tbuckley/cabot-search huggingface dataset:
Intrahepatic HCV levels in chronic HCV infection Reply
Authors: M BONACINI, A G REDEKER;, G H HAYDON
Journal: Gut (1999)

<h3>Background</h3> We hypothesised that increased oxidative stress, as present in the airways of asthma and chronic obstructive pulmonary disease (COPD) patients, induces epithelial damage and reduces epithelial responsiveness to suppressive effects of corticosteroids on proinflammatory cytokine production and barrier function. <h3>Methods</h3> We induced oxidative stress by H<sub>2</sub>O<sub>2</sub> and/or cigarette smoke extract (CSE) in human bronchial epithelial 16HBE cells and primary bronchial epithelial cells (PBEC) derived by brushings from asthma patients, COPD patients, and smoking and non-smoking control individuals. We investigated effects of budesonide on barrier function (electrical resistance) and TNF-α-induced proinflammatory cytokine production (IL-8/CXCL8, granulocyte macrophage-colony stimulating factor (GM-CSF)). <h3>Results</h3> We observed that H<sub>2</sub>O<sub>2</sub> and CSE reduce epithelial resistance. Budesonide significantly counteracted this effect, likely by protection against epidermal growth factor receptor-dependent cell-cell contact disruption. Furthermore, budesonide suppressed proinflammatory cytokine production. H<sub>2</sub>O<sub>2</sub> pretreatment reduced this effect of budesonide on cytokine production in both 16HBE cells and PBECs. Importantly, PBECs from asthma and COPD patients were less sensitive to budesonide with respect to cytokine production and barrier function than PBECs from control subjects. <h3>Conclusions</h3> Together, our data indicate that budesonide suppresses epithelial proinflammatory responses and barrier dysfunction and that oxidative stress reduces these effects in airway epithelium from asthma and COPD patients. Therefore, restoration of corticosteroid responsiveness in asthma and COPD may act to improve the airway epithelial barrier.
Resistance to Non-Strain-Specific Variant Tumor Cells by &lt;italic&gt;H-2&lt;/italic&gt; Allogeneic Mice Receiving Strain-Specific Cells&lt;xref ref-type="fn" rid="FN2"&gt;2&lt;/xref&gt;
Authors: James Forman, Melvin M. Ketchel
Journal: JNCI Journal of the National Cancer Institute (1972)

A non-strain-specific (NSS) variant of the L5178 tumor line could grow in H-2 allogeneic hosts, whereas a strain-specific (SS) subline could not. When NSS and SS cells were injected simultaneously into H-2 allogeneic hosts, both were rejected. This effect was not seen in irradiated or non-H-2 allogeneic mice. The concentration of alloantigenic determinants H-2.3 and H-2.4 did not differ in the NSS and SS tumor cells. Apparently, although both SS and NSS cells had equivalent amounts of antigen on their surfaces and were susceptible to the homograft reaction in vivo, NSS cells could not sensitize H-2 allogeneic mice so that they could reject the tumor.
Does oxygen pulled on the cart help or impair ambulation in COPD patients with resting and exertional hypoxaemia
Authors: Jacek Nasilowski, Tadeusz Przybylowski, Ryszarda Chazan
Journal: European Respiratory Journal (2013)

Oxygen increases exercise capacity in COPD patients with resting (RH) and exertional hypoxaemia (EH). Pulling the oxygen source on a wheeled cart is beneficial versus carrying it on a shoulder. However, pulling the cart may impair walking speed and reduce the possibility of ambulation. The aim of the study was to verify if walking with oxygen canister pulled by patient on a cart is beneficial versus walking without any load.

COPD patients with RH and EH in random order performed 2 standardized 6-min walking tests: without oxygen supplementation and with oxygen (flow 6 l/min) from canister transported on a wheeled cart.

We studied 34 pts (19 males, mean age 72±7 yrs, mean FEV1 1±0,4 l (41±12% pred.): 15 with RH (mean PaO2 52±4 mmHg) and 19 with EH (mean PaO2 66±4 mmHg). In 6 EH patients (32%) and in 10 RH patients (67%) 6MWD improved with O2 supplementation. In spite of significant improvement in SaO2 during tests with O2, neither dyspnea nor distance improved significantly in both groups. In RH 6MWD increased insignificantly by 13 m (295±110 m vs. 307±97 m) and in EH increased by only 2 m (356±94 m vs. 358±70 m). Despite the high O2 flow, 8 RH patients (53%) and 7 EH (37%) had SaO2 < 90% at the end of test. RH patients who desaturated had lower PaCO2 (44±6 vs. 53±6 mmHg, p<0.01). EH patients who desaturated covered longer 6MWD with (411±41 m vs. 326±65 m; p<0.01) and without oxygen (415±46 m vs. 322±99 m; p=0.03).

Oxygen supplementation from canister pulled on wheeled cart does not improve 6MWD; however, it may be more beneficial for exercise capacity in patients with RH than EH. Oxygen flow of 6 l/min does not protect against hypoxaemia during strenuous exercise.
Spontaneous cytotoxicity of rheumatoid and normal peripheral blood mononuclear cells against 4 human lymphoblastoid cell lines.
Authors: J Highton, G S Panayi
Journal: Annals of the Rheumatic Diseases (1980)

By measuring spontaneous cytotoxicity of unfractionated peripheral blood mononuclear cells from patients with rheumatoid arthritis and from normal individuals against 4 human lymphoblastoid cell lines we have been unable to demonstrate any preferential recognition of antigens on these cell lines by rheumatoid patients.
An Evolutionary Genome Scan for Longevity-Related Natural Selection in Mammals
Authors: R. W. Jobson, B. Nabholz, N. Galtier
Journal: Molecular Biology and Evolution (2009)

Aging is thought to occur through the accumulation of biochemical damage affecting DNA, proteins, and lipids. The major source of cellular damage involves the generation of reactive oxygen species produced during mitochondrial respiratory activity of the electron transport chain. Energetic metabolism, antioxidative processes, genome maintenance, and cell cycle are the cellular functions most commonly associated with aging, from experimental studies of model organisms. The significance of these experiments with respect to longevity-related selective constraints in nature remains unclear. Here we took a phylogenomic approach to identify the genetic targets of natural selection for elongated life span in mammals. By comparing the nonsynonymous and synonymous evolution of ∼5.7 million codon sites across 25 species, we identify codons and genes showing a stronger level of amino acid conservation in long-lived than in short-lived lineages. We show that genes involved in lipid composition and (collagen associated) vitamin C binding have collectively undergone increased selective pressure in long-lived species, whereas genes involved in DNA replication/repair or antioxidation have not. Most of the candidate genes experimentally associated with aging (e.g., PolG, Sod, Foxo) have played no detectable role in the evolution of longevity in mammals. A large body of current medical research aims at discovering how to increase longevity in human. In this study, we uncovered the way natural selection has completed this task during mammalian evolution. Cellular membrane and extracellular collagen composition, not genome integrity, have apparently been the optimized features.
Insulin receptor substrate-1 in osteoblast is indispensable for maintaining bone turnover
Authors: Naoshi Ogata, Daichi Chikazu, Naoto Kubota, Yasuo Terauchi, Kazuyuki Tobe, Yoshiaki Azuma, Tomohiro Ohta, Takashi Kadowaki, Kozo Nakamura, Hiroshi Kawaguchi
Journal: Journal of Clinical Investigation (2000)

Insulin receptor substrates (IRS-1 and -2) are essential for intracellular signaling by insulin and IGF-I, anabolic regulators of bone metabolism. Mice lacking the IRS-1 gene IRS-1(-/-) showed severe osteopenia with low bone turnover. IRS-1 was expressed in osteoblasts, but not in osteoclasts, of wild-type (WT) mice. IRS-1(-/-) osteoblasts treated with insulin or IGF-I failed to induce tyrosine phosphorylation of cellular proteins, and they showed reduced proliferation and differentiation. Osteoclastogenesis in the coculture of hemopoietic cells and osteoblasts depended on IRS-1 expression in osteoblasts and could not be rescued by IRS-1 expression in hemopoietic cells in the presence of not only IGF-I but also 1,25(OH)(2)D(3). In addition, osteoclast differentiation factor (RANKL/ODF) was not induced by these factors in IRS-1(-/-) osteoblasts. We conclude that IRS-1 deficiency in osteoblasts impairs osteoblast proliferation, differentiation, and support of osteoclastogenesis, resulting in low-turnover osteopenia. Osteoblastic IRS-1 is essential for maintaining bone turnover, because it mediates signaling by IGF-I and insulin and, we propose, also by other factors, such as 1,25(OH)(2)D(3).
Plasma low density lipoprotein transport kinetics in noninsulin-dependent diabetes mellitus.
Authors: A H Kissebah, S Alfarsi, D J Evans, P W Adams
Journal: Journal of Clinical Investigation (1983)

Plasma low density lipoprotein (LDL) transport kinetics were determined from the disappearance of 125I-LDL injected into age- and weight-matched groups of 13 normal subjects, 20 mild diabetics, and 8 moderately severe diabetic patients (fasting plasma glucose less than 150 and greater than 150 mg/100 ml, respectively). In mild diabetics, LDL apo-lipoprotein-B (apo-B) synthetic rate (SR) was significantly greater than normal. The fractional catabolic rate (FCR), however, was also increased so that plasma LDL concentration remained normal. In moderately severe diabetics, LDL SR was normal but FCR was reduced resulting in increased plasma LDL cholesterol and apo-B concentrations. In normal subjects, moderate obesity was associated with increased LDL secretion. In diabetic subjects, however, changes in LDL turnover were of equal magnitude in obese and nonobese patients. In normolipemic and hyperlipemic mild diabetic subjects with equal degrees of glucose intolerance, both LDL apo-B SR and FCR were greater than normal. The magnitude of these increases, however, was lower in the hyperlipemic individuals. Stepwise regression analysis revealed that both LDL SR and FCR correlated positively and linearly with insulin response to glucose loading, but negatively and curvilinearly with fasting plasma glucose and glucose response. We propose that in noninsulin-dependent diabetes, mild hyperglycemia is accompanied by increased LDL turnover, despite normal plasma LDL levels, whereas moderately severe hyperglycemia is associated with decreased LDL catabolism, resulting in increased plasma LDL levels. These changes cannot be attributed to the presence of obesity or hypertriglyceridemia, and may relate to varying degrees of insulin resistance and decreased insulin secretion affecting plasma very low density lipoprotein (VLDL) secretion, VLDL conversion to LDL, and LDL catabolism. Both increased LDL turnover in mild diabetes and delayed removal of LDL in moderately severe diabetes could increase cholesterol ester availability to peripheral tissues, and may result in an increased risk of atherosclerosis.
Use of a T-cell-based test for detection of tuberculosis infection among immunocompromised patients
Authors: F. Piana, L. R. Codecasa, P. Cavallerio, M. Ferrarese, G. B. Migliori, L. Barbarano, E. Morra, Daniela M. Cirillo
Journal: European Respiratory Journal (2006)

The aim of this study was to compare the performance of the T-SPOT.TB test, a T-cell-based test, with the tuberculin skin test (TST) in the diagnosis of latent tuberculosis (TB) infection. The study was carried out in 138 immunosuppressed haematology patients who had been nosocomially exposed to a case of smear-positive TB. Overall, 44.2% of the contacts were positive by T-SPOT.TB test, and 17.4% by TST (concordance 67.8%). The apparent prevalence of infection fell from 25.9 to 14.5% with the TST with increasing immunosuppression, although this difference was not significant. In contrast, the apparent prevalence of infection with the T-SPOT.TB test was unaffected at 44.6 and 44.3%, respectively. The T-SPOT.TB test had an overall indeterminate rate of 4.3%, and this was also unaffected by the level of immunosuppression. This study suggests that the T-SPOT.TB test maintains its sensitivity and performance in immunocompromised patients, identifying a large number of truly infected patients anergic to the tuberculin skin test.
Cytotoxic T-Lymphocyte–Associated Antigen-4 Single Nucleotide Polymorphisms and Haplotypes in Primary Biliary Cirrhosis
Authors: Peter Donaldson, Sivakumar Veeramani, Anna Baragiotta, Annarosa Floreani, Carla Venturi, Simon Pearce, Valerie Wilson, David Jones, Oliver James, John Taylor, Julia Newton, Margaret Bassendine
Journal: Clinical Gastroenterology and Hepatology (2007)
Efficacy and Safety of Rasburicase (recombinant urate oxidase) for the Prevention and Treatment of Hyperuricemia During Induction Chemotherapy of Aggressive Non-Hodgkin’s Lymphoma: Results of the GRAAL1 (Groupe d’Etude des Lymphomes de l’Adulte Trial on Rasburicase Activity in Adult Lymphoma) Study
Authors: Bertrand Coiffier, Nicolas Mounier, Serge Bologna, Christophe Fermé, Hervé Tilly, Anne Sonet, Bernard Christian, Olivier Casasnovas, Eric Jourdan, Karim Belhadj, Raoul Herbrecht
Journal: Journal of Clinical Oncology (2003)

Hyperuricemia and tumor lysis syndrome are well-known complications during induction treatment of aggressive non-Hodgkin's lymphomas (NHLs). Usual prophylaxis and treatment of hyperuricemia consist of hydration, alkalinization, and administration of allopurinol. This study was designed to evaluate the efficacy and the safety of rasburicase (recombinant urate oxidase) in adult patients with aggressive NHL during their first cycle of chemotherapy.A total of 100 patients from Groupe d'Etude des Lymphomes de l'Adulte centers, with diffuse large B-cell lymphoma (n = 79); anaplastic large-cell lymphoma (n = 6); peripheral T-cell lymphoma (n = 8); transformation of indolent lymphoma (n = 5); Burkitt's lymphoma (n = 1); and lymphoblastic lymphoma (n = 1) were enrolled from May 2001 to June 2002. Before chemotherapy, 66% of patients had elevated lactate dehydrogenase (LDH), including 28% with LDH above 1,000 U/mL. Eleven percent of patients were hyperuricemic (uric acid [UA] > 450 mmol/L or > 7.56 mg/dL). Rasburicase 0.20 mg/kg/d intravenously for 3 to 7 days was started the day before or at day 1 of chemotherapy. UA levels were measured 4 hours after rasburicase injection, then daily during treatment.All patients responded to rasburicase, as defined by normalization of UA levels maintained during chemotherapy. The control of UA was obtained within 4 hours after the first injection of the drug. Creatinine levels and other metabolites were also controlled with the administration of rasburicase. No patient exhibited increased creatinine levels or required dialysis during chemotherapy.Rasburicase is the treatment of choice to control UA and prevent tumor lysis syndrome in adult patients with aggressive NHL.
Detection of HHV-6-specific mRNA and antigens in PBMCs of individuals with chromosomally integrated HHV-6 (ciHHV-6)
Authors: V. Strenger, E. Caselli, I. Lautenschlager, W. Schwinger, S.W. Aberle, R. Loginov, V. Gentili, E. Nacheva, D. DiLuca, C. Urban
Journal: Clinical Microbiology and Infection (2014)
Radial probe endobronchial ultrasound for the diagnosis of peripheral lung cancer: systematic review and meta-analysis
Authors: D.P. Steinfort, Y.H. Khor, R.L. Manser, L.B. Irving
Journal: European Respiratory Journal (2010)

Improved diagnostic sensitivity of bronchsocopy for the investigation of peripheral pulmonary lesions (PPLs) with the use of radial probe endobroncial ultrasound (EBUS) has been reported, although diagnostic performance varies considerably. A systematic review of published literature evaluating radial probe EBUS accuracy was performed to determine point sensitivity and specificity, and to construct a summary receiver-operating characteristic curve. Sub-group analysis and linear regression was used to identify possible sources of study heterogeneity. 16 studies with 1,420 patients fulfilled inclusion criteria. Significant inter-study variation in EBUS method was noted. EBUS had point specificity of 1.00 (95% CI 0.99-1.00) and point sensitivity of 0.73 (95% CI 0.70-0.76) for the detection of lung cancer, with a positive likelihood ratio of 26.84 (12.60-57.20) and a negative likelihood ratio of 0.28 (0.23-0.36). Significant inter-study heterogeneity for sensitivity was observed, with prevalence of malignancy, lesion size and reference standard used being possible sources. EBUS is a safe and relatively accurate tool in the investigation of PPLs. Diagnostic sensitivity of EBUS may be influenced by the prevalence of malignancy in the patient cohort being examined and lesion size. Further methodologically rigorous studies on well-defined patient populations are required to evaluate the generalisability of our results.
Cancer-Related Direct-to-Consumer Advertising: Awareness, Perceptions, and Reported Impact Among Patients Undergoing Active Cancer Treatment
Authors: Gregory A. Abel, Harold J. Burstein, Nathanael D. Hevelone, Jane C. Weeks
Journal: Journal of Clinical Oncology (2009)

Although cancer-related direct-to-consumer advertising (CR-DTCA) is prevalent, little is known about cancer patients' experiences with this controversial medium of medical communication.We administered a 41-item, mailed questionnaire to consecutive patients with breast and hematologic malignancies who were undergoing active treatment at our institution. We assessed awareness of CR-DTCA within the prior year, perceptions of CR-DTCA, and CR-DTCA-prompted patient and provider behaviors.We received 348 completed questionnaires (response rate, 75.0%). Overall, 86.2% reported being aware of CR-DTCA, most frequently from television (77.7%). Awareness did not vary with clinical or sociodemographic factors except that patients were more likely to be aware of CR-DTCA for products specific to their cancer types (P < .0001). A majority of those aware reported that CR-DTCA made them "aware of treatments they did not know about" (62.2%), provided information in "a balanced manner" (65.2%), and helped them to have "better discussions" with their provider (56.8%). These perceptions were significantly more favorable among those who had not graduated from college (P < .05 for each). Overall, 11.2% reported that CR-DTCA made them "less confident" in their providers' judgment. Of those aware, 17.3% reported talking to their provider about an advertised medication, although less than one fifth of those reported receiving a prescription for the advertised medication.The patients in our cohort were highly aware of CR-DTCA. CR-DTCA was found to be accessible and useful; however, it decreased some patients' confidence in their providers' judgment. CR-DTCA prompted a modest amount of patient-provider discussion but infrequent patient-reported changes in therapy.
Intensive insulin therapy protects the endothelium of critically ill patients
Authors: L. Langouche
Journal: Journal of Clinical Investigation (2005)

The vascular endothelium controls vasomotor tone and microvascular flow and regulates trafficking of nutrients and biologically active molecules. When endothelial activation is excessive, compromised microcirculation and subsequent cellular hypoxia contribute to the risk of organ failure. We hypothesized that strict blood glucose control with insulin during critical illness protects the endothelium, mediating prevention of organ failure and death. In this preplanned subanalysis of a large, randomized controlled study, intensive insulin therapy lowered circulating levels of ICAM-1 and tended to reduce E-selectin levels in patients with prolonged critical illness, which reflects reduced endothelial activation. This effect was not brought about by altered levels of endothelial stimuli, such as cytokines or VEGF, or by upregulation of eNOS. In contrast, prevention of hyperglycemia by intensive insulin therapy suppressed iNOS gene expression in postmortem liver and skeletal muscle, possibly in part via reduced NF-κB activation, and lowered the elevated circulating NO levels in both survivors and nonsurvivors. These effects on the endothelium statistically explained a significant part of the improved patient outcome with intensive insulin therapy. In conclusion, maintaining normoglycemia with intensive insulin therapy during critical illness protects the endothelium, likely in part via inhibition of excessive iNOS-induced NO release, and thereby contributes to prevention of organ failure and death.
Stellate ganglion block for the management of hot flashes and sleep disturbances in breast cancer survivors: an uncontrolled experimental study with 24 weeks of follow-up
Authors: K. Haest, A. Kumar, B. Van Calster, K. Leunen, A. Smeets, F. Amant, P. Berteloot, H. Wildiers, R. Paridaens, E. Van Limbergen, C. Weltens, H. Janssen, S. Peeters, J. Menten, I. Vergote, B. Morlion, J. Verhaeghe, M.R. Christiaens, P. Neven
Journal: Annals of Oncology (2011)
Blockade of interleukin 6 trans signaling suppresses T-cell resistance against apoptosis in chronic intestinal inflammation: Evidence in Crohn disease and experimental colitis in vivo
Authors: R. Atreya, J. Mudter, S. Finotto, J. Müllberg, T. Jostock, S. Wirtz, M. Schütz, B. Bartsch, M. Holtmann, C. Becker, D. Strand, J. Czaja, J. F. Schlaak, H.A. Lehr, F. Autschbach, G. Schürmann, N. Nishimoto, K. Yoshizaki, H. Ito, T. Kishimoto, P.R. Galle, S. Rose-John, M.F. Neurath
Journal: Nature Medicine (2000)
Ubiquitin Ligases and the Immune Response
Authors: Yun-Cai Liu
Journal: Annual Review of Immunology (2004)

Ubiquitin (Ub)-protein conjugation represents a novel means of posttranscriptional modification in a proteolysis-dependent or -independent manner. E3 Ub ligases play a key role in governing the cascade of Ub transfer reactions by recognizing and catalyzing Ub conjugation to specific protein substrates. The E3s, which can be generally classified into HECT-type and RING-type families, are involved in the regulation of many aspects of the immune system, including the development, activation, and differentiation of lymphocytes, T cell-tolerance induction, antigen presentation, immune evasion, and virus budding. E3-promoted ubiquitination affects a wide array of biological processes, such as receptor downmodulation, signal transduction, protein processing or translocation, protein-protein interaction, and gene transcription, in addition to proteasome-mediated degradation. Deficiency or mutation of some of the E3s like Cbl, Cbl-b, or Itch, causes abnormal immune responses such as autoimmunity, malignancy, and inflammation. This review discusses our current understanding of E3 Ub ligases in both innate and adaptive immunity. Such knowledge may facilitate the development of novel therapeutic approaches for immunological diseases.
Specific Histone Patterns and Acetylase/Deacetylase Activity at the Breakpoint-Cluster Region of the Human <b> <i>MLL</i> </b> Gene
Authors: Andriy Khobta, Carmelo Carlo-Stella, Giovanni Capranico
Journal: Cancer Research (2004)

Abstract The MLL gene breakpoint-cluster region (BCR) is a known hot-spot for chromosomal translocations in human leukemias. We mapped core histone modifications and histone H1 along the MLL gene in Jurkat cells and human CD34+ progenitor blood cells by chromatin immunoprecipitation. Within the BCR, we found specific histone patterns that were different from other genomic regions and a histone H1-free fragment at the telomeric end. Core histone acetylase/deacetylase activities were also found within the BCR. In the studied cell models, chromatin components at the MLL BCR suggest an asymmetric organization that may influence early molecular events eventually leading to chromosomal translocations.