tbuckley/cabot-search huggingface dataset:
Changes in haematological indices and swimming performance after intermittent normobaric hypoxia exposure: a case study
Authors: A Y W Tan, G Urquhart
Journal: British Journal of Sports Medicine (2010)

The purpose of this case study was to quantify the changes in basic haematological indices and swimming performance after intermittent normobaric hypoxia exposure (IHE) in two Olympian swimmers. Two female swimmers, middle-distance (MD) age 18 years, and long-distance (LD) age 22 years, completed a 15-day continuous regimen of 60-min a day IHE. Following routine pool training in the morning, swimmers were exposed to hypoxia for 6 min by having them breathe through a simulated device that restricted delivery of O<sub>2</sub> to the body. This was followed by 4 min of normoxia breathing room air. Hypoxic conditions were replicated in a graded declination in percentage of O<sub>2</sub> saturation as recommended by manufacturer: 90% (for the first 2 days), 85% (second 2 days), 80% (third 2 days) and 75% (last 9 days). Before and after the IHE, blood samples were collected for the analysis of red cell count (RBC), haemoglobin concentration (Hb) and haematocrit (Hct) while a 16×100-m incremental swimming test (with the final 100 m in all-out effort) was conducted to track performance changes. There were no significant changes in RBC, Hb or Hct of either swimmer after IHE. Heart rate during the graded swim test was the same before and after IHE. Rating of perceived exertion during each stage was lowered in MD but unaltered in LD. Performance time of 100 m all-out effort showed 4.8% and 1.6% declines in MD and LD, respectively. IHE does not seem to bring about positive changes in haematological response and swimming performance of highly competitive female swimmers. This might be because the hypoxic dose of IHE in the present study did not reach the threshold stimulus for haematological and performance benefits.
Specific Subpopulation Involved in Allergic Delayed Responses to Amoxicillin in an in Vitro System with Autologous Dendritic Cells
Authors: R. R-Pena, S. Lopez, C. Antunez, P. Chaves, C. Mayorga, M.J. Torres, T.D. Fernandez, J.A. Cornejo-Garcia, M. Blanca
Journal: Journal of Allergy and Clinical Immunology (2007)
Association of Corticosteroid Dose and Route of Administration With Risk of Treatment Failure in Acute Exacerbation of Chronic Obstructive Pulmonary Disease
Authors: Peter K. Lindenauer
Journal: JAMA (2010)

Systemic corticosteroids are beneficial for patients hospitalized with acute exacerbation of chronic obstructive pulmonary disease (COPD); however, their optimal dose and route of administration are uncertain.To compare the outcomes of patients treated with low doses of steroids administered orally to those treated with higher doses administered intravenously.A pharmacoepidemiological cohort study conducted at 414 US hospitals involving patients admitted with acute exacerbation of COPD in 2006 and 2007 to a non-intensive care setting and who received systemic corticosteroids during the first 2 hospital days.A composite measure of treatment failure, defined as the initiation of mechanical ventilation after the second hospital day, inpatient mortality, or readmission for acute exacerbation of COPD within 30 days of discharge. Length of stay and hospital costs.Of 79,985 patients, 73,765 (92%) were initially treated with intravenous steroids, whereas 6220 (8%) received oral treatment. We found that 1.4% (95% confidence interval [CI], 1.3%-1.5%) of the intravenously and 1.0% (95% CI, 0.7%-1.2%) of the orally treated patients died during hospitalization, whereas 10.9% (95% CI, 10.7%-11.1%) of the intravenously and 10.3% (95% CI, 9.5%-11.0%) of the orally treated patients experienced the composite outcome. After multivariable adjustment, including the propensity for oral treatment, the risk of treatment failure among patients treated orally was not worse than for those treated intravenously (odds ratio [OR], 0.93; 95% CI, 0.84-1.02). In a propensity-matched analysis, the risk of treatment failure was significantly lower among orally treated patients (OR, 0.84; 95% CI, 0.75-0.95), as was length of stay and cost. Using an adaptation of the instrumental variable approach, increased rate of treatment with oral steroids was not associated with a change in the risk of treatment failure (OR for each 10% increase in hospital use of oral steroids, 1.00; 95% CI, 0.97-1.03). A total of 1356 (22%) patients initially treated with oral steroids were switched to intravenous therapy later in the hospitalization.Among patients hospitalized for acute exacerbation of COPD low-dose steroids administered orally are not associated with worse outcomes than high-dose intravenous therapy.
Comparison of the dose-response curves obtained by forced oscillation and plethysmography during carbachol inhalation
Authors: T Chinet, G Pelle, I Macquin-Mavier, H Lorino, A Harf
Journal: European Respiratory Journal (1988)

We compared the cumulative dose-response curves obtained during carbachol inhalation by simultaneous measurements of airway specific conductance (sGaw) and respiratory conductance, in 23 subjects with or without bronchial hyperresponsiveness. The sGaw was measured by a body plethysmograph, whilst the random noise forced oscillation technique (FOT) was used to determine respiratory conductance. The sGaw was compared to respiratory conductance extrapolated to zero frequency (Grs0). Bronchial sensitivity was assessed by the threshold dose of carbachol (TD) that induced a decrease in sGaw and Grs0 of twice the baseline coefficient of variation. Bronchial responsiveness was assessed by the slopes (S) of the individual dose-response curves. The TD and S values obtained by FOT and by plethysmography were closely correlated (p less than 0.001). The carbachol doses inducing a 50% reduction in sGaw were equivalent to those causing a 42% reduction in Grs0 (r = 0.90; p less than 0.001). During bronchial challenge testing, FOT provides comparable information in terms of bronchial sensitivity and responsiveness to that supplied by plethysmography.
L-selectin and intercellular adhesion molecule 1 mediate lymphocyte migration to the inflamed airway/lung during an allergic inflammatory response in an animal model of asthma
Authors: Efthimia Keramidaris, Toby D. Merson, Douglas A. Steeber, Thomas F. Tedder, Mimi L.K. Tang
Journal: Journal of Allergy and Clinical Immunology (2001)
The STAT3 DNA-Binding Domain Mediates Interaction with NF-κB p65 and Inducible Nitric Oxide Synthase Transrepression in Mesangial Cells
Authors: Zhiyuan Yu, Bruce C. Kone
Journal: Journal of the American Society of Nephrology (2004)

Signal transducer and activator of transcription 3 (STAT3) and nuclear factor kappaB (NF-kappaB) are important transcription factors involved in glomerulonephritis and other inflammatory processes, including transcription of the inducible nitric oxide synthase (iNOS) gene. The ability of STAT3 to interact physically with NF-kappaB p65 in glomerular mesangial cells and thereby to inhibit NF-kappaB-mediated transactivation of the iNOS gene was demonstrated previously. STAT3 is a modular protein with several structurally and functionally defined domains. For defining STAT3 domains that interact with NF-kappaB p65, (35)S-labeled proteins that corresponded to each STAT3alpha domain were synthesized, and their ability to bind specifically a GST-NF-kappaB p65 fusion protein in GST pulldown assays was tested. The coiled-coil and DNA-binding domains were specifically retained by GST-NF-kappaB p65, whereas the N-terminal, linker domain, Src homology 2 domain, and transcriptional activation domain failed to interact with NF-kappaB p65. Deletion of the region L(358) through I(369) of the STAT3 DNA-binding domain greatly reduced binding to GST-NF-kappaB p65. Alanine substitution mutations at four highly conserved residues-L(358), N(359), K(363), and V(366)-in this region greatly abrogated the ability of STAT3 to bind NF-kappaB p65. Moreover, in contrast to the transrepression afforded by wild-type STAT3alpha, a STAT3alpha construct harboring these mutations, failed to suppress endogenous NO production and to transrepress iNOS promoter-reporter and kappaB element-reporter constructs in IL-beta-stimulated mesangial cells. These data reveal a novel role for the DNA-binding domain in the physical and functional coupling of STAT3 to NF-kappaB p65 that is important for regulating the transcriptional activity of iNOS and likely other NF-kappaB p65 responsive genes that are important for mesangial cell responses.
Prevention of aspirin-induced faecal blood loss by prostaglandin E2.
Authors: M M Cohen, G Cheung, D M Lyster
Journal: Gut (1980)

Prostaglandins have been shown in animal laboratory studies to be capable of protecting the gastrointestinal tract against injury by exogenous agents. This study was conducted to determine if prostaglandin E2 (PGE2), which is native to the human gastric mucosa, could influence the increase in faecal blood loss associated with the ingestion of aspirin (ASA). A randomised double-blind study was performed on 27 healthy men. Faecal blood loss was measured by the 51Cr labelled red cell technique. ASA (600 mg four times daily) caused a significant increase in faecal blood loss. PGE2 (1 mg four times daily) had no effect on faecal blood loss when administered alone. When given in addition to ASA it resulted in a faecal blood loss not significantly different from control. No significant alteration in intestinal transit occurred. It is concluded that PGE2 protects man from the gastrointestinal injury associated with ASA.
TNFR2 expression on non-bone marrow-derived cells is crucial for lipopolysaccharide-induced septic shock and downregulation of soluble TNFR2 level in serum
Authors: Shubai Liu, Lijie Rong, Jingjing Deng, Xiaopu Zhao, Xiaoman Liu, Xia Xu, Zhihai Qin
Journal: Cellular and Molecular Immunology (2011)
ENVIRONMENT AND CONTAMINANTS IN TRADITIONAL FOOD SYSTEMS OF NORTHERN INDIGENOUS PEOPLES
Authors: H. V. Kuhnlein, H. M. Chan
Journal: Annual Review of Nutrition (2000)

Traditional food resources of indigenous peoples are now recognized as containing a variety of environmental contaminants which reach food species through local or long-range transport avenues. In this chapter we review the published reports of contaminants contained in traditional food in northern North America and Europe as organochlorines, heavy metals, and radionuclides. Usually, multiple contaminants are contained in the same food species. Measurement of dietary exposure to these environmental contaminants is reviewed, as are major issues of risk assessment, evaluation, and management. The dilemma faced by indigenous peoples in weighing the multiple nutritional and socioeconomic benefits of traditional food use against risk of contaminants in culturally important food resources is described.
Expression of matrix metalloproteinases in patients with Wegener's granulomatosis
Authors: V Bjerkeli
Journal: Annals of the Rheumatic Diseases (2004)

<b>Background:</b> Enhanced activity of matrix metalloproteinases (MMPs) has been reported to have a pathogenic role in several diseases such as cancer and cardiovascular disorders, and seems also to play a part in certain autoimmune diseases. <b>Objective:</b> To examine whether enhanced MMP activity may also have a role in the pathogenesis of Wegener's granulomatosis (WG). <b>Methods:</b> In a study group of 15 patients with WG and 15 controls, plasma levels and gene expression were measured in freshly isolated peripheral blood mononuclear cells (PBMCs) of several MMPs and their endogenous inhibitors (that is, tissue inhibitors of metalloproteinases (TIMPs)) by enzyme immunoassays and RNase protection assay, respectively. <b>Results:</b> Whereas patients with WG in remission had enhanced gene expression of several MMPs and TIMPs in PBMCs, those with active disease had a selective up regulation of MMP-2 and MMP-8 compared with healthy controls, and a down regulation of TIMP-1 and TIMP-3 compared with other patients with WG. Moreover, plasma levels of TIMP-1 and MMP-8 correlated significantly with C reactive protein levels, further supporting an association between activation of the MMP/TIMP system and disease activity in WG. Finally, these changes in MMP/TIMP expression in WG were accompanied by increased total MMP activity in PBMC supernatants, particularly in those with active disease, suggesting a matrix degrading net effect. <b>Conclusion:</b> These findings suggest that disturbed MMP and TIMP activity has a role in the pathogenesis of WG.
Internet use by cancer patients: should oncologists ‘prescribe’ accurate web sites in combination with chemotherapy? A survey in a Spanish cohort
Authors: M. López-Gómez, C. Ortega, I. Suárez, G. Serralta, R. Madero, C. Gómez-Raposo, M. Sereno, E. Casado, E. Espinosa, F. Lobo, J. Feliu
Journal: Annals of Oncology (2011)
Long-term follow-up after risk-adapted treatment in clinical stage 1 (CS1) nonseminomatous germ-cell testicular cancer (NSGCT) implementing adjuvant CVB chemotherapy. A SWENOTECA study
Authors: T. Tandstad, G. Cohn-Cedermark, O. Dahl, U. Stierner, E. Cavallin-Stahl, R.M. Bremnes, O. Klepp
Journal: Annals of Oncology (2010)
Vaccination with Mage-3a1 Peptide–Pulsed Mature, Monocyte-Derived Dendritic Cells Expands Specific Cytotoxic T Cells and Induces Regression of Some Metastases in Advanced Stage IV Melanoma
Authors: Beatrice Thurner, Ina Haendle, Claudia Röder, Detlef Dieckmann, Petra Keikavoussi, Helmut Jonuleit, Armin Bender, Christian Maczek, Doris Schreiner, Peter von den Driesch, Eva B. Bröcker, Ralph M. Steinman, Alexander Enk, Eckhart Kämpgen, Gerold Schuler
Journal: The Journal of Experimental Medicine (1999)

Dendritic cells (DCs) are considered to be promising adjuvants for inducing immunity to cancer. We used mature, monocyte-derived DCs to elicit resistance to malignant melanoma. The DCs were pulsed with Mage-3A1 tumor peptide and a recall antigen, tetanus toxoid or tuberculin. 11 far advanced stage IV melanoma patients, who were progressive despite standard chemotherapy, received five DC vaccinations at 14-d intervals. The first three vaccinations were administered into the skin, 3 × 106 DCs each subcutaneously and intradermally, followed by two intravenous injections of 6 × 106 and 12 × 106 DCs, respectively. Only minor (less than or equal to grade II) side effects were observed. Immunity to the recall antigen was boosted. Significant expansions of Mage-3A1–specific CD8+ cytotoxic T lymphocyte (CTL) precursors were induced in 8/11 patients. Curiously, these immune responses often declined after the intravenous vaccinations. Regressions of individual metastases (skin, lymph node, lung, and liver) were evident in 6/11 patients. Resolution of skin metastases in two of the patients was accompanied by erythema and CD8+ T cell infiltration, whereas nonregressing lesions lacked CD8+ T cells as well as Mage-3 mRNA expression. This study proves the principle that DC “vaccines” can frequently expand tumor-specific CTLs and elicit regressions even in advanced cancer and, in addition, provides evidence for an active CD8+ CTL–tumor cell interaction in situ as well as escape by lack of tumor antigen expression.
The timed walk test as a measure of severity and survival in idiopathic pulmonary fibrosis
Authors: T. S. Hallstrand, L. J. Boitano, W. C. Johnson, C. A. Spada, J. G. Hayes, G. Raghu
Journal: European Respiratory Journal (2005)

Idiopathic pulmonary fibrosis (IPF) is a relentlessly progressive disease with a median survival of ∼3 yrs. Measurements of airflow and lung volumes at rest are generally used to monitor the clinical course in this disorder. This study was designed to determine if a modified version of the 6-min walk test, called the timed walk test, accurately characterises disease severity and survival in IPF. The study population consisted of 28 patients with well-characterised progressive IPF. The timed walk test and concurrent measures of disease severity were assessed at baseline. Participants were prospectively followed for ≥4 yrs to determine the relationship between parameters of the timed walk test and survival. There were strong correlations between the end-exercise saturation and walk-velocity parameters of the timed walk test and diffusing capacity, and arterial oxygen tension at rest. In univariate Cox proportional-hazards models, end-exercise saturation, change in saturation with exercise, walk distance and walk velocity were associated with survival. In unadjusted logistic regression models, odds of death at 2 yrs were associated with the same parameters. In conclusion, the timed walk test relates to disease severity and long-term outcome in progressive idiopathic pulmonary fibrosis.
The Enigmatic Planctomycetes May Hold a Key to the Origins of Methanogenesis and Methylotrophy
Authors: Ludmila Chistoserdova, Cheryl Jenkins, Marina G. Kalyuzhnaya, Christopher J. Marx, Alla Lapidus, Julia A. Vorholt, James T. Staley, Mazy E. Lidstrom
Journal: Molecular Biology and Evolution (2004)

Methanogenesis and methane oxidation are the major biological processes affecting the global cycling of the powerful greenhouse gas methane. To carry out the two alternative bioconversions, Nature has cleverly recycled key reactions for the C1 transfers between the oxidation levels of formaldehyde and formate, and these involve analogous enzyme systems and common specialized cofactors, methanopterin and methanofuran. Until recently, the distribution of these functions has been limited to methanogenic archaea and methylotrophic proteobacteria, and their evolutionary history remained obscure. Single interdomain lateral transfer of the respective genes has been suggested to play a role. Here we show that genes for C1 transfer reactions linked to methanopterin and methanofuran are also present in diverse representatives of the enigmatic bacterial clade, the Planctomycetes. Phylogenetic analysis places the planctomycete sequences as distantly from their archaeal counterparts as from their proteobacterial counterparts, suggesting novel scenarios for the evolution of the C1 transfer functions in both methanogens and methylotrophs. This finding suggests a possible role for Planctomycetes in the evolution of the methane cycle on Earth.
TGM3, a candidate tumor suppressor gene, contributes to human head and neck cancer
Authors: Xiangbing Wu, Wei Cao, Xu Wang, Jianjun Zhang, Zhongjing Lv, Xing Qin, Yadi Wu, Wantao Chen
Journal: Molecular Cancer (2013)

Abstract Background In our previous study using oligonucleotide microarrays, we revealed that transglutaminase 3 (TGM3) was remarkably down-regulated in head and neck cancer (HNC). However, the potential of TGM3 as a useful biomarker or molecular target for HNC is unclear. Methods The transcriptional and post-translational status of TGM3 in HNC cell lines and specimens was detected using real-time PCR and western blot analysis. Bisulfate-treated DNA sequencing was used to analyze the molecular mechanism of TGM3 gene silencing. In addition, the effects of TGM3 on the proliferation, colony formation and induction of apoptosis in vitro and tumorigenicity in vivo were investigated through exogenous expression of TGM3 in HNC cells. Immunohistochemistry was used to evaluate TGM3 expression in large HNC samples. Results TGM3 was down-regulated in HNC samples and cell lines ( P &lt; 0.0001). The hypermethylation of a promoter CpG island was one of the mechanisms of silencing the TGM3 gene in HNC. Exogenous expression of TGM3 in HNC cells could inhibit the proliferation and enhance the apoptosis of HNC cells in vitro and suppress tumor growth in vivo . In addition, TGM3 protein levels were strongly associated with the pathological differentiation of HNC tissues ( P = 0.0037). Survival analysis revealed that low TGM3 expression was associated with worse overall survival ( P = 0.0002), and TGM3 expression level was an independent predictor in patients with HNC. Conclusions The studies prove that TGM3, as a candidate tumor suppressor, contributes to the carcinogenesis and development of HNC and may serve as a useful biomarker for patients with HNC.
Folate status of gastrointestinal epithelial cells is not predicted by serum and red cell folate values in replete subjects.
Authors: J Meenan, E O'Hallinan, S Lynch, A Molloy, J McPartlan, J Scott, D G Weir
Journal: Gut (1996)

Localised folate deficiency has been implicated in colonic carcinogenesis and supplementation has been proposed for certain populations at risk. However, identifying those groups that may benefit is difficult as the relation between blood folate and gut epithelial cell values is unknown. The aim of this study was to define this relation. Epithelial cells mean (SEM) (sigmoid: 5.35 (0.56) x 10(6) cells, caecum: 6.6 (0.71) x 10(6) cells, duodenum: 4.0 (0.62) x 10(6) cells) were isolated from four endoscopic mucosal biopsy specimens (n = 25) by incubation with dithiothreitol (three hours) and EDTA (one hour). Lamina propria contamination was < 1%, with < 6% intraepithelial lymphocytes. Folate assay of isolates showed sigmoid colon folate content to be 20.1 (1.8) pg/micrograms DNA (10.2-46.6). In the same subject, caecal folate concentrations were lower (p < 0.01, n = 11) than sigmoid values, whereas duodenal isolates mirrored those of the sigmoid (19.4 (2.9) v 20.5 (3.2), n = 5). Sigmoid folate values were consistent over one to three weeks (n = 3). In a single case with blood folate deficiency, colonic values were normal. Serum folate and red cell folate correlated poorly with sigmoid epithelial cell folate content (r = 0.41, p = 0.063 and r = 0.17, p > 0.05 respectively). This study reports a modified ion-chelation isolation method for colonic biopsy specimens that yields large numbers of viable epithelial cells. Cell folate values remain constant with time though vary with intestinal region. The inability of serum or red cell folate values to predict those of the sigmoid epithelium suggests that they cannot identify those patients that might benefit from folate supplements.
Closed-Chest Microdialysis to Measure Antibiotic Penetration into Human Lung Tissue
Authors: HARALD HERKNER, MICHAEL ROLF MÜLLER, NICOLE KREISCHITZ, BERNHARD X. MAYER, MARTIN FROSSARD, CHRISTIAN JOUKHADAR, NIKOLAS KLEIN, EDITH LACKNER, MARKUS MÜLLER
Journal: American Journal of Respiratory and Critical Care Medicine (2002)

The majority of bacterial lung infections are localized to the interstitial space fluid, which is therefore an important target site for antimicrobial chemotherapy. Direct measurement of interstitial concentrations of antimicrobial agents in human lung tissue would allow for a more informed approach to appropriate dosing of antimicrobial agents, but until now this was beyond technical reach. In this exploratory pharmacokinetic study, we measured the time versus concentration profile of cefpirome after a single intravenous dose administration of 2 g in the lung interstitial fluid by flexible microdialysis catheters, which were implanted during lung surgery for pulmonary tumors in five patients. Cefpirome concentrations in lung interstitial fluid were 66% of corresponding plasma values within the first 240 min, and exceeded minimal inhibitory concentrations of most relevant bacteria. The experimental procedure was well tolerated by the patients and no adverse events were observed. The present study provides evidence for the first time that closed chest microdialysis of the human lung is a feasible and safe method to measure lung concentrations in patients in vivo. The present data also corroborate the use of cefpirome as a valuable agent in the treatment of lung infections with most extracellular bacteria.