteolytic enzymes. Conclusion This review and its findings can be incorporated into everyday sports and exercise medicine practice.
β-Arrestin–mediated β1-adrenergic receptor transactivation of the EGFR confers cardioprotection
Authors: Takahisa Noma, Anthony Lemaire, Sathyamangla V. Naga Prasad, Liza Barki-Harrington, Douglas G. Tilley, Juhsien Chen, Philippe Le Corvoisier, Jonathan D. Violin, Huijun Wei, Robert J. Lefkowitz, Howard A. Rockman
Journal: Journal of Clinical Investigation (2007)

Deleterious effects on the heart from chronic stimulation of β-adrenergic receptors (βARs), members of the 7 transmembrane receptor family, have classically been shown to result from Gs-dependent adenylyl cyclase activation. Here, we identify a new signaling mechanism using both in vitro and in vivo systems whereby β-arrestins mediate β1AR signaling to the EGFR. This β-arrestin–dependent transactivation of the EGFR, which is independent of G protein activation, requires the G protein–coupled receptor kinases 5 and 6. In mice undergoing chronic sympathetic stimulation, this novel signaling pathway is shown to promote activation of cardioprotective pathways that counteract the effects of catecholamine toxicity. These findings suggest that drugs that act as classical antagonists for G protein signaling, but also stimulate signaling via β-arrestin–mediated cytoprotective pathways, would represent a novel class of agents that could be developed for multiple members of the 7 transmembrane receptor family.
Polymorphism in cytokine genes as prognostic markers in Hodgkin's lymphoma
Authors: S Hohaus, M Giachelia, A Di Febo, M Martini, G Massini, B Vannata, F D'Alo', F Guidi, M Greco, F Pierconti, L.M. Larocca, M.T. Voso, G Leone
Journal: Annals of Oncology (2007)