tbuckley/cabot-search huggingface dataset:
Proinflammatory mediators elicit secretion of the intracellular B-lymphocyte stimulator pool (BLyS) that is stored in activated neutrophils: implications for inflammatory diseases
Authors: Patrizia Scapini, Antonio Carletto, Bernardetta Nardelli, Federica Calzetti, Viktor Roschke, Flavia Merigo, Nicola Tamassia, Sara Pieropan, Domenico Biasi, Andrea Sbarbati, Silvano Sozzani, Lisa Bambara, Marco A. Cassatella
Journal: Blood (2004)
Electromyographic analysis of knee push up plus variations: what is the influence of the kinetic chain on scapular muscle activity?
Authors: A Maenhout, K Van Praet, L Pizzi, M Van Herzeele, A Cools
Journal: British Journal of Sports Medicine (2009)

Objective First, to look for appropriate closed kinetic chain exercises to restore intramuscular imbalance between upper trapezius (UT) and serratus anterior (SA) in overhead athletes. Second, to determine the influence of using diagonal pattern muscle recruitment during knee push up plus (KPP) exercises on scapular electromyographic activity. Design Single group repeated-measures design. Setting Controlled laboratory study. Participants Thirty-two physically active individuals in good general health who did not have a history of neck and/or shoulder injury or surgery nor participated in high-level overhead sports or performed upper limb strength training for more than 5 h/week. Interventions Subjects performed the standard KPP and six variations. Main outcome measurements Electromyographic activity of the three trapezius parts and the SA. Results Four exercises with a low UT/SA can be selected for rehabilitation of intramuscular balance: standard KPP, KPP with homolateral leg extension, KPP with a wobble board and homolateral leg extension and one-handed KPP. The use of a wobble board during KPP exercises and performance on one hand has no influence on SA electromyographic activity. Heterolateral leg extension during KPP stimulates lower trapezius activity, whereas homolateral leg extension stimulates SA activity. Conclusions In case of intramuscular scapular imbalance, some exercises are preferable over others because of their low UT/SA ratio. The use of a kinetic chain approach during KPP exercises influences scapular muscle activity.
Continuity – our Achilles' heel
Authors: Gareth E Vincenti
Journal: Journal of the Royal Society of Medicine (2010)

The CMO and his co-authors rightly deplore the lack of meaningful progress in reducing healthcare error.1 However, the answer may be close at hand. In their informative editorial, they describe ‘Toyota's LEAN methodology’ as ‘increasingly popular in identifying inefficiency and improving performance’. It is difficult to see what benefit might accrue to healthcare in this country from following the principles of a company that is at the centre of a worldwide product safety recall of literally millions of its motor vehicles, and whose profits have plummeted through the floor in the past year. Perhaps it would now be appropriate to call time on our reliance upon inappropriate business models when looking to improve healthcare performance in both the NHS and private sectors.
Loss of <i>Xeroderma Pigmentosum C</i> (<i>Xpc</i>) Enhances Melanoma Photocarcinogenesis in <i>Ink4a-Arf</i>–Deficient Mice
Authors: Guang Yang, David Curley, Marcus W. Bosenberg, Hensin Tsao
Journal: Cancer Research (2007)

Abstract Despite an extensive body of evidence linking UV radiation and melanoma tumorigenesis, a clear mechanistic understanding of this process is still lacking. Because heritable mutations in both INK4a and the nucleotide excision repair (NER) pathway predispose individuals to melanoma development, we set out to test the hypothesis that abrogation of NER, by deletion of the xeroderma pigmentosum C (Xpc) gene, will heighten melanoma photocarcinogenesis in an Ink4a-Arf–deficient background. Experimentally, we generated a strain of mice doubly deficient in Xpc and Ink4a-Arf and subjected wild-type, Xpc−/−Ink4a-Arf+/+, Xpc−/−Ink4a-Arf−/−, and Xpc+/+Ink4a-Arf−/− mice to a single neonatal (day P3) dose of UVB without additional chemical promotion. Indeed, there was a significant increase in the development of dermal spindle/epithelioid cell melanomas in Xpc−/−Ink4a-Arf−/− mice when compared with Xpc+/+Ink4a-Arf−/− mice (P = 0.005); wild-type and Xpc−/−Ink4a-Arf+/+ mice failed to develop tumors. These neoplasms bore a striking histologic resemblance to melanomas that arise in the Tyr-vHRAS/Ink4a-Arf−/− context and often expressed melanocyte differentiation marker Tyrp1, thus supporting their melanocytic origination. All strains, except wild-type mice, developed pigmented and non-pigmented epidermal-derived keratinocytic cysts, whereas Xpc+/+Ink4a-Arf−/− mice exhibited the greatest propensity for squamous cell carcinoma development. We then screened for NRas, HRas, Kras, and BRaf mutations in tumor tissue and detected a higher frequency of rare KrasQ61 alterations in tumors from Xpc−/−Ink4a-Arf−/− mice compared with Xpc+/+Ink4a-Arf−/− mice (50% versus 7%, P = 0.033). Taken together, results from this novel UV-inducible melanoma model suggest that NER loss, in conjunction with Ink4a-Arf inactivation, can drive melanoma photocarcinogenesis possibly through signature Kras mutagenesis. [Cancer Res 2007;67(12):5649–57]
AMP-Activated Protein Kinase Regulates E3 Ligases in Rodent Heart
Authors: Kedryn K. Baskin, Heinrich Taegtmeyer
Journal: Circulation Research (2011)

Rationale: The degradation of proteins by the ubiquitin proteasome system (UPS) is required for the maintenance of cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). AMPK activation inhibits protein synthesis and activates autophagy, but whether AMPK plays a role in regulating protein breakdown through the UPS in the heart is not known. Objective: To determine whether AMPK enhances UPS-mediated protein degradation by directly regulating the ubiquitin ligases Atrogin-1 and muscle RING finger protein 1 (MuRF1) in the heart. Methods and Results: Nutrient deprivation and pharmacological or genetic activation of AMPK increased mRNA expression and protein levels of Atrogin-1 and MuRF1 and consequently enhanced protein degradation in neonatal cardiomyocytes. Inhibition of AMPK abrogated these effects. Using gene reporter and chromatin immunoprecipitation assays, we found that AMPK regulates MuRF1 expression by acting through the myocyte enhancer factor 2 (MEF2). We further validated these findings in vivo using MEF2-LacZ reporter mice. Furthermore, we demonstrated in adult cardiomyocytes that MuRF1 is necessary for AMPK-mediated proteolysis through the UPS in the heart. Consequently, MuRF1 knockout mice were protected from severe cardiac dysfunction during fasting. Conclusions: AMPK regulates the transcription of Atrogin-1 and MuRF1 and enhances UPS-mediated protein degradation in heart. Specifically, AMPK regulates MuRF1 through the transcription factor MEF2. The absence of MuRF1 in the heart preserves cardiac function during fasting. The results strengthen the hypothesis that AMPK serves as a modulator of intracellular protein degradation in the heart.
Pre-B-cell leukemia homeobox interacting protein 1 is overexpressed in astrocytoma and promotes tumor cell growth and migration
Authors: Dannis G. van Vuurden, Eleonora Aronica, Esther Hulleman, Laurine E. Wedekind, Dennis Biesmans, Arjan Malekzadeh, Marianna Bugiani, Dirk Geerts, David P. Noske, W. Peter Vandertop, Gertjan J.L. Kaspers, Jacqueline Cloos, Thomas Würdinger, Petra P.M. van der Stoop
Journal: Neuro-Oncology (2014)

Glial brain tumors cause considerable mortality and morbidity in children and adults. Innovative targets for therapy are needed to improve survival and reduce long-term sequelae. The aim of this study was to find a candidate tumor-promoting protein, abundantly expressed in tumor cells but not in normal brain tissues, as a potential target for therapy. In silico proteomics and genomics, immunohistochemistry, and immunofluorescence microscopy validation were performed. RNA interference was used to ascertain the functional role of the overexpressed candidate target protein. In silico proteomics and genomics revealed pre-B-cell leukemia homeobox (PBX) interacting protein 1 (PBXIP1) overexpression in adult and childhood high-grade glioma and ependymoma compared with normal brain. PBXIP1 is a PBX-family interacting microtubule-binding protein with a putative role in migration and proliferation of cancer cells. Immunohistochemical studies in glial tumors validated PBXIP1 expression in astrocytoma and ependymoma but not in oligodendroglioma. RNAi-mediated PBXIP1-knockdown in glioblastoma cell lines strongly reduced proliferation and migration and induced morphological changes, indicating that PBXIP1 knockdown decreases glioma cell viability and motility through rearrangements of the actin cytoskeleton. Furthermore, expression of PBXIP1 was observed in radial glia and astrocytic progenitor cells in human fetal tissues, suggesting that PBXIP1 is an astroglial progenitor cell marker during human embryonic development. PBXIP1 is a novel protein overexpressed in astrocytoma and ependymoma, involved in tumor cell proliferation and migration, that warrants further exploration as a novel therapeutic target in these tumors.
Pneumonia in low and middle income countries: progress and challenges
Authors: H J Zar, S A Madhi, S J Aston, S B Gordon
Journal: Thorax (2013)

Pneumonia remains the leading cause of childhood mortality and the most common reason for adult hospitalisation in low and middle income countries, despite advances in preventative and management strategies. In the last decade, pneumonia mortality in children has fallen to approximately 1.3 million cases in 2011, with most deaths occurring in low income countries. Important recent advances include more widespread implementation of protein-polysaccharide conjugate vaccines against <i>Haemophilus influenzae type B</i> and <i>Streptococcus pneumoniae</i>, implementation of case-management algorithms and better prevention and treatment of HIV. Determining the aetiology of pneumonia is challenging in the absence of reliable diagnostic tests. High uptake of new bacterial conjugate vaccines may impact on pneumonia burden, aetiology and empiric therapy but implementation in immunisation programmes in many low and middle income countries remains an obstacle. Widespread implementation of currently effective preventative and management strategies for pneumonia remains challenging in many low and middle income countries.
Airway Epithelial Changes in Smokers but Not in Ex-Smokers with Asthma
Authors: Martine Broekema, Nick H. T. ten Hacken, Franke Volbeda, Monique E. Lodewijk, Machteld N. Hylkema, Dirkje S. Postma, Wim Timens
Journal: American Journal of Respiratory and Critical Care Medicine (2009)

Smoking has detrimental effects on asthma outcome, such as increased cough, wheezing, sputum production, and frequency of asthma attacks. This results in accelerated lung function decline. The underlying pathological process of smoke-induced deterioration of asthma is unknown.To compare bronchial inflammation and remodeling in never-smokers, ex-smokers, and current smokers with asthma.A total of 147 patients with asthma (66 never-smokers, 46 ex-smokers, and 35 current smokers) were investigated.Lung function, exhaled nitric oxide levels, and symptom questionnaires were assessed, and induced sputum and bronchial biopsies were obtained for determination of airway inflammation and remodeling. Smokers with asthma had lower FEV(1) and alveolar and bronchial nitric oxide levels than never-smokers. Smokers also had more goblet cells and mucus-positive epithelium, increased epithelial thickness, and a higher proliferation rate of intact and basal epithelium than ex-smokers and never-smokers. Smokers had higher numbers of mast cells and lower numbers of eosinophils than never-smokers. Ex-smokers had similar goblet cell numbers and mucus-positive epithelium, epithelial thickness, epithelial proliferation rate, and mast cell numbers as never-smokers.Smokers with asthma have epithelial changes that are associated with increased asthma symptoms, such as shortness of breath and phlegm production. The fact that epithelial characteristics in ex-smokers are similar to those in never-smokers suggests that the smoke-induced changes can be reversed by smoking cessation.
Beyond Advance Directives
Authors: James A. Tulsky
Journal: JAMA (2005)

Patients and their families struggle with myriad choices concerning medical treatments that frequently precede death. Advance directives have been proposed as a tool to facilitate end-of-life decision making, yet frequently fail to achieve this goal. In the context of the case of a man with metastatic cancer for whom an advance directive was unable to prevent a traumatic death, I review the challenges in creating and implementing advance directives, discuss factors that can affect clear decision making; including trust, uncertainty, emotion, hope, and the presence of multiple medical providers; and offer practical suggestions for physicians. Advance care planning remains a useful tool for approaching conversations with patients about the end of life. However, such planning should occur within a framework that emphasizes responding to patient and family emotions and focuses more on goals for care and less on specific treatments.
β-Catenin Is Dispensable for Hematopoiesis and Lymphopoiesis
Authors: Monica Cobas, Anne Wilson, Bettina Ernst, Stéphane J.C. Mancini, H. Robson MacDonald, Rolf Kemler, Freddy Radtke
Journal: The Journal of Experimental Medicine (2004)

β-catenin–mediated Wnt signaling has been suggested to be critically involved in hematopoietic stem cell maintenance and development of T and B cells in the immune system. Unexpectedly, here we report that inducible Cre-loxP–mediated inactivation of the β-catenin gene in bone marrow progenitors does not impair their ability to self-renew and reconstitute all hematopoietic lineages (myeloid, erythroid, and lymphoid), even in competitive mixed chimeras. In addition, both thymocyte survival and antigen-induced proliferation of peripheral T cells is β-catenin independent. In contrast to earlier reports, these data exclude an essential role for β-catenin during hematopoiesis and lymphopoiesis.
Relation Between Blood Flow and Contraction Force in Active Skeletal Muscle
Authors: Leo Hirvonen, Ralph R. Sonnenschein
Journal: Circulation Research (1962)

The relationships between blood flow and contraction force in intermittently contracting eat skeletal muscle during alterations of flow by various procedures were studied. When flow only to the active gastrocuemiussoleus was measured, mechanical reduction in perfusion pressure, sympathetic chain stimulation and intra-arterial norepinephrine and epinephrine infusion were found to have esscritially identical effects in producing reduction in muscle force proportionate to that in blood flow. When flow in the whole leg musculature was measured while either the gastrocnemius-soleus or the quadriceps was active, varying results were obtained with these procedures which could be ascribed to differenees in response of vessels in active and resting muscles. During the carotid sinus reflex some vasoconstrictor activity occurred in active muscle. On the assumption that the maximal, muscle force is an index of the nutritional component of the flow, it may be inferred that, in general, those procedures in which total flow was restricted produced no alteration in distribution of nutritional and non-nutritional flow within the active muscle. Blood flow and muscle force were generally unaffected by concomitant stimulation in the hypothalamus of the sympathetic vasodilator system. An increase in flow and force occasionally was observed whien these were at low levels, or when a rise in arterial pressure occurred. The sympathetic vasodilator system produces no alteration in distibution of flow and would seem to play no role in the maintenance of blood flow and performance of normal active muscle. A fundamental difference appears to exist in the responses of the vasculature of resting and active skeletal muscle; this difference is related to the interplay of specialized effects of the vasomotor innervations and the action of vasodilator metabolites.
Suppression of leukocyte chemotaxis by human IgA myeloma components.
Authors: D E Van Epps, R C Williams
Journal: The Journal of Experimental Medicine (1976)

Sera from patients with IgA myeloma suppressed polymorphonuclear leukocyte (PMN) chemotaxis, while generally little or no suppression was observed with sera from patients with IgG myeloma or Waldenstrom's macroglobulinemia. Chemotactic inhibitory activity was not limited to a single chemotactic factor and was equivalent when C5a, bacterial factor, casein, or normal serum were used as chemotactic attractants. No association was noted between the degree of inhibitory activity and the IgA subclass or light chain type. Chemotactic inhibitory activity was found to be directly associated with isolated IgA M components, and similar chemotactic suppression was noted with purified preparations of normal human colostral IgA. By comparison, IgA preparations were most effective in suppressing PMN chemotaxis and had a much lesser effect on monocyte chemotaxis. The mode of IgA chemotactic inhibition was cellular and at least partially reversible after a 37degreesC incubation in the absence of IgA. Some inhibition of PMN random mobility was noted with certain IgA preparations, although such effects did not parallel the degree of chemotactic inhibition. Fractionation of IgA myeloma sera and IgA M components by sucrose density gradient centrifugation showed multiple peaks of inhibitory activity in 10 to 13S fractions. The majority of IgA inhibitory activity was lost after pepsin digestion or sulfhydryl reduction and alkylation of isolated M components. When isolated IgA M components were fractionated on Sephadex G-200, inhibitory activity was associated with the exclusion volume and was abolished by reduction and alkylation procedures which resulted in a conversion of polymeric IgA to monomeric IgA.
Patterns of Treatment Failure in Pediatric and Young Adult Patients With Hodgkin's Disease: Local Disease Control With Combined-Modality Therapy
Authors: Matthew J. Krasin, Shesh N. Rai, Larry E. Kun, Thomas E. Merchant, Monika L. Metzger, Sue C. Kaste, Scott C. Howard, Melissa M. Hudson
Journal: Journal of Clinical Oncology (2005)

Purpose Refinement in managing pediatric Hodgkin's disease (HD) requires understanding of factors associated with local treatment failure. This study defines the cumulative incidence (CI) of local failure (LF) and prognostic factors for pediatric patients treated for HD with combined-modality therapy (CMT). Patients and Methods We enrolled 195 patients onto two prospective studies at St Jude Children's Research Hospital between 1990 and 2000. Patients received CMT with chemotherapy (vinblastine, doxorubicin, methotrexate, and prednisone [VAMP]; vinblastine, etoposide, prednisone, and doxorubicin; or VAMP/cyclophosphamide, vincristine, and procarbazine) and involved-field radiation therapy delivered to initial site(s) of disease on the basis of early response. Sites of disease involvement, treatment, and sites of failure were confirmed from the patients' medical record, imaging, and radiotherapy treatment records. We estimated the overall survival, event-free survival, and CI of LF. Results With a median follow-up of 7.6 years, the CI of LF was 10.9% and 11.6% at 5 and 10 years, respectively. Twenty-seven (14%) of 195 patients experienced recurrence of HD, and 22 (81%) of those experienced LF. Bulky mediastinal disease greater than one third transthoracic diameter predicted a higher incidence of LF, but did not predict failure in the mediastinum. Male sex, low initial hemoglobin, and bulky mediastinal disease were prognostic indicators of LF. Attenuation of radiation dose to 15 Gy based on response provides excellent infield control. Conclusion CMT provides excellent local disease control in children and young adults with HD. LF remains a primary site of disease recurrence, with male sex, low initial hemoglobin, and bulky mediastinal disease predicting for LF.
Age-Specific Associations between Cardiac Vagal Activity and Functional Somatic Symptoms: A Population-Based Study
Authors: Lineke M. Tak, Karin A.M. Janssens, Andrea Dietrich, Joris P.J. Slaets, Judith G.M. Rosmalen
Journal: Psychotherapy and Psychosomatics (2010)

&lt;i&gt;Background:&lt;/i&gt; Functional somatic symptoms (FSS) are symptoms not explained by underlying organic pathology. It has frequently been suggested that dysfunction of the autonomic nervous system (ANS) contributes to the development of FSS. We hypothesized that decreased cardiac vagal activity is cross-sectionally and prospectively associated with the number of FSS in the general population. &lt;i&gt;Methods:&lt;/i&gt; This study was performed in a population-based cohort of 774 adults (45.1% male, mean age ± SD 53.5 ± 10.7 years). Participants completed the somatization section of the Composite International Diagnostic Interview surveying the presence of 43 FSS. ANS function was assessed by spectral analysis of heart rate variability in the high-frequency band (HRV-HF), reflecting cardiac vagal activity. Follow-up measurements of HRV-HF and FSS were performed approximately 2 years later. &lt;i&gt;Results:&lt;/i&gt; Linear regression analyses, with adjustments for gender, age, body mass index, anxiety, depression, smoking, alcohol use, and frequency of exercise, revealed an interaction of cardiac vagal activity with age: HRV-HF was negatively associated with FSS in adults ≤52 years of age (β = –0.12, t = –2.37, p = 0.018), but positively with FSS in adults aged &gt;52 years (β = 0.13, t = 2.51, p = 0.012). Longitudinal analysis demonstrated a similar pattern. &lt;i&gt;Conclusions:&lt;/i&gt; Decreased cardiac vagal activity is associated with a higher number of FSS in adults aged ≤52 years in the general population. The unexpected association between increased cardiac vagal activity and FSS in adults aged &gt;52 years needs further exploration. The role of age should be acknowledged in future studies on ANS function in the etiology of FSS.
Evidence-based prevention of post-operative adhesions
Authors: A. Johns
Journal: Human Reproduction Update (2001)

Despite decades of research, numerous new product ideas and 'carefully considered opinions' of recognized experts, very few products for the prevention of post-operative adhesions have met the requirements for Level 1 evidence of safety and efficacy. Those that have are useable only at laparotomy. Several new liquid products intended for use at laparoscopy are in various stages of development and clinical investigation. Hopefully, some will prove to be both simple to use and efficacious. Even if this occurs, it must be remembered that a reduction in post-operative adhesions does not necessarily produce a better clinical outcome. Our common sense suggests that fewer adhesions should logically result in less pain, more pregnancies, fewer bowel obstructions and less long-term morbidity. We believe that 'fewer adhesions' is a good thing, but we have no controlled human trials to prove this. How much of a reduction in post-operative adhesions is necessary before it is clinically relevant? A single adhesion in the wrong anatomic location may be catastrophic. How do we measure this? Until these and other questions have been answered (if ever), we have nothing more than educated guesses that all these efforts are warranted.
Alice, Eloi, Magali and Robert: the lives of four patients with psoriasis and the therapeutic approaches of eight European experts
Authors: L. Dubertret, S. Chimenti, E. Christophers, E. Daudén, M. de Rie, C. E. M. Griffiths, K. Kragballe, M. Ståhle, G. Stingl
Journal: British Journal of Dermatology (2009)