tbuckley/cabot-search huggingface dataset:
Iron content in human alveolar macrophages
Authors: JL Corhay, G Weber, T Bury, S Mariz, I Roelandts, MF Radermecker
Journal: European Respiratory Journal (1992)

Intracellular iron can be estimated semi-quantitatively by histochemical determination using the ferrocyanide reagent's score. Particle-induced X-ray emission (PIXE) allows accurate determination of various elements including iron in cells and biological fluids. Both techniques have been used to measure iron in alveolar macrophages gathered by bronchoalveolar lavage. The purpose of this study was to investigate the clinical usefulness of the PIXE technique in occupational respiratory medicine and in various pulmonary diseases. Using the PIXE method, we measured the iron content of alveolar macrophages in healthy subjects, with and without occupational exposure to iron dust, and in patients with pulmonary diseases (chronic obstructive pulmonary disease (COPD), lung cancer, Goodpasture's syndrome). Our results were then compared with those obtained with the ferrocyanide reagent. Intramacrophagic iron was 0.33 +/- 0.21 micrograms.10(-6) (mean +/- SD) cells in healthy non-smoking subjects without occupational exposure. Intramacrophagic iron was increased in smokers, iron-steelworkers, and in patients with COPD or lung cancer even in the absence of pulmonary haemorrhage. The two patients with Goodpasture's syndrome had high intramacrophagic iron content. About 80% of the whole bronchoalveolar lavage fluid iron content was in the cells. Mean iron content of blood monocytes, lymphocytes and neutrophils of eight healthy subjects was significantly lower than that of alveolar macrophages. A significant correlation was found between iron determination by the PIXE method and the ferrocyanide reagent's score (r = 0.89). We conclude that intramacrophagic iron may be increased in steelworkers and subjects with pulmonary haemorrhage, but also in asymptomatic smokers, in COPD and lung cancer patients without occupational exposure to iron dust.
Prolonged Culture of Vaccine-Primed Lymphocytes Results in Decreased Antitumor Killing and Change in Cytokine Secretion
Authors: Jeffrey J. Sussman, Robin Parihar, Karen Winstead, Fred D. Finkelman
Journal: Cancer Research (2004)

Abstract Adoptive transfer of effector T cells has been used successfully to eliminate metastases in animal models. Because antitumor activity depends on the number of effector cells transferred, some human trials have used in vitro-repetitive activation and expansion techniques to increase cell number. We hypothesized that the prolonged culture period might contribute to the lack of human trial success by decreasing the potency of the effector T cells. Lymph nodes draining a progressively growing murine melanoma tumor transduced to secrete granulocyte/macrophage colony-stimulating factor were harvested and activated in vitro with anti-CD3 monoclonal antibody followed by expansion in IL-2 for a total of 5 days in culture. Some lymphocytes were reactivated and further expanded for a total of 9 days in culture. In vivo activity of the effector T cells was measured by the reduction in lung metastases and is shown to be dose dependent. The prolonged culture period resulted in nearly 3-fold more T cells but at least 8-fold less antitumor activity. This was accompanied by decreased secretion of the proinflammatory cytokine, IFN-γ, and increased secretion of the anti-inflammatory cytokine, IL-10. Thus, although increased cell number is important to maximize the effectiveness of adoptive immunotherapy, some culture conditions may actually be counterproductive in that decreases in cell potency can outweigh the benefits of increased cell numbers. The T-cell cytokine secretion pattern predicts decreased effector cell function and may explain the decreased antitumor effect.
TLR4 Links Podocytes with the Innate Immune System to Mediate Glomerular Injury
Authors: Miriam C. Banas, Bernhard Banas, Kelly L. Hudkins, Tomasz A. Wietecha, Masayuki Iyoda, Elisabeth Bock, Peter Hauser, Jeffrey W. Pippin, Stuart J. Shankland, Kelly D. Smith, Benjamin Stoelcker, Gang Liu, Hermann-Josef Gröne, Bernhard K. Krämer, Charles E. Alpers
Journal: Journal of the American Society of Nephrology (2008)

Toll-like receptors (TLR) classically recognize pathogen-associated danger signals but are also activated via endogenous ligands. For evaluation of their role in inflammatory kidney disease, the function of TLR was analyzed in two mouse models of cryoglobulinemic membranoproliferative glomerulonephritis (MPGN; mice transgenic for thymic stromal lymphopoietin [TSLP], with or without deletion of the Fcgamma receptor IIb). Expression of TLR1 through 9 and TLR11 mRNA was detectable in whole kidneys and in isolated glomeruli of wild-type mice, with TLR3 and TLR4 having the highest absolute levels of expression. TLR1, 2, and 4 were increased in TSLP transgenic mice and even higher in TSLP transgenic FcgammaRIIb-deficient mice. TLR5 through 9 and 11 were upregulated to similar degrees in TSLP transgenic and TSLP transgenic FcgammaRIIb-deficient mice. Immunohistochemical studies of nephritic glomeruli localized TLR4 protein to podocytes. Cultured podocytes also expressed TLR4, and stimulation with TLR4-specific ligands resulted in a marked induction of chemokines; this was reduced by specific knockdown of TLR4 with siRNA. Fibrinogen, a potential endogenous TLR4 ligand, was shown to induce a similar profile of chemokines. In conclusion, it was demonstrated that TLR4 is constitutively expressed by podocytes and is upregulated in MPGN, where it may mediate glomerular injury by modulating expression of chemokines; therefore, TLR4 may link podocytes with the innate immune system to mediate MPGN triggered by the deposition of immune complexes.
Precooling and percooling (cooling during exercise) both improve performance in the heat: a meta-analytical review
Authors: Coen C W G Bongers, Dick H J Thijssen, Matthijs T W Veltmeijer, Maria T E Hopman, Thijs M H Eijsvogels
Journal: British Journal of Sports Medicine (2014)

Background Exercise increases core body temperature (Tc), which is necessary to optimise physiological processes. However, excessive increase in Tc may impair performance and places participants at risk for the development of heat-related illnesses. Cooling is an effective strategy to attenuate the increase in Tc. This meta-analysis compares the effects of cooling before (precooling) and during exercise (percooling) on performance and physiological outcomes. Methods A computerised literature search, citation tracking and hand search were performed up to May 2013. 28 studies met the inclusion criteria, which were trials that examined the effects of cooling strategies on exercise performance in men, while exercise was performed in the heat (&gt;30°C). 20 studies used precooling, while 8 studies used percooling. Results The overall effect of precooling and percooling interventions on exercise performance was +6.7±0.9% (effect size (ES)=0.43). We found a comparable effect (p=0.82) of precooling (+5.7±1.0% (ES=0.44)) and percooling (+9.9±1.9% (ES=0.40)) to improve exercise performance. A lower finishing Tc was found in precooling (38.9°C) compared with control condition (39.1°C, p=0.03), while Tc was comparable between conditions in percooling studies. No correlation between Tc and performance was found. We found significant differences between cooling strategies, with a combination of multiple techniques being most effective for precooling (p&lt;0.01) and ice vest for percooling (p=0.02). Conclusions Cooling can significantly improve exercise performance in the heat. We found a comparable ES for precooling and percooling on exercise performance, while the type of cooling technique importantly impacts the effects. Precooling lowered the finishing core temperature, while there was no correlation between Tc and performance.
EXPERIMENTAL STUDIES UPON LYMPHOCYTES
Authors: Alwin M. Pappenheimer
Journal: The Journal of Experimental Medicine (1917)

The work of previous investigators gives the impression that it is easy to produce sera which both in vitro and upon injection are leukotoxic. At the same time the specificity of these leukotoxic sera for the particular type of cell used as antigen, and even for leukocytes in general, has been doubtful. The methods used have made certain possible factors of error unavoidable. Even careful washing of an organ or suspension cannot render it wholly blood-free, so that it is not surprising that the sera should be moderately hemolytic and hemagglutinative. Pearce has shown that the injection of very small amounts of blood is sufficient to evoke the production of immune hemolysins. When such sera are injected the lesions, as Pearce states, may be due in part to the production of hemagglutinative thrombi, although this hardly seems to apply to the changes in lymphoid tissue described by Flexner. On the other hand, the lymphotoxic effect of hemolytic sera may be due to the lymphocytes injected with the red cells. Our own experiments indicate that the lymphotoxic and agglutinative factors are to a considerable degree distinct from the hemolytic and hemagglutinative ones, since they can be separated from one another by absorption. Further evidence is presented that the small thymus cells are biologically related to, if not identical with the lymphocytes derived from lymph glands.
Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-α as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population
Authors: D. Castellano, X. Garcia del Muro, J.L. Pérez-Gracia, J.L. González-Larriba, M.V. Abrio, M.A. Ruiz, A. Pardo, C. Guzmán, S. Díaz Cerezo, E. Grande
Journal: Annals of Oncology (2009)

The purpose of this study is to evaluate the impact on the health-related quality of life (HRQoL) of sunitinib versus interferon-alpha (IFN-alpha) treatment in patients with metastatic renal cell carcinoma (mRCC).In all, 304 mRCC patients (European cohort) were randomized 1 : 1 to receive sunitinib (50 mg/day for 4 weeks, followed by 2 weeks off) or IFN-alpha (9 million units s.c. injection three times/week). The following questionnaires were completed (days 1 and 28 per cycle): Functional Assessment of Cancer Therapy-General (FACT-G), the FACT-Kidney Symptom Index and the EuroQol Group's EQ-5D self-report questionnaire (EQ-5D). Results correspond to an ongoing trial with progression-free survival time as primary end point, and patients were still being followed up. Data were analyzed using repeated measures mixed effects models (MEMs) that allow the inclusion of initial differences and uncompleted repeated measures, with the assumption of data missing at random. Six-cycle results were included.Results consistently showed that patients in sunitinib group experienced statistically significantly milder kidney-related symptoms, better cancer-specific HRQoL and general health status (in social utility scores) during the study period as measured by these patient-reported outcome end points. No statistical differences between groups were found on the FACT-G physical well-being subscale or the EQ-5D VAS values.Results from MEM showed the sunitinib's benefit on HRQoL compared with IFN-alpha.
Sustained Efficacy of Allert Allergy Vaccine after a Second Birch Pollen Season: A Phase IIb
Authors: Francois Spertini, Marek Jutel, Lars Jacobsen, Frederic de Blay, Margitta Worm, Gilles Della Corte, Alexander Kettner, Vincent Charlon, Christophe Reymond
Journal: Journal of Allergy and Clinical Immunology (2015)
T Cell Receptor Gene Rearrangement Lineage Analysis Reveals Clues for the Origin of Highly Restricted Antigen-specific Repertoires
Authors: Abdelbasset Hamrouni, Anne Aublin, Philippe Guillaume, Janet L. Maryanski
Journal: The Journal of Experimental Medicine (2003)

Due to ordered, stage-specific T cell receptor (TCR)-β and -α locus gene rearrangements and cell division during T cell development, a given, ancestral TCR-β locus VDJ rearrangement might be selected into the mature T cell repertoire as a small cohort of “half-sibling” progeny expressing identical TCR-β chains paired with different TCR-α chains. The low frequency of such a cohort relative to the total αβ TCR repertoire precludes their direct identification and characterization in normal mice. We considered it possible that positive selection constraints might limit the diversity of TCR-α chains selected to pair with β chains encoded by an ancestral VDJ-β rearrangement. If so, half-sibling T cells expressing structurally similar, but different TCR-α chains might recognize the same foreign antigen. By single cell polymerase chain reaction analysis of antigen-specific TCRs selected during a model anti-tumor response, we were able to identify clusters of T cells sharing identical VDJ-β rearrangements but expressing different TCR-α chains. The amplification of residual DJ-β rearrangements as clonal markers allowed us to track T cells expressing different TCR-α chains back to a common ancestral VDJ-β rearrangement. Thus, the diversity of TCR-α's selected as partners for a given VDJ-β rearrangement into the mature TCR repertoire may indeed be very limited.
An essential role for the MAL protein in targeting Lck to the plasma membrane of human T lymphocytes
Authors: Olga Antón, Alicia Batista, Jaime Millán, Laura Andrés-Delgado, Rosa Puertollano, Isabel Correas, Miguel A. Alonso
Journal: The Journal of Experimental Medicine (2008)

The MAL protein is an essential component of the specialized machinery for apical targeting in epithelial cells. The src family kinase Lck plays a pivotal role in T cell signaling. We show that MAL is required in T cells for efficient expression of Lck at the plasma membrane and activation of IL-2 transcription. To investigate the mechanism by which MAL regulates Lck targeting, we analyzed the dynamics of Lck and found that it travels to the plasma membrane in specific transport carriers containing MAL. Coimmunoprecipitation experiments indicated an association of MAL with Lck. Both carrier formation and partitioning of Lck into detergent-insoluble membranes were ablated in the absence of MAL. Polarization of T cell receptor for antigen (TCR) and microtubule-organizing center to immunological synapse (IS) were also defective. Although partial correction of the latter defects was possible by forced expression of Lck at the plasma membrane, their complete correction, formation of transport vesicles, partitioning of Lck, and restoration of signaling pathways, which are required for IL-2 transcription up-regulation, were achieved by exogenous expression of MAL. We concluded that MAL is required for recruitment of Lck to specialized membranes and formation of specific transport carriers for Lck targeting. This novel transport pathway is crucial for TCR-mediated signaling and IS assembly.
Oral health and impact on performance of athletes participating in the London 2012 Olympic Games: a cross-sectional study
Authors: I Needleman, P Ashley, A Petrie, F Fortune, W Turner, J Jones, J Niggli, L Engebretsen, R Budgett, N Donos, T Clough, S Porter
Journal: British Journal of Sports Medicine (2013)

Background Oral health is important both for well-being and successful elite sporting performance. Reports from Olympic Games have found significant treatment needs; however, few studies have examined oral health directly. The aim of this study was to evaluate oral health, the determinants of oral health and the effect of oral health on well-being, training and performance of athletes participating in the London 2012 Games. Methods Cross-sectional study at the dental clinic within the Polyclinic in the athletes’ village. Following informed consent, a standardised history, clinical examination and brief questionnaire were conducted. Results 302 athletes from 25 sports were recruited with data available for 278. The majority of athletes were from Africa, the Americas and Europe. Overall, the results demonstrated high levels of poor oral health including dental caries (55% athletes), dental erosion (45% athletes) and periodontal disease (gingivitis 76% athletes, periodontitis 15% athletes). More than 40% of athletes were ‘bothered’ by their oral health with 28% reporting an impact on quality of life and 18% on training and performance. Nearly half of the participants had not undergone a dental examination or hygiene care in the previous year. Conclusions The oral health of athletes attending the dental clinic of the London 2012 Games was poor with a resulting substantial negative impact on well-being, training and performance. As oral health is an important element of overall health and well-being, health promotion and disease prevention interventions are urgently required to optimise athletic performance.
Training the child athlete: physical fitness, health and injury
Authors: Cordelia W Carter, Lyle J Micheli
Journal: British Journal of Sports Medicine (2011)

The number of children and adolescents participating in organised athletic activities worldwide is increasing. However, physical fitness levels among youth are lower today than in previous decades. The combination of increased exposure and decreased preparedness for sports participation has led to an epidemic of both acute and chronic sports-related injuries in this population. Poor physical fitness, in addition to having negative health consequences, seems to be a risk factor for sports-related injury. Accurate injury surveillance data are required to better define the magnitude of the problem of injury in youth sports, as well as to identify specific risk factors for injury. From these data, targeted intervention strategies incorporating fitness training may be developed with the goal of preventing sports-related injury. Preliminary experience with several specific injury patterns—anterior cruciate ligament injuries and ankle sprains—has demonstrated the efficacy of such targeted prevention strategies.
Doctors: fighting fit or couch potatoes?
Authors: K Gupta, L Fan
Journal: British Journal of Sports Medicine (2008)

Objective:  To evaluate how Doctors compared to the UK average, in terms of Department-of-Health recommended thirty-minutes of moderate-exercise, at least five times-per-week. Further hypotheses tested include whether those with on-site gym facilities are more likely to meet the recommendations, than those without, and whether those meeting DOH-recommendations at medical school, continue as Doctors.   Design:  Each candidate answered 21 questions including demographics, exercise-habits and general-health. Data were analysed statistically using Student9s t-test, Fisher9s, McNemara9s test.   Setting:  Bedford Hospital, West Middlesex University Hospital.   Participants:  61 foundation and specialty trainees were randomly recruited.   Interventions:  Independent variable was the presence of exercise facilities.   Main outcome measures:  The number of participants currently meeting DOH-recommendations. We recorded the reason each participant gave, if they did not do so.   Results:  32 female, 29 male, median BMI 23.5, 6% smokers; 11% ex-smokers, ~10% drank excess alcohol, (n=61). Only 21% met DOH-exercise-recommendations, significantly lower than national average (p   Conclusion:  The Doctors in this study exercise less than average. However, those with on-site facilities did not meet DOH-recommendations more than those without. Few of those who met the DOH recommendations as medical students, continued as Doctors. This is especially worrying. The combination of a heavy work-load, lack of time and poor motivation contributes to the lack of exercise.
In Vitro and in Vivo Immunomodulatory Effects of RDP1258, a Novel Synthetic Peptide
Authors: COLM C. MAGEE, HARUHITO AZUMA, ANDREAS KNOFLACH, MARK D. DENTON, ANIL CHANDRAKER, SUHASINI IYER, ROLAND BUELOW, MOHAMED SAYEGH
Journal: Journal of the American Society of Nephrology (1999)

Abstract. Peptides derived from certain regions of human class I MHC molecules are known to have immunomodulatory effects. In particular, amino acid residues 75-84 of the HLA-B7 and HLA-B2702 molecules have demonstrated allele nonspecific immunosuppression in several animal transplant models. There is evidence that these effects are mediated by binding to intracellular heat shock proteins, including heme oxygenase-1. A new derivative of these peptides, RDP1258, was developed using a novel computer-assisted rational design technique. In vitro , RDP1258 peptide inhibited rat heme oxygenase activity in a dose-dependent manner. Similar to observations made with other in vitro heme oxygenase inhibitors, in vivo administration of RDP1258 peptide to naïve rats resulted in upregulation of splenic heme oxygenase activity. The effects of the peptide on alloimmune responses were then tested. Addition of RDP1258 to rat and human mixed leukocyte reactions inhibited proliferation in a dose-dependent manner. In a rat renal transplantation model, peptide therapy combined with a sub-therapeutic dose of cyclosporin A significantly prolonged allograft survival. These data provide further evidence that modulation of the heat shock protein heme oxygenase by rationally designed peptides affects immune effector functions and may allow the development of novel immunomodulatory strategies in organ transplantation.
F 1 F O-ATPase Activity and ATP Dependence of Mitochondrial Energization in Proximal Tubules after Hypoxia/Reoxygenation
Authors: Thorsten Feldkamp, Andreas Kribben, Joel M. Weinberg
Journal: Journal of the American Society of Nephrology (2005)

Isolated kidney proximal tubules subjected to hypoxia/reoxygenation (H/R) have incomplete recovery of mitochondrial membrane potential (DeltaPsi(m)) that can be improved, but not normalized, by ATP in permeabilized cells as measured by safranin O uptake. In these studies, the mechanisms for the decreased DeltaPsi(m) in the tubules after H/R are further investigated and impairment of the function of the mitochondrial F(1)F(O)-ATPase is assessed. Normoxic control tubules had a small ATP-dependent component to DeltaPsi(m), but it required low micromolar levels of ATP, not the millimolar levels needed to support DeltaPsi(m) in tubules de-energized with rotenone or after H/R. Micromolar levels of ATP did not improve DeltaPsi(m) after either mild or severe H/R injury. The dependence of DeltaPsi(m) on millimolar levels of ATP after H/R decreased over time during reoxygenation. ATP hydrolysis by the oligomycin-sensitive, mitochondrial F(1)F(O)-ATPase was well preserved after H/R as long as Mg(2+) was available, indicating that function of both the F(1)F(O)-ATPase and of the adenine nucleotide translocase, which delivers nucleotides to it, are largely intact. However, ATP hydrolysis by the ATPase did not restore DeltaPsi(m) as much as expected from the rate of ATP utilization. These findings, taken together with the observation that substrate-supported generation of DeltaPsi(m) is impaired despite intact electron transport, make it likely that uncoupling plays a major role in the mitochondrial dysfunction in proximal tubules during H/R.
Enhanced Recovery After Surgery (ERAS ® ) multimodal programme as experienced by pancreatic surgery patients: Findings from an Italian qualitative study
Authors: Emanuele Galli, Cristina Fagnani, Ilaria Laurora, Carmen Marchese, Giovanni Capretti, Nicolò Pecorelli, Elisabetta Marzo, Alvisa Palese, Lucia Zannini
Journal: International Journal of Surgery (2015)